Mitochondrial metabolic states and membrane potential modulate mtNOS activity

AbstractThe mitochondrial metabolic state regulates the rate of NO release from coupled mitochondria: NO release by heart, liver and kidney mitochondria was about 40–45% lower in state 3 (1.2, 0.7 and 0.4 nmol/min mg protein) than in state 4 (2.2, 1.3 and 0.7 nmol/min mg protein). The activity of mtNOS, responsible for NO release, appears driven by the membrane potential component and not by intramitochondrial pH of the proton motive force. The intramitochondrial concentrations of the NOS substrates, l-arginine (about 310 μM) and NADPH (1.04–1.78 mM) are 60–1000 times higher than their KM values. Moreover, the changes in their concentrations in the state 4–state 3 transition are not enough to explain the changes in NO release. Nitric oxide release was exponentially dependent on membrane potential as reported for mitochondrial H2O2 production [S.S. Korshunov, V.P. Skulachev, A.A. Satarkov, High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria. FEBS Lett. 416 (1997) 15–18.]. Agents that decrease or abolish membrane potential minimize NO release while the addition of oligomycin that produces mitochondrial hyperpolarization generates the maximal NO release. The regulation of mtNOS activity, an apparently voltage-dependent enzyme, by membrane potential is marked at the physiological range of membrane potentials

How to stay together? Habitat use by three sympatric sharks in the western coast of Baja California Sur, Mexico

Sharks are top predators and play an important role in the regulation of marine ecosystems at lower trophic position. Mustelus californicus, Sphyrna zygaena, and Isurus oxyrinchus prove to be important fishery resources along the western coast of Baja California Sur and cohabit the same coastal areas, probably sharing resources. However, our knowledge about ecological dynamics of multiple species coexisting and sharing similar habitat resources is still limited, particularly for predators such as sharks. Therefore, this study focuses on the analysis of trophic ecology of the sharks species, using carbon (C) and nitrogen (N) stable isotope values in muscle tissues coupled with trace element concentration (Hg, Se, and Cd) in muscle and hepatic tissues of sharks. The values of δC (M. californicus −17.3 ± 1.1‰, S. zygaena −17.9 ± 0.5‰, and I. oxyrinchus −18.3 ± 0.3‰) and δN (M. californicus 18.2 ± 1.1‰, S. zygaena 18.4 ± 0.9‰, and I. oxyrinchus 17.8 ± 1.1‰) indicated that these species feed in the Gulf of Ulloa all throughout the year, and for extended periods with similar habitat use and trophic niche. The above-mentioned statement is also a conclusion supported by the significant correlation between isotopic and trace element concentrations in the muscular tissues in all studied species. Thus, the results of the present study emphasize the habitat and niche characteristics of three sympatric sharks off the coast of Baja California Sur, Mexico.The Instituto Politecnico Nacional (COFFA, EDI), CONA-CYT project 25370, Instituto Politecnico Nacional grants 20181417 and 20196736 and SIP20211002 and SIP2152 provided the fellowships to support this study

Analysis and optimization of the virtual teaching practice of Applied Physicochemistry

Se analiza la estrategia empleada para el dictado virtual de la asignatura Fisicoquímica Aplicada de la Carrera de Especialización en Esterilización para Farmacéuticos. Se describe el programa de actividades desarrollado puntualizando las Fortalezas/Debilidades y Oportunidades/Amenazas del empleo del Aula Virtual, comparando las observaciones de docentes y alumnos en varias cohortes. Se proponen acciones a implementarse con el objetivo de enriquecer el dictado de la asignatura.Universidad de Buenos AiresInstituto de Fisiología Vegeta

Clofarabine ± Fludarabine with Once Daily i.v. Busulfan as Pretransplant Conditioning Therapy for Advanced Myeloid Leukemia and MDS

