The contribution of YfdX and Ail/OmpX-like proteins to Salmonella Typhimurium stress resistance and virulence

Salmonella is a Gram-negative, food-borne pathogen and a major cause of worldwide morbidity and mortality. Salmonella encounters a wide variety of stressors in its environments, including changes in pH and heat, antimicrobial compounds, and reactive oxygen and nitrogen species. These conditions can result in serious damage to the bacterium, in particular the cell wall. To combat this, envelope stress response (ESR) pathways are in place to sense and respond to protein damage induced by such conditions and restore envelope homeostasis. There is a degree of overlap in terms of environmental cues and regulon members across the ESR pathway, many of which are important for Salmonella infection. We have been investigating genes that are co-regulated by more than one ESR, as we hypothesise that they will be more important for maintaining envelope homeostasis and might be potential therapeutic targets. We discovered that the hypothetical protein STM3030 and the outer membrane protein STM3031, which is an Ail/OmpX-like protein, were both transcriptionally regulated by the CpxR and BaeR ESR regulators in Salmonella. Both proteins have been associated with antibiotic resistance, with STM3030 having chaperone activity, and a Typhi homologue of STM3031 a role in adhesion to host cells. This study aims to characterise the roles of STM3030 and STM3031 in the S. Typhimurium ESR and infection. Using single and double deletion mutants, we have identified a role for these proteins in adhesion of Salmonella Typhimurium to Caco-2 epithelial cells, as well as determined their role in a range of envelope damaging conditions. The results of this study show that STM3030 and STM3031 cooperate during host cell adhesion, after which only STM3031 is needed for invasion of host cells, contradicting past studies, and revealing novel virulence functions of STM3030 and STM3031. This study highlights the need for further investigation into Salmonella molecular mechanisms of disease

Medicina homeopática : ¿existe evidencia científica?

Introducción: Actualmente el consumo de homeopatía se ha incrementado en los últimos años, y cada vez hay más personas que la utilizan. A pesar de que la homeopatía puede considerarse una terapia segura, las autoridades sanitarias indican que el principal peligro está cuando los pacientes utilizan estas pseudociencias como alternativa a las terapias convencionales, poniendo en peligro su propia salud e incluso su vida. El objetivo de este trabajo es conocer si existe evidencia científica o no para esta terapia. Material y métodos: Se realizó una revisión bibliográfica de artículos publicados en distintas bases de datos. De ellas se han seleccionado 26 artículos, 16 para el apartado evidencia científica. Como método complementario al trabajo, se elaboró un estudio piloto para ver la percepción que los alumnos de cuarto de enfermería como futuros profesionales tenían sobre esta pseudociencia. Resultados y discusión: Países como Francia, Alemania, Italia y España son los principales agentes del consumo de homeopatía. La mayoría de los autores resaltan que no hay evidencia científica sobre el uso de esta práctica mientras que por el otro lado concluyen que si. A pesar de que en algunos artículos indiquen cierta eficacia de su uso, los efectos no pueden ser superiores a los del placebo. Conclusiones: Las enfermeras pueden jugar un papel importante sobre la concienciación ciudadana y una formación adecuada del personal de enfermería es muy importante para un buen uso de los medicamentos homeopáticos.Grado en Enfermerí

Akt phosphorylation of HCV NS5B regulates polymerase activity and HCV infection

Hepatitis C virus (HCV) is a single-stranded RNA virus of positive polarity [ssRNA(+)] that replicates its genome through the activity of one of its proteins, called NS5B. This viral protein is responsible for copying the positive-polarity RNA genome into a negative-polarity RNA strand, which will be the template for new positive-polarity RNA genomes. The NS5B protein is phosphorylated by cellular kinases, including Akt. In this work, we have identified several amino acids of NS5B that are phosphorylated by Akt, with positions S27, T53, T267, and S282 giving the most robust results. Site-directed mutagenesis of these residues to mimic (Glu mutants) or prevent (Ala mutants) their phosphorylation resulted in a reduced NS5B in vitro RNA polymerase activity, except for the T267E mutant, the only non-conserved position of all those that are phosphorylated. In addition, in vitro transcribed RNAs derived from HCV complete infectious clones carrying mutations T53E/A and S282E/A were transfected in Huh-7.5 permissive cells, and supernatant viral titers were measured at 6 and 15 days post-transfection. No virus was rescued from the mutants except for T53A at 15 days post-transfection whose viral titer was statistically lower as compared to the wild type. Therefore, phosphorylation of NS5B by cellular kinases is a mechanism of viral polymerase inactivation. Whether this inactivation is a consequence of interaction with cellular kinases or a way to generate inactive NS5B that may have other functions are questions that need further experimental workMinisterio de Ciencia, Innovación y Universidades (MCIU), PI18/00210 from Instituto de Salud Carlos III, and S2018/BAA-4370 (PLATESA2 from Comunidad de Madrid/FEDER). CP was supported by the Miguel Servet program of the Instituto de Salud Carlos III (CPII19/00001), cofinanced by the European Regional Development Fund (ERDF). CG-C was supported by the predoctoral contract PRE2018-083422 from MCIU. CIBERehd (Centro de Investigación en Red de Enfermedades Hepáticas y Digestivas) was funded by the Instituto de Salud Carlos III. Institutional grants from the Fundación Ramón Areces and Banco Santander to the CBMS

