Histological Study of Glandular Variability in the Skin of the Natterjack Toad-Epidalea calamita (Laurenti, 1768)-Used in Spanish Historical Ethnoveterinary Medicine and Ethnomedicine

Simple Summary Common toads, including the natterjack toad (Epidalea calamita), have been used since ancient times for remedies, and thus constitute excellent biological material for pharmacological and natural product research. After a previous analysis of the historical-folk therapeutic use of amphibians in Spain, a histological study was carried out to provide a complementary ethnopharmacological view through the analysis of the integumentary heterogeneity of the serous (venom) and mucous glands from two adult specimens. Plastic-embedded semi-thin sections showed that serous/venom glands are cytologically homogeneous in spite of their genetic and biochemical complexity, leading to a cocktail that remains stored until extrusion. On the contrary, mucous glands, working continuously, show a more complex cytological variation and regional heterogeneity, which suggests an adaptive variability, leading to an invisible topographic map of skin toxicity. Natterjack toad-based folk remedies are usually extracted from the whole animal as a therapeutic unit in ethnoveterinary practice. However, a new ethnopharmacological vision could emerge from the study of tegumentary regional variation. Common toads have been used since ancient times for remedies and thus constitute excellent biological material for pharmacological and natural product research. According to the results of a previous analysis of the therapeutic use of amphibians in Spain, we decided to carry out a histological study that provides a complementary view of their ethnopharmacology, through the natterjack toad (Epidalea calamita). This species possesses a characteristic integument, where the parotoid glands stand out, and it has been used in different ethnoveterinary and ethnomedical practices. This histological study of their glandular variability allow us to understand the stages through which the animal synthesises and stores a heterogeneous glandular content according to the areas of the body and the functional moment of the glands. To study tegumentary cytology, a high-resolution, plastic embedding, semi-thin (1 micron) section method was applied. Up to 20 skin patches sampled from the dorsal and ventral sides were processed from the two adult specimens collected, which were roadkill. Serous/venom glands display a genetic and biochemical complexity, leading to a cocktail that remains stored (and perhaps changes over time) until extrusion, but mucous glands, working continuously to produce a surface protection layer, also produce a set of active protein (and other) substances that dissolve into mucous material, making a biologically active covering. This study provides a better understanding of the use of traditional remedies in ethnoveterinary medicine

Trastorno por Déficit de Atención con Hiperactividad: Ritmo Circanual en el Mes de Nacimiento

Estudiamos la existencia de ritmo circanual en el mes de nacimiento en participantes con trastorno de déficit de atención e hiperactividad (TDAH) y analizamos la asociación entre meses de nacimiento y TDAH. La muestra incluye 10978 participantes (1778 TDAH / 9200 no TDAH), entre 3 y 18 años, reclutados mediante muestreo consecutivo de primeras consultas atendidas en salud mental entre 1992 y 2021. Los participantes con TDAH presentan un ritmo circanual significativo en los meses de nacimiento, con una acrofase en octubre. Nacer en el último cuatrimestre del año incrementa significativamente la probabilidad de ser diagnosticado TDAH, controlando el efecto de sexo y edad. Con el transcurso de los meses del año, existe una tendencia lineal creciente significativa de ser diagnosticado de TDAH, no observada en población general, ni en casos sin TDAH. Es necesario tener precaución en el diagnóstico y tratamiento de los niños nacidos en los últimos meses del año, que, por su mayor inmadurez en comparación con los demás niños de la clase, pudieran ser diagnosticados y tratados erróneamente como TDAHAttention Deficit Hyperactivity Disorder: Circannual Rhythm in the Month of Birth. We studied the existence of circanual rhythm in the month of birth in participants with attention deficit hyperactivity disorder (ADHD) and analyzed the association between months of birth and ADHD. We analyzed 10,978 participants (1,778 ADHD/9,200 non-ADHD), aged 3 to 18 years. A consecutive sample of first visits to mental health between 1992 and 2021 is used. Participants with ADHD exhibit a significant circannual rhythm in the months of birth, with an acrophase in October. Being born in the last quarter of the year significantly increases the probability of being diagnosed with ADHD, controlling for the effect of sex and age. As the months of the year go by, there is a significant increasing linear trend of being diagnosed with ADHD, which is not observed neither in general population nor in cases without ADHD. Caution is necessary in diagnosis and treatment of children born in the last months of year, who, due to their greater immaturity compared to the other children in class, could be misdiagnosed and treated as ADH

Parámetros genéticos para producción de leche de ganado Holstein en dos modalidades de control de producción