Although a combination of i.v. busulfan (Bu) and fludarabine (Flu) is a safe, reduced-toxicity conditioning program for acute myelogenous leukemia/myelodysplastic syndromes (AML/MDS), recurrent leukemia posttransplantation remains a problem. To enhance the conditioning regimen’s antileukemic effect, we decided to supplant Flu with clofarabine (Clo), and assayed the interactions of these nucleoside analogs alone and in combination with Bu in Bu-resistant human cell lines in vitro. We found pronounced synergy between each nucleoside and the alkylator but even more enhanced cytotoxic synergy when the nucleoside analogs were combined prior to exposing the cells to Bu. We then designed a 4-arm clinical trial in patients with myeloid leukemia undergoing allogeneic stem cell transplantation (allo-SCT). Patients were adaptively randomized as follows: Arm I–Clo:Flu 10:30 mg/m2, Arm II—20:20 mg/m2, Arm III—30:10 mg/m2, and Arm IV–single-agent Clo at 40 mg/m2. The nucleoside analog(s) were/was infused over 1 hour once daily for 4 days, followed on each day by Bu, infused over 3 hours to a pharmacokinetically targeted daily area under the curve (AUC) of 6000 μMol-min ± 10%. Fifty-one patients have been enrolled with a minimum follow-up exceeding 100 days. There were 32 males and 19 females, with a median age of 45 years (range: 6-59). Nine patients had chronic myeloid leukemia (CML) (BC: 2, second AP: 3, and tyrosine-kinase inhibitor refractory first chronic phase [CP]: 4). Forty-two patients had AML: 14 were induction failures, 8 in first chemotherapy-refractory relapse, 7 in untreated relapse, 3 in second or subsequent relapse, 4 were in second complete remission (CR), and 3 in second CR without platelet recovery (CRp), 2 were in high-risk CR1. Finally, 1 patient was in first CRp. Graft-versus-host disease (GVHD) prophylaxis was tacrolimus and mini-methorexate (MTX), and those who had an unrelated or 1 antigen-mismatched donor received low-dose rabbit-ATG (Thymoglobulin™). All patients engrafted. Forty-one patients had active leukemia at the time of transplant, and 35 achieved CR (85%). Twenty of the 42 AML patients and 5 of 9 CML patients are alive with a projected median overall survival (OS) of 23 months. Marrow and blood (T cell) chimerism studies at day +100 revealed that both in the lower-dose Clo groups (groups 1+2) and the higher-dose Clo groups (groups 3+4), the patients had a median of 100% donor (T cell)-derived DNA. There has been no secondary graft failure. In the first 100 days, 1 patient died of pneumonia, and 1 of liver GVHD. We conclude that (1) Clo ± Flu with i.v. Bu as pretransplant conditioning is safe in high-risk myeloid leukemia patients; (2) clofarabine is sufficiently immunosuppressive to support allo-SCT in myeloid leukemia; and (3) the median OS of 23 months in this high-risk patient population is encouraging. Additional studies to evaluate the antileukemic efficacy of Clo ± Flu with i.v. Bu as pretransplant conditioning therapy are warranted

Nuevas socialidades, y configuraciones de mundo entorno a las redes sociales digitales. Un estudio situado con jóvenes estudiantes

