Increased salt concentration promotes competitive block of OmpF channel by protons

Porins are channel-forming proteins that are located in the outer membranes (OM) of Gram-negative bacteria and allow the influx of hydrophilic nutrients and the extrusion of waste products. The fine regulation of the ion transport through these wide channels could play an important role in the survival of the bacteria in acidic media. We investigate here the mechanism responsible for the pH sensitivity of the trimeric porin OmpF, of Escherichia coli. Planar lipid bilayer electrophysiology and site-directed mutagenesis were used to study the effect of pH on the ion conductive properties of the OmpF channel in its fully open, “nongated” conformation. At low pH we observe a large drop in the OmpF open channel conductance that is accompanied by a substantial increase of the current noise. These channel features are strongly dependent on the salt concentration and we propose that they are originated by competitive binding of cations and protons occurring in the narrow central constriction of the channel. This subtlemechanismreveals to be capital for the channel function because it not only drives the channel sensitivity to pH but is also indispensable for the particularly efficient permeation mechanism of the channel at physiological conditions (~neutral pH)

Malignant Solitary Fibrous Tumour of the Breast Mimicking a Benign Tumor

Solitary fibrous tumour (SFT) of the breast is exceedingly uncommon. Radiological assessment usually shows benign features. We report on a case of malignant SFT of the breast, while emphasizing the need for additional immunostains to reach a definitive diagnosis. Standard treatment consists of lesion removal with adequate margins

Revisiting the usefulness of the short acute octreotide test to predict treatment outcomes in acromegaly

Acromegaly; Acute octreotide test; PredictionAcromegalia; Test agudo de octreotida; PredicciónAcromegàlia; Test agut d'octreòtid; PrediccióIntroduction: We previously described that a short version of the acute octreotide test (sAOT) can predict the response to first-generation somatostatin receptor ligands (SRLs) in patients with acromegaly. We have prospectively reassessed the sAOT in patients from the ACROFAST study using current ultra-sensitive GH assays. We also studied the correlation of sAOT with tumor expression of E-cadherin and somatostatin receptor 2 (SSTR2) . Methods: A total of 47 patients treated with SRLs for 6 months were evaluated with the sAOT at diagnosis and correlated with SRLs’ response. Those patients whose IGF1 decreased to <3SDS from normal value were considered responders and those whose IGF1 was ≥3SDS, were considered non-responders. The 2 hours GH value (GH2h) after s.c. administration of 100 mcg of octreotide was used to define predictive cutoffs. E-cadherin and SSTR2 immunostaining in somatotropinoma tissue were investigated in 24/47 and 18/47 patients, respectively. Results: In all, 30 patients were responders and 17 were non-responders. GH2h was 0.68 (0.25-1.98) ng/mL in responders vs 2.35 (1.59-9.37) ng/mL in non-responders (p<0.001). GH2h = 1.4ng/mL showed the highest ability to identify responders (accuracy of 81%, sensitivity of 73.3%, and specificity of 94.1%). GH2h = 4.3ng/mL was the best cutoff for non-response prediction (accuracy of 74%, sensitivity of 35.3%, and specificity of 96.7%). Patients with E-cadherin-positive tumors showed a lower GH2h than those with E-cadherin-negative tumors [0.9 (0.3-2.1) vs 3.3 (1.5-12.1) ng/mL; p<0.01], and patients with positive E-cadherin presented a higher score of SSTR2 (7.5 ± 4.2 vs 3.3 ± 2.1; p=0.01). Conclusion: The sAOT is a good predictor tool for assessing response to SRLs and correlates with tumor E-cadherin and SSTR2 expression. Thus, it can be useful in clinical practice for therapeutic decision-making in patients with acromegaly.The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the Instituto de Salud Carlos III (PMP15/00027, co-funded by the European Union-ERDF; and PMP22/00021, funded by the European Union -NextGenerationEU); and Novartis through the REMAH (Registro Español Molecular de Adenomas Hipofisarios) consortium of the SEEN (Sociedad Española de Endocrinología y Nutrición). Novartis was not involved in the study design, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication

Predicting workaholism in Spain: a discrete mathematical model

At the present time one of the most 'desirable' behavioural addictions that any person could develop is workaholism, a negative psychological state characterized by working excessively and compulsively. In our society, the successful person is one who spends all of their time working. Moreover, a common pattern of company management consists of stressing and putting pressure on employees to achieve the maximum profit. This trend has increased with the economic crisis in Spain and over the world. As a consequence, the terms hard working and workaholism are easily confounded, but their effects on the companies are highly different in terms of productivity. This paper proposes a discrete mathematical model to forecast the development of workaholism in Spain in the next years. A questionnaire is used in order to measure and classify our sample in subpopulations by their level of addiction. Then, different economic scenarios are simulated. Finally, economic and social consequences of this addiction are studied and public health recommendations are suggested.De La Poza, E.; Líbano, MD.; García, I.; Jódar Sánchez, LA.; Merello Giménez, P. (2014). Predicting workaholism in Spain: a discrete mathematical model. International Journal of Computer Mathematics. 91(2):233-240. https://doi.org/10.1080/00207160.2013.783205S233240912Schou Andreassen, C., Ursin, H., & Eriksen, H. R. (2007). The relationship between strong motivation to work, «workaholism», and health. Psychology & Health, 22(5), 615-629. doi:10.1080/14768320600941814Bowling, N. A., Beehr, T. A., & Swader, W. M. (2005). Giving and receiving social support at work: The roles of personality and reciprocity. Journal of Vocational Behavior, 67(3), 476-489. doi:10.1016/j.jvb.2004.08.004Burke, R. J., & Koksal, H. (2002). Workaholism among a Sample of Turkish Managers and Professionals: An Exploratory Study. Psychological Reports, 91(1), 60-68. doi:10.2466/pr0.2002.91.1.60Burke, R. J., Oberklaid, F., & Burgess, Z. (2004). Workaholism among Australian women psychologists: antecedents and consequences. Women in Management Review, 19(5), 252-259. doi:10.1108/09649420410545971De la Poza, E., Guadalajara, N., Jódar, L., & Merello, P. (2013). Modeling Spanish anxiolytic consumption: Economic, demographic and behavioral influences. Mathematical and Computer Modelling, 57(7-8), 1619-1624. doi:10.1016/j.mcm.2011.10.020Duato, R., & Jódar, L. (2013). Mathematical modeling of the spread of divorce in Spain. Mathematical and Computer Modelling, 57(7-8), 1732-1737. doi:10.1016/j.mcm.2011.11.020Fry, L. W., & Cohen, M. P. (2008). Spiritual Leadership as a Paradigm for Organizational Transformation and Recovery from Extended Work Hours Cultures. Journal of Business Ethics, 84(S2), 265-278. doi:10.1007/s10551-008-9695-2García, I., Jódar, L., Merello, P., & Santonja, F.-J. (2011). A discrete mathematical model for addictive buying: Predicting the affected population evolution. Mathematical and Computer Modelling, 54(7-8), 1634-1637. doi:10.1016/j.mcm.2010.12.012Gustafsson, P. E., Janlert, U., Virtanen, P., & Hammarström, A. (2012). The association between long-term accumulation of temporary employment, the cortisol awakening response and circadian cortisol levels. Psychoneuroendocrinology, 37(6), 789-800. doi:10.1016/j.psyneuen.2011.09.011Hochschild, A. (1997). The Time Bind. WorkingUSA, 1(2), 21-29. doi:10.1111/j.1743-4580.1997.tb00019.xNelder, J. A., & Mead, R. (1965). A Simplex Method for Function Minimization. The Computer Journal, 7(4), 308-313. doi:10.1093/comjnl/7.4.308Ng, T. W. H., Sorensen, K. L., & Feldman, D. C. (2006). Dimensions, antecedents, and consequences of workaholism: a conceptual integration and extension. Journal of Organizational Behavior, 28(1), 111-136. doi:10.1002/job.424W.E. Oates,Confessions of a Workaholic: The Facts about Work Addiction, World Publishing Company, New York, 1971.Raafat, R. M., Chater, N., & Frith, C. (2009). Herding in humans. Trends in Cognitive Sciences, 13(10), 420-428. doi:10.1016/j.tics.2009.08.002Robinson, B. E., & Post, P. (1997). Risk of Addiction to Work and Family Functioning. Psychological Reports, 81(1), 91-95. doi:10.2466/pr0.1997.81.1.91Schaufeli, W. B., & Bakker, A. B. (2004). Job demands, job resources, and their relationship with burnout and engagement: a multi-sample study. Journal of Organizational Behavior, 25(3), 293-315. doi:10.1002/job.248Schaufeli, W. B., Bakker, A. B., & Salanova, M. (2006). The Measurement of Work Engagement With a Short Questionnaire. Educational and Psychological Measurement, 66(4), 701-716. doi:10.1177/0013164405282471Schaufeli, W. B., Taris, T. W., & van Rhenen, W. (2008). Workaholism, Burnout, and Work Engagement: Three of a Kind or Three Different Kinds of Employee Well-being? Applied Psychology, 57(2), 173-203. doi:10.1111/j.1464-0597.2007.00285.xSchaufeli, W. B., Bakker, A. B., van der Heijden, F. M. M. A., & Prins, J. T. (2009). Workaholism, burnout and well-being among junior doctors: The mediating role of role conflict. Work & Stress, 23(2), 155-172. doi:10.1080/02678370902834021Shimazu, A., Schaufeli, W. B., & Taris, T. W. (2010). How Does Workaholism Affect Worker Health and Performance? The Mediating Role of Coping. International Journal of Behavioral Medicine, 17(2), 154-160. doi:10.1007/s12529-010-9077-xSonnentag, S. (2003). Recovery, work engagement, and proactive behavior: A new look at the interface between nonwork and work. Journal of Applied Psychology, 88(3), 518-528. doi:10.1037/0021-9010.88.3.518Yaniv, G. (2011). Workaholism and marital estrangement: A rational-choice perspective. Mathematical Social Sciences, 61(2), 104-108. doi:10.1016/j.mathsocsci.2010.11.00