Variance components and genetic parameters were estimated for total milk production at first lactation (MP1), milkyield adjusted to 305 d and adult equivalent at the first lactation (MP1std), total milk production of the first fivelactations (MP5) and milk yield adjusted to 305 d and mature equivalent of the first five lactations (MP5std). Thedatabases of the Mexican Holstein Association (MHA, n= 43,668) and of the National Bank of Dairy Information(NBDI, n= 120,217) were used. Variances were estimated by REML, using a simple animal model for MP1 and MP1stdand a repeatability animal model for MP5 and MP5std. Heritability estimates ranged from low to moderate for thefirst lactation (0.17 ± 0.009 to 0.49 ± 0.019) and for the first five lactations (0.16 ± 0.006 to 0.41 ± 0.004). Therepeatabilities for MP5 and MP5std ranged from 0.32 ± 0.002 to 0.41 ± 0.004. The inclusion of information of theNBDI on the national evaluations made possible the incorporation of production data that had not been taken intoconsideration before. This inclusion not only improved the accuracy of sire breeding values   for milk production, butalso allowed the prediction of breeding values of more foreign and domestic animals with progeny in Mexico.Se estimaron componentes de varianza y parámetros genéticos para producción de leche total a la primera lactancia (PL1), producción de leche ajustada a 305 días y a equivalente adulto de la primera lactancia (PL1std), producción de leche total de las cinco primeras lactancias (PL5) y producción de leche ajustada a 305 días y a equivalente adulto de las primeras 5 lactancias (PL5std). Se utilizaron las bases de datos de la Asociación Holstein de México (AHM; n= 43,668) y del Banco Nacional de Información Lechera (BNIL; n= 120,217). Las varianzas fueron estimadas mediante REML, utilizando un modelo animal simple para PL1 y PL1std y un modelo animal de repetibilidad para PL5 y PL5std. Las heredabilidades estimadas fueron desde bajas a moderadas para la primera lactancia (0.17 ± 0.009 a 0.49 ± 0.019) y para las primeras cinco lactancias (0.16 ± 0.006 a 0.41 ± 0.004). Las repetibilidades para PL5 y PL5std tuvieron un rango de 0.32 ± 0.002 a 0.41 ± 0.004. La inclusión de la información del BNIL en las evaluaciones genéticas permitió incorporar datos de producción que no se estaban tomando en cuenta. Esto no solamente mejoró la precisión de los valores genéticos de los sementales para producción de leche, sino que también permitió la predicción de los valores genéticos de animales nacionales y extranjeros con progenies en México

Parámetros genéticos para producción de leche de ganado Holstein en dos modalidades de control de producción

Variance components and genetic parameters were estimated for total milk production at first lactation (MP1), milkyield adjusted to 305 d and adult equivalent at the first lactation (MP1std), total milk production of the first fivelactations (MP5) and milk yield adjusted to 305 d and mature equivalent of the first five lactations (MP5std). Thedatabases of the Mexican Holstein Association (MHA, n= 43,668) and of the National Bank of Dairy Information(NBDI, n= 120,217) were used. Variances were estimated by REML, using a simple animal model for MP1 and MP1stdand a repeatability animal model for MP5 and MP5std. Heritability estimates ranged from low to moderate for thefirst lactation (0.17 ± 0.009 to 0.49 ± 0.019) and for the first five lactations (0.16 ± 0.006 to 0.41 ± 0.004). Therepeatabilities for MP5 and MP5std ranged from 0.32 ± 0.002 to 0.41 ± 0.004. The inclusion of information of theNBDI on the national evaluations made possible the incorporation of production data that had not been taken intoconsideration before. This inclusion not only improved the accuracy of sire breeding values   for milk production, butalso allowed the prediction of breeding values of more foreign and domestic animals with progeny in Mexico.Se estimaron componentes de varianza y parámetros genéticos para producción de leche total a la primera lactancia (PL1), producción de leche ajustada a 305 días y a equivalente adulto de la primera lactancia (PL1std), producción de leche total de las cinco primeras lactancias (PL5) y producción de leche ajustada a 305 días y a equivalente adulto de las primeras 5 lactancias (PL5std). Se utilizaron las bases de datos de la Asociación Holstein de México (AHM; n= 43,668) y del Banco Nacional de Información Lechera (BNIL; n= 120,217). Las varianzas fueron estimadas mediante REML, utilizando un modelo animal simple para PL1 y PL1std y un modelo animal de repetibilidad para PL5 y PL5std. Las heredabilidades estimadas fueron desde bajas a moderadas para la primera lactancia (0.17 ± 0.009 a 0.49 ± 0.019) y para las primeras cinco lactancias (0.16 ± 0.006 a 0.41 ± 0.004). Las repetibilidades para PL5 y PL5std tuvieron un rango de 0.32 ± 0.002 a 0.41 ± 0.004. La inclusión de la información del BNIL en las evaluaciones genéticas permitió incorporar datos de producción que no se estaban tomando en cuenta. Esto no solamente mejoró la precisión de los valores genéticos de los sementales para producción de leche, sino que también permitió la predicción de los valores genéticos de animales nacionales y extranjeros con progenies en México