Thin film nanostructuring at oblique angles by substrate patterning

It is demonstrated that, besides classical nanocolumnar arrays, the oblique angle geometry induces the growth of singular structures in the nanoscale when using wisely designed patterned substrates. Well-ordered array of crosses, cylindrical nanorods or hole structures arranged in square or hexagonal regular geometries are reported as examples, among others. The fundamental framework connecting substrate topography and film growth at oblique angles is presented, allowing the use of substrate patterning as a feasible thin film nanostructuring technique. A systematic analysis of the growth of TiO2 thin films on 4 different lithographic patterned substrates in 4 different scale lengths is also presented. A first conclusion is the existence of a height-based selective growth in the initial stages of the deposition, by which the film preferentially develops on top of the tallest substrate features. This behavior is maintained until the film reaches a critical thickness, the so-called Oblivion Thickness, above which the film topography becomes gradually independent of the substrate features. A general formula relating the spatial features of the pattern, the coarsening exponent and the Oblivion Thickness has been deduced.MCIN/AEI/and FEDER project PID2019-110430GB-C21MCIN/AEI/ and FEDER project PID2020-112620GB-I00MCIN/AEI/ and FEDER project PID2020-114270RA-I00MCIN/AEI/ and FEDER project RTI2018-098117-B-C21Junta de Andalucía PAIDI-2020 project P18-RT-3480Junta de Andalucía PAIDI-2020 project P18-RT-6079University of Seville VI PPIT-U

Thin film nanostructuring at oblique angles by substrate patterning

It is demonstrated that, besides classical nanocolumnar arrays, the oblique angle geometry induces the growth of singular structures in the nanoscale when using wisely designed patterned substrates. Well-ordered array of crosses, cylindrical nanorods or hole structures arranged in square or hexagonal regular geometries are reported as examples, among others. The fundamental framework connecting substrate topography and film growth at oblique angles is presented, allowing the use of substrate patterning as a feasible thin film nanostructuring technique. A systematic analysis of the growth of TiO2 thin films on 4 different lithographic patterned substrates in 4 different scale lengths is also presented. A first conclusion is the existence of a height-based selective growth in the initial stages of the deposition, by which the film preferentially develops on top of the tallest substrate features. This behavior is maintained until the film reaches a critical thickness, the so-called Oblivion Thickness, above which the film topography becomes gradually independent of the substrate features. A general formula relating the spatial features of the pattern, the coarsening exponent and the Oblivion Thickness has been deduced.The authors thank the financial support from MCIN/AEI/10.13039/ 501100011033 projects PID2019-110430GB-C21, PID2020-112620GBI00, PID2020-114270RA-I00 and RTI2018-098117-B-C21 (also financed by FEDER Una manera de hacer europa), the Junta de Andalucía (PAIDI- 2020 through projects P18-RT-3480 and P18-RT-6079, and through its 2019 PhD Researcher Hiring Program), the CSIC (2019AEP161 and 201860E050), the Regional Government of Madrid (project IND2017/ IND-7668 and YEI contract PEJ-2019-AI/IND-14451 with support from FSE), the H2020-EU.1.2.1-FET OPEN program (grant 899352, project SOUNDofICE, and the EFRE Infra-Pro project ChAMP), and the University of Seville (VI PPIT-US). The work is supported by the Deutsche Forschungsgemeinschaft (DFG, grant Scha 632/24, “Tailored Disorder” and Scha 632/27, “DFGGer ¨atezentrum”). This work is also supported by the free state of Thuringia under grants 2015 FGI 0025 305 (FastμXRD) and B715-10009 (BioMacroNano2020), all co-financed by the European Union within the framework of the European Regional Development Fund (ERDF). The service from the MiNa Laboratory at IMN-CNM (CSIC), funded from CM (project S2018/NMT-4291 TEC2SPACE), MINECO (project CSIC13-4E- 1794) and EU (FEDER, FSE), is also acknowledged.Peer reviewe