A copper switch for inducing CRISPR/Cas9-based transcriptional activation tightly regulates gene expression in Nicotiana benthamiana

[EN] Background CRISPR-based programmable transcriptional activators (PTAs) are used in plants for rewiring gene networks. Better tuning of their activity in a time and dose-dependent manner should allow precise control of gene expression. Here, we report the optimization of a Copper Inducible system called CI-switch for conditional gene activation in Nicotiana benthamiana. In the presence of copper, the copper-responsive factor CUP2 undergoes a conformational change and binds a DNA motif named copper-binding site (CBS). Results In this study, we tested several activation domains fused to CUP2 and found that the non-viral Gal4 domain results in strong activation of a reporter gene equipped with a minimal promoter, offering advantages over previous designs. To connect copper regulation with downstream programmable elements, several copper-dependent configurations of the strong dCasEV2.1 PTA were assayed, aiming at maximizing activation range, while minimizing undesired background expression. The best configuration involved a dual copper regulation of the two protein components of the PTA, namely dCas9:EDLL and MS2:VPR, and a constitutive RNA pol III-driven expression of the third component, a guide RNA with anchoring sites for the MS2 RNA-binding domain. With these optimizations, the CI/dCasEV2.1 system resulted in copper-dependent activation rates of 2,600-fold and 245-fold for the endogenous N. benthamiana DFR and PAL2 genes, respectively, with negligible expression in the absence of the trigger. Conclusions The tight regulation of copper over CI/dCasEV2.1 makes this system ideal for the conditional production of plant-derived metabolites and recombinant proteins in the field.This work has been funded by EU Horizon 2020 Project Newcotiana Grant 760331, PID2019-108203RB-100 Plan Nacional I + D, Spanish Ministry of Economy and Competitiveness and 'ERACoBioTech' Project SUSPHIRE Grant No. 722361. Vazquez-Vilar, M. is recipient of APOSTD/2020/096 (Generalitat Valenciana and Fondo Social Europeo post-doctoral grant). Garcia-Perez, E. is recipient of ACIF-2020 fellowship (Generalitat Valenciana). Diego-Martin, B. and Moreno-Gimenez, E. are recipients of FPU fellowships. Selma, S. is recipient of FPI fellowship.García-Pérez, E.; Diego-Martín, B.; Quijano-Rubio, A.; Moreno-Giménez, E.; Selma, S.; Orzáez Calatayud, DV.; Vázquez-Vilar, M. (2022). A copper switch for inducing CRISPR/Cas9-based transcriptional activation tightly regulates gene expression in Nicotiana benthamiana. BMC Biotechnology. 22(1):1-13. https://doi.org/10.1186/s12896-022-00741-x11322