On-Surface Thermal Stability of a Graphenic Structure Incorporating a Tropone Moiety

On-surface synthesis, complementary to wet chemistry, has been demonstrated to be a valid approach for the synthesis of tailored graphenic nanostructures with atomic precision. Among the different existing strategies used to tune the optoelectronic and magnetic properties of these nanostructures, the introduction of non-hexagonal rings inducing out-of-plane distortions is a promising pathway that has been scarcely explored on surfaces. Here, we demonstrate that non-hexagonal rings, in the form of tropone (cycloheptatrienone) moieties, are thermally transformed into phenyl or cyclopentadienone moieties upon an unprecedented surface-mediated retro–Buchner-type reaction involving a decarbonylation or an intramolecular rearrangement of the CO unit, respectivel

S-Nitrosation of E3 Ubiquitin Ligase Complex Components Regulates Hormonal Signalings in Arabidopsis

E3 ubiquitin ligases mediate the last step of the ubiquitination pathway in the ubiquitin-proteasome system (UPS). By targeting transcriptional regulators for their turnover, E3s play a crucial role in every aspect of plant biology. In plants, SKP1/CULLIN1/F-BOX PROTEIN (SCF)-type E3 ubiquitin ligases are essential for the perception and signaling of several key hormones including auxins and jasmonates (JAs). F-box proteins, TRANSPORT INHIBITOR RESPONSE 1 (TIR1) and CORONATINE INSENSITIVE 1 (COI1), bind directly transcriptional repressors AUXIN/INDOLE-3-ACETIC ACID (AUX/IAA) and JASMONATE ZIM-DOMAIN (JAZ) in auxin- and JAs-depending manner, respectively, which permits the perception of the hormones and transcriptional activation of signaling pathways. Redox modification of proteins mainly by S-nitrosation of cysteines (Cys) residues via nitric oxide (NO) has emerged as a valued regulatory mechanism in physiological processes requiring its rapid and versatile integration. Previously, we demonstrated that TIR1 and Arabidopsis thaliana SKP1 (ASK1) are targets of S-nitrosation, and these NO-dependent posttranslational modifications enhance protein-protein interactions and positively regulate SCFTIR1 complex assembly and expression of auxin response genes. In this work, we confirmed S-nitrosation of Cys140 in TIR1, which was associated in planta to auxin-dependent developmental and stress-associated responses. In addition, we provide evidence on the modulation of the SCFCOI1 complex by different S-nitrosation events. We demonstrated that S-nitrosation of ASK1 Cys118 enhanced ASK1-COI1 protein-protein interaction. Overexpression of non-nitrosable ask1 mutant protein impaired the activation of JA-responsive genes mediated by SCFCOI1 illustrating the functional relevance of this redox-mediated regulation in planta. In silico analysis positions COI1 as a promising S-nitrosation target, and demonstrated that plants treated with methyl JA (MeJA) or S-nitrosocysteine (NO-Cys, S-nitrosation agent) develop shared responses at a genome-wide level. The regulation of SCF components involved in hormonal perception by S-nitrosation may represent a key strategy to determine the precise time and site-dependent activation of each hormonal signaling pathway and highlights NO as a pivotal molecular player in these scenarios.Fil: Terrile, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Tebez, Nuria Malena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Colman, Silvana Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Mateos, Julieta Lisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Morato López, Esperanza. CENTRO DE BIOLOGIA MOLECULAR SEVERO OCHOA (CBMSO) ; UNIVERSIDAD AUTONOMA DE MADRID;Fil: Sánchez López, Nuria. CENTRO DE BIOLOGIA MOLECULAR SEVERO OCHOA (CBMSO) ; UNIVERSIDAD AUTONOMA DE MADRID;Fil: Izquierdo Álvarez, Alicia. No especifíca;Fil: Marina, Anabel. CENTRO DE BIOLOGIA MOLECULAR SEVERO OCHOA (CBMSO) ; UNIVERSIDAD AUTONOMA DE MADRID;Fil: Calderón Villalobos, Luz Irina A.. Donald Danforth Plant Science Center; Estados UnidosFil: Estelle, Mark. No especifíca;Fil: Martínez Ruiz, Antonio. No especifíca;Fil: Fiol, Diego Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Casalongue, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Iglesias, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentin

Regulation of SCF TIR1/AFB E3 ligase assembly by S-nitrosylation of Arabidopsis SKP1-like1 impacts on auxin signaling