Ulla, Cecilia. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Emanuelli, Paulina B. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Ardini, Claudia. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Vargas, Laura. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Ortúzar, Isabel. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Redolfi, Cecilia. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Masera, Marta. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Trimano, Luciana. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Zárate, Zulma. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Calderón, Angelina. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Rey, Mariana. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Ferrari, Mariana. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Massetti, Carolina. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Manzanares, Belén. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Altieri, Ana Clara. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Moroni, Luciano. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Valdez, Lucas. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Moreno, Soledad. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Ulla, Cecilia. Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Vivimos en la denominada revolución virtual donde los procesos comunicativos son mediados por tecnologías digitales. En una nueva forma de intercambio simbólico y construcción de relaciones interpersonales dentro de un grupo específico, la juventud, que va a constituir un nuevo mundo compartido y construido por sus miembros en base a las representaciones sociales e imaginarios colectivos, con fuerte implicaciones intersubjetivas. Así las Tribus Urbanas a modo de expresión y alejamiento de la monotonía de lo institucionalizado, van a ser representantes de un nuevo espíritu del tiempo que se puede llamar con el nombre de socialidad. En éste marco nos interrogamos: ¿Qué cosmovisión tienen los jóvenes de ingresantes a primer año de la Escuela de Ciencias de la Información, del espacio, tiempo, territorio, relaciones, emociones, del trabajo y los Valores hegemónicos?Ulla, Cecilia. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Emanuelli, Paulina B. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Ardini, Claudia. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Vargas, Laura. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Ortúzar, Isabel. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Redolfi, Cecilia. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Masera, Marta. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Trimano, Luciana. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Zárate, Zulma. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Calderón, Angelina. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Rey, Mariana. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Ferrari, Mariana. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Massetti, Carolina. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Manzanares, Belén. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Altieri, Ana Clara. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Moroni, Luciano. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Valdez, Lucas. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Moreno, Soledad. (2013). Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Ulla, Cecilia. Universidad Nacional de Córdoba. Escuela de Ciencias de la Información. Argentina.Otras Comunicación y Medio

Within-Host Dynamics of the Hepatitis C Virus Quasispecies Population in HIV-1/HCV Coinfected Patients

HIV/HCV coinfected individuals under highly active antiretroviral therapy (HAART) represent an interesting model for the investigation of the role played by the immune system in driving the evolution of the HCV quasispecies. We prospectively studied the intra-host evolution of the HCV heterogeneity in 8 coinfected subjects, selected from a cohort of 32 patients initiating HAART: 5 immunological responders (group A) and 3 immunological non-responders (group B), and in two HCV singly infected controls not assuming drugs (group C). For all these subjects at least two serial samples obtained at the first observation (before HAART) and more than 1 year later, underwent clonal sequence analysis of partial E1/E2 sequences, encompassing the whole HVR1. Evolutionary rates, dated phylogenies and population dynamics were co-estimated by using a Bayesian Markov Chain Monte Carlo approach, and site specific selection pressures were estimated by maximum likelihood-based methods. The intra-host evolutionary rates of HCV quasispecies was 10 times higher in subjects treated with HAART than in controls without immunodeficiency (1.9 and 2.3×10−3 sub/site/month in group A and B and 0.29×10−3 sub/site/month in group C individuals). The within-host Bayesian Skyline plot analysis showed an exponential growth of the quasispecies populations in immunological responders, coinciding with a peak in CD4 cell counts. On the contrary, quasispecies population remained constant in group B and in group C controls. A significant positive selection pressure was detected in a half of the patients under HAART and in none of the group C controls. Several sites under significant positive selection were described, mainly included in the HVR1. Our data indicate that different forces, in addition to the selection pressure, drive an exceptionally fast evolution of HCV during HAART immune restoration. We hypothesize that an important role is played by the enlargement of the viral replicative space

Gut Microbiome Dysbiosis in Antibiotic-Treated COVID-19 Patients is Associated with Microbial Translocation and Bacteremia

Although microbial populations in the gut microbiome are associated with COVID-19 severity, a causal impact on patient health has not been established. Here we provide evidence that gut microbiome dysbiosis is associated with translocation of bacteria into the blood during COVID-19, causing life-threatening secondary infections. We first demonstrate SARS-CoV-2 infection induces gut microbiome dysbiosis in mice, which correlated with alterations to Paneth cells and goblet cells, and markers of barrier permeability. Samples collected from 96 COVID-19 patients at two different clinical sites also revealed substantial gut microbiome dysbiosis, including blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species. Analysis of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data indicates that bacteria may translocate from the gut into the systemic circulation of COVID-19 patients. These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension

Aims Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk