Modulation of sulfur metabolism enables efficient glucosinolate engineering

<p>Abstract</p> <p>Background</p> <p>Metabolic engineering in heterologous organisms is an attractive approach to achieve efficient production of valuable natural products. Glucosinolates represent a good example of such compounds as they are thought to be the cancer-preventive agents in cruciferous plants. We have recently demonstrated that it is feasible to engineer benzylglucosinolate (BGLS) in the non-cruciferous plant <it>Nicotiana benthamiana </it>by transient expression of five genes from <it>Arabidopsis thaliana</it>. In the same study, we showed that co-expression of a sixth <it>Arabidopsis </it>gene, <it>γ-glutamyl peptidase 1 </it>(<it>GGP1</it>), resolved a metabolic bottleneck, thereby increasing BGLS accumulation. However, the accumulation did not reach the expected levels, leaving room for further optimization.</p> <p>Results</p> <p>To optimize heterologous glucosinolate production, we have in this study performed a comparative metabolite analysis of BGLS-producing <it>N. benthamiana </it>leaves in the presence or absence of <it>GGP1</it>. The analysis revealed that the increased BGLS levels in the presence of <it>GGP1 </it>were accompanied by a high accumulation of the last intermediate, desulfoBGLS, and a derivative thereof. This evidenced a bottleneck in the last step of the pathway, the transfer of sulfate from 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to desulfoBGLS by the sulfotransferase AtSOT16. While substitution of AtSOT16 with alternative sulfotransferases did not alleviate the bottleneck, experiments with the three genes involved in the formation and recycling of PAPS showed that co-expression of <it>adenosine 5'-phosphosulfate kinase 2 </it>(<it>APK2</it>) alone reduced the accumulation of desulfoBGLS and its derivative by more than 98% and increased BGLS accumulation 16-fold.</p> <p>Conclusion</p> <p>Adjusting sulfur metabolism by directing sulfur from primary to secondary metabolism leads to a remarkable improvement in BGLS accumulation and thereby represents an important step towards a clean and efficient production of glucosinolates in heterologous hosts. Our study emphasizes the importance of considering co-substrates and their biological nature in metabolic engineering projects.</p

Interventional Techniques for Head and Neck Cancer Pain

One of the most feared consequences of cancer is the possibility of severe and uncontrolled pain in patients with advanced cancer. Patients with head and neck cancer (HNC) have the highest prevalence of pain among patients with cancer,and it is often one of the major reasons for seeking care. A subspecialty approach that incorporates anatomical and technical knowledge to alleviate pain through minimally invasive procedures is relatively recent. The purpose of this chapter is to present different interventional techniques which are used for the treatment of pain in HNC patients when drug treatment is unsuccessful

Edoxaban Versus Low-Molecular-Weight Heparin in Hospitalized COVID-19 Patients With Atrial Fibrillation

COVID-19; Atrial fibrillation; EdoxabanCOVID-19; Fibrilación auricular; EdoxabanCOVID-19; Fibril·lació auricular; EdoxabanObjective During the first wave of the SARS-CoV-2 pandemic, management of anticoagulation therapy in hospitalized patients with atrial fibrillation (AF) was simplified to low-molecular-weight heparin (LMWH) followed by oral anticoagulation, mainly owing to the risk of drug–drug interactions. However, not all oral anticoagulants carry the same risk. Methods Observational, retrospective, and multicenter study that consecutively included hospitalized patients with AF anticoagulated with LMWH followed by oral anticoagulation or edoxaban concomitantly with empirical COVID-19 therapy. Time-to-event (mortality, total bleeds, and admissions to ICU) curves, using an unadjusted Kaplan-Meier method and Cox regression model adjusted for potential confounders were constructed. Results A total of 232 patients were included (80.3 ± 7.7 years, 50.0% men, CHA2DS2-VASc 4.1 ± 1.4; HAS-BLED 2.6 ± 1.0). During hospitalization, patients were taking azithromycin (98.7%), hydroxychloroquine (89.7%), and ritonavir/lopinavir (81.5%). The mean length of hospital stay was 14.6 ± 7.2 days, and total follow-up was 31.6 ± 13.4 days; 12.9% of patients required admission to ICU, 18.5% died, and 9.9% had a bleeding complication (34.8% major bleeding). Length of hospital stay was longer in patients taking LMWH (16.0 ± 7.7 vs 13.3 ± 6.5 days; P = .005), but mortality and total bleeds were similar in patients treated with edoxaban and those treated with LMWH followed by oral anticoagulation. Conclusions Mortality rates, arterial and venous thromboembolic complications, and bleeds did not significantly differ between AF patients receiving anticoagulation therapy with edoxaban or LMWH followed by oral anticoagulation. However, the duration of hospitalization was significantly lower with edoxaban. Edoxaban had a similar therapeutic profile to LMWH followed by oral anticoagulation and may provide additional benefits