An F2 Barley Population as a Tool for Teaching Mendelian Genetics

In the context of a general genetics course, mathematical descriptions of Mendelian inheritance and population genetics are sometimes discouraging and students often have serious misconceptions. Innovative strategies in expositive classes can clearly encourage student’s motivation and participation, but laboratories and practical classes are generally the students’ favourite academic activities. The design of lab practices focused on learning abstract concepts such as genetic interaction, genetic linkage, genetic recombination, gene mapping, or molecular markers is a complex task that requires suitable segregant materials. The optimal population for pedagogical purposes is an F2 population, which is extremely useful not only in explaining different key concepts of genetics (as dominance, epistasis, and linkage) but also in introducing additional curricular tools, particularly concerning statistical analysis. Among various model organisms available, barley possesses several unique features for demonstrating genetic principles. Therefore, we generated a barley F2 population from the parental lines of the Oregon Wolfe Barley collection. The objective of this work is to present this F2 population as a model to teach Mendelian genetics in a medium–high-level genetics course. We provide an exhaustive phenotypic and genotypic description of this plant material that, together with a description of the specific methodologies and practical exercises, can be helpful for transferring our fruitful experience to anyone interested in implementing this educational resource in his/her teaching

Teaching difficulties. An analysis of the perceptions of Master's Degree Teacher Education students

Esta publicación es parte del proyecto «Diagnóstico de las competencias docentes del profesorado no universitario de la provincia de Valencia e identificación de las nuevas necesidades post-pandemia COVID-19. Propuestas de formación docente», de I+D+i CIGE/2021/014, financiado por la Conselleria de Innovación, Universidades, Ciencia y Sociedad Digital (GE/2022).El profesorado es un elemento clave en la educación y su formación y concepción de la enseñanza determinan el éxito escolar. Este artículo trata de analizar las dificultades que autoperciben los estudiantes del Máster del Profesorado en su futuro desempeño profesional y establecer propuestas de mejora para su formación. Se analiza el patrón de puntuaciones de los estudiantes y las diferencias en función de la universidad de procedencia y del sexo. Se estudia la relación de predicción entre las Dificultades académicas y sociales en las Dificultades organizacionales, con las Dificultades materiales como mediadoras y la edad como factor influyente en esta relación. Es un estudio descriptivo y predictivo de las Dificultades organizacionales y materiales, donde se presta especial atención a las variables universidad de procedencia, edad y sexo. Participan 409 estudiantes, de distintas universidades valencianas. Se utiliza el Inventario de Problemas de Enseñanza. Entre los resultados destacan las dificultades para: relacionarse con las familias de los alumnos, organizar el tiempo de clase y gestionar el aula y la disciplina. Estos resultados coinciden con los de otras investigaciones. Además, las alumnas más mayores perciben mayores dificultades materiales; y aquellas que declaran mayores dificultades académicas también presentan mayores dificultades organizacionales. Se plantea la necesidad de implantar ciertas metodologías, potenciar la relación Universidad-escuela y mejorar el periodo de prácticas. Por lo que respecta al modelo causal analizado, se concluye que las Dificultades académicas y sociales influyen de forma directa sobre las organizacionales y que las materiales tienen un efecto mediador en esta relación.Teachers are one of the key elements in education and their training and conception of teaching influence school success. This article tries to analyze the difficulties self-perceived by the students of the master’s degree in teaching in their future professional performance and to establish proposals for improvement in their training. The pattern of students' scores and the differences according to the university of origin and gender are analyzed. The predictive relationship between academic and social difficulties in organizational difficulties is studied, with material difficulties as mediators and age as an influential factor in this relationship. It is a descriptive and predictive study of organizational and material difficulties, where special attention is paid to the variable’s university of origin, age, and gender. A total of 409 students from different Valencian universities participated. The Teaching Problems Inventory was used. Among the results, the following difficulties stand out: difficulties in relating with the students' families, organizing class time, and managing the classroom and discipline. These results coincide with those of other research. In addition, older students perceive greater material difficulties; and those who report greater academic difficulties also present greater organizational difficulties. There is a need to implement certain methodologies, to strengthen the university-school relationship and to improve the internship period. About the causal model analyzed, it is concluded that academic and social difficulties have a direct influence on organizational difficulties and that material difficulties have a mediating effect on this relationship.Conselleria de Innovación, Universidades, Ciencia y Sociedad Digital (GE/2022) CIGE/2021/01

