Publications by authors named "Alan Briones"

10 Publications

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Activation of regulator ArcA in the presence of hypochlorite in Salmonella enterica serovar Typhimurium.

Biochimie 2021 Jan 12;180:178-185. Epub 2020 Nov 12.

Laboratorio de Microbiología Molecular, Millennium Institute on Immunology and Immunotherapy, Departamento de Ciencias de la Vida, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, Chile. Electronic address:

Oxidative stress is the main mechanism behind efficient disinfectants, causing damage in bacterial macromolecules. Importantly, bacteria activate resistance mechanisms in response to damage generated by oxidative stress. Strategies allowing pathogens to survive oxidative stress are highly conserved among microorganisms. Many of these strategies entail genomic responses triggered by signals transduced through Two Component Systems (TCS). Recently, we demonstrated that the TCS ArcAB (specifically ArcA) participates in bacterial responses to hypochlorite, regulating the uptake of this toxic compound and being involved in resistance and survival inside neutrophils, where hypochlorous acid abounds. Here, we demonstrated that ArcA is required in the response to oxidative stress generated by hypochlorite, independent of its cognate sensor ArcB or the Asp54 of ArcA, the only phosphorylable residue in ArcA, which is required to function as a gene regulator. Our results suggest that ArcA could have additional functions to respond to oxidative stress, independent of its regulatory activity, which might require interaction with other unknown relevant proteins.
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http://dx.doi.org/10.1016/j.biochi.2020.11.009DOI Listing
January 2021

An Integral Pedagogical Strategy for Teaching and Learning IoT Cybersecurity.

Sensors (Basel) 2020 Jul 17;20(14). Epub 2020 Jul 17.

Engineering Department, Universitat Ramon Llull (URL), La Salle, 08022 Barcelona, Spain.

Internet of Things (IoT) has become a fundamental content of any engineering program due to the emerging need of experts in this field. However, the complexity of technologies that interact in IoT environments and the amount of different professional profiles required to design, implement and manage IoT environments, considering cybersecurity as a must, has led to a huge challenge in the educational world. This paper proposes an integral pedagogical strategy for learning IoT cybersecurity structured in three different stages, in a higher education institution. These stages focus not only on the content about IoT and cybersecurity but also on the competencies to acquire, the most suitable learning methodologies and the expected learning outcomes. The association of these concepts in each stage is detailed. Examples of courses are explained, the related competencies and learning outcomes are specified, and the contents and methodologies to achieve the expected results are described. An analysis of student results and stakeholder evaluations is provided to verify if the pedagogical strategy proposed is suitable. Furthermore, students' feedback is included to corroborate the innovation, the suitability of the acquired skills, and the overall student satisfaction with the related courses and consequently with the proposed IoT cybersecurity pedagogical strategy.
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http://dx.doi.org/10.3390/s20143970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411857PMC
July 2020

The Transcription Factor ArcA Modulates 's Metabolism in Response to Neutrophil Hypochlorous Acid-Mediated Stress.

Front Microbiol 2019 5;10:2754. Epub 2019 Dec 5.

Laboratorio de Microbiología Molecular, Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, Chile.

Typhimurium, a bacterial pathogen with high metabolic plasticity, can adapt to different environmental conditions; these traits enhance its virulence by enabling bacterial survival. Neutrophils play important roles in the innate immune response, including the production of microbicidal reactive oxygen species (ROS). In addition, the myeloperoxidase in neutrophils catalyzes the formation of hypochlorous acid (HOCl), a highly toxic molecule that reacts with essential biomolecules, causing oxidative damage including lipid peroxidation and protein carbonylation. The bacterial response regulator ArcA regulates adaptive responses to oxygen levels and influences the survival of inside phagocytic cells. Here, we demonstrate by whole transcriptomic analyses that ArcA regulates genes related to various metabolic pathways, enabling bacterial survival during HOCl-stress . Also, inside neutrophils, ArcA controls the transcription of several metabolic pathways by downregulating the expression of genes related to fatty acid degradation, lysine degradation, and arginine, proline, pyruvate, and propanoate metabolism. ArcA also upregulates genes encoding components of the oxidative pathway. These results underscore the importance of ArcA in ATP generation inside the neutrophil phagosome and its participation in bacterial metabolic adaptations during HOCl stress.
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http://dx.doi.org/10.3389/fmicb.2019.02754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906141PMC
December 2019

Arsenic Response of Three Altiplanic Strains With Different Tolerance Levels Against the Metalloid Species: A Proteomics Study.

Front Microbiol 2019 26;10:2161. Epub 2019 Sep 26.

Laboratorio de Microbiología Molecular, Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, Chile.

is a polyextremophile bacterial genus with a physiology that allows it to develop in different adverse environments. The Salar de Huasco is one of these environments due to its altitude, atmospheric pressure, solar radiation, temperature variations, pH, salinity, and the presence of toxic compounds such as arsenic. However, the physiological and/or molecular mechanisms that enable them to prosper in these environments have not yet been described. Our research group has isolated several strains of genus from different sites of Salar de Huasco, which show different resistance levels to As(III) and As(V). In this work, we compare the protein expression patterns of the three strains in response to arsenic by a proteomic approach; strains were grown in absence of the metalloid and in presence of As(III) and As(V) sublethal concentrations and the protein separation was carried out in 2D electrophoresis gels (2D-GE). In total, 999 spots were detected, between 77 and 173 of which showed significant changes for As(III) among the three strains, and between 90 and 143 for As(V), respectively, compared to the corresponding control condition. Twenty-seven of those were identified by mass spectrometry (MS). Among these identified proteins, the ArsA [ATPase from the As(III) efflux pump] was found to be up-regulated in response to both arsenic conditions in the three strains, as well as the Co-enzyme A disulfide reductase (Cdr) in the two more resistant strains. Interestingly, in this genus the gene that codifies for Cdr is found within the genic context of the operon. We suggest that this protein could be restoring antioxidants molecules, necessary for the As(V) reduction. Additionally, among the proteins that change their expression against As, we found several with functions relevant to stress response, e.g., Hpf, LuxS, GLpX, GlnE, and Fur. This study allowed us to shed light into the physiology necessary for these bacteria to be able to tolerate the toxicity and stress generated by the presence of arsenic in their niche.
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http://dx.doi.org/10.3389/fmicb.2019.02161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775490PMC
September 2019

The ArcAB two-component regulatory system promotes resistance to reactive oxygen species and systemic infection by Salmonella Typhimurium.

PLoS One 2018 4;13(9):e0203497. Epub 2018 Sep 4.

Laboratorio de Microbiología Molecular, Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, Chile.

Salmonella enterica Serovar Typhimurium (S. Typhimurium) is an intracellular bacterium that overcomes host immune system barriers for successful infection. The bacterium colonizes the proximal small intestine, penetrates the epithelial layer, and is engulfed by macrophages and neutrophils. Intracellularly, S. Typhimurium encounters highly toxic reactive oxygen species including hydrogen peroxide and hypochlorous acid. The molecular mechanisms of Salmonella resistance to intracellular oxidative stress is not completely understood. The ArcAB two-component system is a global regulatory system that responds to oxygen. In this work, we show that the ArcA response regulator participates in Salmonella adaptation to changing oxygen levels and is also involved in promoting intracellular survival in macrophages and neutrophils, enabling S. Typhimurium to successfully establish a systemic infection.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203497PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122832PMC
February 2019

The transcription factor SlyA from Salmonella Typhimurium regulates genes in response to hydrogen peroxide and sodium hypochlorite.

Res Microbiol 2018 Jul - Aug;169(6):263-278. Epub 2018 May 29.

Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Laboratorio de Microbiología Molecular, Universidad Nacional Andrés Bello, Santiago, Chile; Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Millennium Institute on Immunology and Immunotherapy, Universidad Nacional Andrés Bello, Santiago, Chile. Electronic address:

Salmonella Typhimurium is an intracellular pathogen that is capable of generating systemic fever in a murine model. Over the course of the infection, Salmonella faces different kinds of stressors, including harmful reactive oxygen species (ROS). Various defence mechanisms enable Salmonella to successfully complete the infective process in the presence of such stressors. The transcriptional factor SlyA is involved in the oxidative stress response and invasion of murine macrophages. We evaluated the role of SlyA in response to HO and NaOCl and found an increase of slyA expression upon exposure to these toxics. However, the SlyA target genes and the molecular mechanisms by which they influence the infective process are unknown. We hypothesised that SlyA regulates the expression of genes required for ROS resistance, metabolism, or virulence under oxidative stress conditions. Transcriptional profiling in wild type and ΔslyA strains confirmed that SlyA regulates the expression of several genes involved in virulence [sopD (STM14_3550), sopE2 (STM14_2244), hilA (STM14_3475)] and central metabolism [kgtP (STM14_3252), fruK (STM14_2722), glpA (STM14_2819)] in response to HO and NaOCl. These findings were corroborated by functional assay and transcriptional fusion assays using GFP. DNA-protein interaction assays showed that SlyA regulates these genes through direct interaction with their promoter regions.
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http://dx.doi.org/10.1016/j.resmic.2018.04.003DOI Listing
October 2018

Hospitalist-vascular surgery comanagement: effects on complications and mortality.

Hosp Pract (1995) 2016 Dec 24;44(5):233-236. Epub 2016 Nov 24.

a Division of Hospital Medicine , The Mount Sinai Hospital , New York , NY , USA.

Objectives: Hospitalized vascular surgery patients have multiple severe comorbidities, poor functional status, and high perioperative cardiac risk. Thus they may be ideal patients for a collaborative care model. However, there is little evidence for a comanagement model on clinical outcomes.

Methods: The two-year pre-post study consisted of a comanagement model where a hospitalist actively participated in the medical care of American Society of Anesthesiologist Physical Status Classification scale 3 or 4 vascular surgery patients. Outcomes were in-hospital mortality, length of stay, 30-day readmission rate, pain scores, and patient safety metrics.

Results: With comanagement, patient complications decreased from 3.5 to 2.2 events per 1000 patients. (p = 0.045). Mortality decreased from 2.01% to 1.00% (p = 0.049), corresponding to a decrease in the risk-adjusted observed to expected mortality rate ratio from 1.22 to 0.53 (p = 0.01). Patient reported pain scores improved; more patients in the comanagement cohort expressed no pain (72% vs 82.8%; p = 0.01) and there were reductions in reports of mild and moderate pain. There was no significant difference in the risk-adjusted length of stay (observed to expected ratio 0.83 to 0.88 for the pre-intervention and comanagement groups, respectively, p = 0.48). The 30-day readmission rate was unchanged (21.9 vs 20.6% p = 0.44). Patients in the intervention period were more clinically complex, as evidenced by the greater case mix index (2.21 vs 2.44).

Conclusions: After two years of implementation, our comanagement service reduced complications, mortality, and pain scores among high-risk vascular surgery patients.
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http://dx.doi.org/10.1080/21548331.2016.1259543DOI Listing
December 2016

The effect of a hospitalist comanagement service on vascular surgery inpatients.

J Vasc Surg 2015 Jun 19;61(6):1550-5. Epub 2015 Feb 19.

Division of Hospitalist Medicine, Department of Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY.

Objective: Vascular surgery patients have increased medical comorbidities that amplify the complexity of their care. We assessed the effect of a hospitalist comanagement service on inpatient vascular surgery outcomes.

Methods: We divided 1059 patients into two cohorts for comparison: 515 between January 2012 and December 2012, before the implementation of a hospitalist comanagement service, and 544 between January 2013 and October 2013, after the initiation of a hospitalist comanagement service. Nine vascular surgeons and 10 hospitalists participated in the hospitalist comanagement service. End points measured were in-hospital mortality, length of stay (LOS), 30-day readmission rates, visual analog scale pain scores (0-10), inpatient adult safety assessments using the Agency for Healthcare Research and Quality (AHRQ) Patient Safety Indicators, and resident perceptions assessed by survey.

Results: The in-hospital mortality rate decreased from 1.75% to 0.37% after the implementation of the hospitalist comanagement service (P = .016), with a decrease in the observed-to-expected ratio from 0.89 to 0.22. The risk-adjusted in-hospital mortality decreased from 1.56% to 0.0008% (P = .003). Mean LOS was lower in the base period, at 5.1 days vs 5.5 days (P < .001), with an observed-to-expected ratio of 0.83 and 0.78, respectively. The risk-adjusted LOS increased from 4.2 days to 4.3 days (P < .001). The overall 30-day readmission rate was unchanged, at 23.1% compared with 22.8% (P = .6). The related 30-day readmission rate was also similar, at 11.5% compared with 11.4% (P = .5). Patients reporting no pain during hospitalization increased from 72.8% before the hospitalist comanagement service to 77.8% after (P = .04). Reports of moderate pain decreased from 14% to 9.6% (P = .016). Mild and severe pain scores were similar between the two groups. Adult safety measured by AHRQ demonstrated a decrease from three to zero patients in the number of deaths among surgical patients with treatable complications (P = .04). Most house staff reported that the comanagement program had a positive effect on patient care and education.

Conclusions: The hospitalist comanagement service has resulted in a significant decrease in in-hospital mortality rates, patient safety, as measured by AHRQ, and improved pain scores. Resident surveys demonstrated perceived improvement in patient care and education. Continued observation will be necessary to assess the long-term effect of the hospitalist comanagement service on quality metrics.
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http://dx.doi.org/10.1016/j.jvs.2015.01.006DOI Listing
June 2015

A model of a hospitalist role in the care of admitted patients in the emergency department.

J Hosp Med 2010 Jul-Aug;5(6):360-4

Department of Medicine, Mount Sinai Medical Center, New York, New York, USA.

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http://dx.doi.org/10.1002/jhm.636DOI Listing
January 2011
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