Static friction between rigid fractal surfaces

Using spheropolygon-based simulations and contact slope analysis, we investigate the effects of surface topography and atomic scale friction on the macroscopically observed friction between rigid blocks with fractal surface structures. From our mathematical derivation, the angle of macroscopic friction is the result of the sum of the angle of atomic friction and the slope angle between the contact surfaces. The latter is obtained from the determination of all possible contact slopes between the two surface profiles through an alternative signature function. Our theory is validated through numerical simulations of spheropolygons with fractal Koch surfaces and is applied to the description of frictional properties of Weierstrass-Mandelbrot surfaces. The agreement between simulations and theory suggests that for interpreting macroscopic frictional behavior, the descriptors of surface morphology should be defined from the signature function rather than from the slopes of the contacting surfaces.Civil Engineering Research Development Scheme provided by the School of Civil Engineering at The University of Sydney

Fractional-order projection of a chaotic system with hidden attractors and its passivity-based synchronization

This paper presents the fractional-order projection of a chaotic system, which delivers a collection of self-excited and hidden chaotic attractors as a function of a single system parameter. Based on an integer-order chaotic system and the proposed transformation, the fractional-order chaotic system obtains when the divergence of integer and fractional vector fields flows in the same direction. Phase portraits, bifurcation diagrams, and Lyapunov exponents validate the chaos generation. Apart from these results, two passivity-based fractional control laws are designed effectively for the integer and fractional-order chaotic systems. In both cases, the synchronization schemes depend on suitable storage functions given by the fractional Lyapunov theory. Several numerical experiments confirm the proposed approach and agree well with the mathematical deductions

Mercados municipales de Zapopan

Documento final del Proyecto de Aplicación Profesional en el que se presenta una investigación realizada en tres mercados del ayuntamiento de Zapopan: San Isidro, Francisco Sarabia y Tesistán. El objetivo de la investigación fue identificar las problemáticas, hacer propuestas y colaborar en la planeación de estrategias para mejorar las condiciones de los mercados y lograr un impacto positivo que se vea reflejado en las ventas. Para la investigación, se visitaron los mercados y se aplicaron encuestas a los locatarios, consumidores y administradores. La muestra que se usó para sacar el número de encuestas fue infinita con un nivel de confianza del 90 por ciento y un índice de error del 5 por ciento. En este proyecto trabajaron alumnos de las licenciaturas en Mercadotecnia, Administración de Empresas y Administración Financiera.ITESO, A.C

Air Pollution and Acute Respiratory Response in a Panel of Asthmatic Children along the U.S.–Mexico Border

Background: Concerns regarding the health impact of urban air pollution on asthmatic children are pronounced along the U.S.–Mexico border because of rapid population growth near busy border highways and roads. Objectives: We conducted the first binational study of the impacts of air pollution on asthmatic children in Ciudad Juarez, Mexico, and El Paso, Texas, USA, and compared different exposure metrics to assess acute respiratory response. Methods: We recruited 58 asthmatic children from two schools in Ciudad Juarez and two schools in El Paso. A marker of airway inflammation [exhaled nitric oxide (eNO)], respiratory symptom surveys, and pollutant measurements (indoor and outdoor 48-hr size-fractionated particulate matter, 48-hr black carbon, and 96-hr nitrogen dioxide) were collected at each school for 16 weeks. We examined associations between the pollutants and respiratory response using generalized linear mixed models. Results: We observed small but consistent associations between eNO and numerous pollutant metrics, with estimated increases in eNO ranging from 1% to 3% per interquartile range increase in pollutant concentrations. Effect estimates from models using school-based concentrations were generally stronger than corresponding estimates based on concentrations from ambient air monitors. Both traffic-related and non–traffic-related particles were typically more robust predictors of eNO than was nitrogen dioxide, for which associations were highly sensitive to model specification. Associations differed significantly across the four school-based cohorts, consistent with heterogeneity in pollutant concentrations and cohort characteristics. Models examining respiratory symptoms were consistent with the null. Conclusions: The results indicate adverse effects of air pollution on the subclinical respiratory health of asthmatic children in this region and provide preliminary support for the use of air pollution monitors close to schools to track exposure and potential health risk in this population