Environmental LCA and carbon footprint of cauliflower as produced in Southeast Spain

Southern Spain has an optimal climate for growing fruits and vegetables. Over 39,534 ha are currently dedicated to the production of cauliflower and broccoli in Spain, 33% of which correspond to the Region of Murcia. This type of intensive agriculture causes environmental impacts which must be quantified and minimized as much as possible. This study details the Life Cycle Assessment (LCA) of cauliflower production with a cradle-to-farm-gate approach using precise and updated primary data from local producers. Foreground inventory data was collected for the nursery and on-field stages, including energy use, consumption, application and diffusion of fertilizers and pesticides, machinery and transport to the packaging center. Ecoinvent v3.6 datasets were adapted to the characteristics of the system for background inventory and the EF 3.0 method was used for evaluation. The carbon footprint of 1 kg of cauliflower was estimated at 91.2 g CO2eq. Impact values for the same functional unit in other categories were as follows: Photochemical ozone formation 3.33E-04 kg NMVOC eq., Acidification 3.41E-04 mol H+ eq., Freshwater eutrophication 2.27E-05 kg P eq. The mitigation practices in cauliflower production should focus on energy use during irrigation and reduced use of pesticides.This research was funded by the Fondo Europeo de Desarrollo Regional/Ministerio de Ciencia e Innovación-Agencia Estatal de Investigación (FEDER/MICINN-AEI), project RTI2018-099139-B-C21 (Karp0-LIFE). Laura Rasines acknowledges financial support from the Spanish Ministerio de Ciencia e Innovación through the “Ayudas para contratos predoctorales para la formación de doctores 2019” Program [PRE2019-090573]

Sustainability and energy analysis of the lettuce post-harvest stage by Integration of PV

Nowadays, the food sector is improving its energy consumption to achieve a more sustainable industry, and also in economic and environmental terms. Aiming to mitigate global warming and fossil fuel dependence, it is necessary to determine the carbon footprint to assess the main impacts of a typical food production system. Among the different solutions, Life Cycle Assessment is a suitable method to evaluate the environmental impact throughout the entire supply chain. Under that framework, this paper aims to compare the environmental impact of energy consumption in lettuce post-harvest activities using two energy scenarios: current Spanish mix power generation, and sustainable Spanish mix generation by optimizing self-consumption PV power plants and using gate-togate LCA. The global warming potential for years and Cumulative Energy Demand are also determined. As a result, we obtained 25.8 gCO2eq and 479.3 kJ/kg; and 17.8 gCO2eq and 398.5 kJ/kg, respectively, for both Spanish generation mix scenarios. Refrigeration energy consumption is the most demanding stage, entailing major emission contributions. PV installations can minimize said impact by 32 % in both impact categories. Further investigation should address the analysis of implementing renewable energy sources in other fresh vegetable supply chain stages, creating a more sustainable food industry.This research was funded by Fondo Europeo de Desarrollo Regional/Ministerio de Ciencia e Innovación-Agencia Estatal de Investigación (FEDER/MICINN-AEI), project RTI2018-099139-B-C21 (Karp0-LIFE). Laura Rasines acknowledges financial support from the Spanish Ministerio de Ciencia e Innovación through “Ayudas para contratos predoctorales para la formación de doctores 2019” Program [PRE2019-090573]