Nanoestructuración a la Carta de Películas Delgadas en Geometría de Ángulo Oblicuo Mediante el Control Topográfico del Sustrato

Trabajo presentado en el XVI Congreso Nacional de Materiales CNMAT 2022, celebrado en Ciudad Real (España), del 28 de junio al 1 de julio de 2022La técnica de pulverización catódica operada en geometría de ángulo oblicuo es bien conocida por permitir el crecimiento de películas delgadas nanocolumnares sobre sustratos planos. En otro tipo de sustratos, e.g. rugosos o litografiados, la casuística es variada, apareciendo estructuras complejas y diversas, incluso para espesores del orden de la micra. Estos resultados sugieren la existencia de una fuerte conexión entre el crecimiento de la película y la topografía del sustrato, que podría utilizarse para obtener un mayor control nanoestructural. En esta presentación se analiza teórica y experimentalmente la relación entre ambos aspectos al utilizar la técnica de pulverización catódica a ángulo oblicuo. Se demuestra la posibilidad de crecer estructuras singulares como, por ejemplo, cruces nanopilares o incluso de huecos dentro de una matriz compacta, ordenados de acuerdo a un patrón regular con distancias típicas del orden de cientos de nanómetros (ver Figura 1). Se describe, por lo tanto, el marco conceptual que permitiría que las técnicas actuales de litografía superficial se puedan utilizar como técnicas efectivas de control nanoestructural de películas delgadas. Como resultado, se demuestran varios principios que definen los diferentes estadios de la deposición que servirían como guías para el diseño inteligente del sustrato e inducir crecimientos a la carta. Estos principios se han validado experimentalmente al crecer diferentes películas delgadas sobre un total de 16 sustratos litografiados con diferentes topografías, patrones y escalas típicas por debajo de la micra, así como en otros sustratos con rugosidad intrínseca sometidos a diferentes tipos de pulido

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Frecuencia y consecuencias de la infidelidad en hombres y mujeres

Los casos de infidelidad han aumentado notablemente en los últimos tiempos, probablemente debido a los cambios sociales y de interacción entre hombres y mujeres. El desarrollo de la sociedad occidental favorece la interacción entre personas de ambos sexos. Así, un 30% de las mujeres y un 50% de los hombres en España han afirmado haber sido infieles en algún momento de su vida. Sin embargo, podría ocurrir que estos datos fuesen más impactantes todavía. El objetivo del presente estudio ha sido evaluar la frecuencia de infidelidad en hombres y mujeres, analizando también las consecuencias psicológicas de dicha infidelidad. La hipótesis propone que los hombres serán más infieles que las mujeres, y que la infidelidad repercutirá de forma diferencial en ambos sexos. Participaron voluntariamente 458 estudiantes universitarios (101 hombres y 357 mujeres). La media de edad era de 20,59 (DT = 1,78), y el rango entre 18 y 25 años. Se les administró una escala modificada de la Escala de celos e infidelidad de David Buss mediante una plataforma online: Google Forms. Los análisis mostraron que las mujeres son más infieles que los hombres. Además, después de sufrir una infidelidad, las mujeres experimentan más tristeza y deseo de venganza que los hombres, y éstos más sintomatología depresiva que las mujeres. Este trabajo rompe con la tendencia existente respecto a que los hombres son más infieles que las mujeres. Asimismo, la infidelidad en general repercute de forma diferencial en hombres y en mujeres, probablemente por efecto de los procesos de socialización.Cases of infidelity have increased notably in recent times, probably due to social changes and interaction between men and women. The development of Western society favors interaction between people of both sexes. Thus, 30% of women and 50% of men in Spain have claimed to have been unfaithful at some point in their life. However, it could happen that these data were even more shocking. The objective of this study has been to evaluate the frequency of infidelity in men and women, also analyzing the psychological consequences of said infidelity. The hypothesis proposes that men will be more unfaithful than women, and that infidelity will have a differential impact on both genders. 458 university students participated voluntarily (101 men and 357 women). The mean age was 20.59 (SD = 1.78), and the range was between 18 and 25 years. They were administered a modified scale of the David Buss Jealousy and Infidelity Scale through an online platform: Google Forms. The analyzes showed that women are more unfaithful than men. In addition, after suffering an infidelity, women experience more sadness and desire for revenge than men, and men experience more depressive symptoms than women. This work breaks with the existing trend that men are more unfaithful than women. Moreover, infidelity in general has a differential impact on men and women, probably due to the effect of socialization processes