The F-box proteins (FBPs) TIR1/AFBs are the substrate recognition subunits of SKP1–cullin–F-box (SCF) ubiquitin ligase complexes and together with Aux/IAAs form the auxin co-receptor. Although tremendous knowledge on auxin perception and signaling has been gained in the last years, SCFTIR1/AFBs complex assembly and stabilization are emerging as new layers of regulation. Here, we investigated how nitric oxide (NO), through S-nitrosylation of ASK1 is involved in SCFTIR1/AFBs assembly. We demonstrate that ASK1 is S-nitrosylated and S-glutathionylated in cysteine (Cys) 37 and Cys118 residues in vitro. Both, in vitro and in vivo protein-protein interaction assays show that NO enhances ASK1 binding to CUL1 and TIR1/AFB2, required for SCFTIR1/AFB2 assembly. In addition, we demonstrate that Cys37 and Cys118 are essential residues for proper activation of auxin signaling pathway in planta. Phylogenetic analysis revealed that Cys37 residue is only conserved in SKP proteins in Angiosperms, suggesting that S-nitrosylation on Cys37 could represent an evolutionary adaption for SKP1 function in flowering plants. Collectively, these findings indicate that multiple events of redox modifications might be part of a fine-tuning regulation of SCFTIR1/AFBs for proper auxin signal transduction.This work has been supported by grants from CONICET (PIP 0202 to M.C.T), Universidad Nacional de Mar del Plata and Agencia Nacional de Promoción Científica y Tecnológica, -Argentina (PICT 1167 to M.C.T and PICT 2421 to C.A.C); from the Spanish Government (PS09/00101 and PI12/00875 to A.M.R., cofinanced by the European Union ERDF), and by the Argentinian-Spanish Integrated Action ES/11/02 / PRIAIBAR- 2011-0782. A.M.R. is supported by the I3SNS programme (ISCIII, Spanish Government). The Proteomics Service of the CBMSO is a member of Proteored (PRB2-ISCIII), and is supported by grants PT13/ 0001/0024 and PT17/0019/0018 of Spanish Government (cofinanced by the European Union ERDF). Work in the laboratory of M.E is supported by grants from the National Institutes of Health (NIH) GM43644, The Howard Hughes Medical Institute and the Gordon and Betty Moore Foundation, US

Vaccination adjuvated against hepatitis B in Spanish National Healthcare System (SNS) workers typed as non-responders to conventional vaccines

[EN] Trial Design: An interventional, phase 4, single group assignment, without masking (open label), preventive clinical trial was carried out in health workers with biological risk in their tasks, who have been filed as non-responders to conventional vaccination against Hepatitis B. Methods: 67 health workers with biological risk in their tasks, who have been filed as non-responders to conventional vaccination against Hepatitis B, were enrolled in the Clinical Trial. All participants were from 18 years up to 64 years old. Inclusion Criteria: NHS workers -including university students doing their internships in health centres dependent on the National Health System (inclusion of students is regulated and limited by specific instructions on labour prevention in each autonomous community)- classified as non-responders. The criteria defining them as non-responders to the conventional hepatitis B vaccine is anti HBsAb titers < 10 mUI/ml following the application of six doses of conventional vaccine at 20 lg doses (two complete guidelines). The objective of this study was to provide Health workersstaff with an additional protection tool against hepatitis B infection, and to evaluate the efficacy of the adjuvanted vaccine in healthy non-responders to conventional hepatitis B vaccine. The primary outcome was the measurement of antibody antiHBs before the first Fendrix dose and a month after the administration of each dose. Other outcome was collection of adverse effects during administration and all those that could be related to the vaccine and that occur within 30 days after each dose. In this study, only one group was assigned. There was no randomization or masking. Results: The participants were recruited between April 13, 2018 and October 31, 2019. 67 participants were enrolled in the Clinical Trial and included the analyses. The primary immunisation consists of 4 separate 0.5 ml doses of Fendrix , administered at the following schedule: 1 month, 2 months and 6 months from the date of the first dose. Once the positivity was reached in any of the doses, the participant finished the study and was not given the following doses. 68.66% (46 out 67) had a positive response to first dose of Fendrix. 57.14% (12 out 21) had a positive response to second dose of Fendrix . 22.22% (2 out 9) had a positive response to third dose of Fendrix and 42.96% (3 out 7) had a positive response to last dose of Fendrix. Overall, 94.02% (64 out 67) of participants had a positive response to Fendrix . No serious adverse event occurred. Conclusions: The use of Fendrix , is a viable vaccine alternative for NHS workers classified as ‘‘nonresponders”. Revaccination of healthy non-responders with Fendrix, resulted in very high proportions of responders without adverse events. Trial registration: The trial was registered in the Spanish National Trial Register (REEC), ClinicalTrials.gov and inclusion has been stopped (identifier NCT03410953; EudraCT-number 2016-004991-23). Funding: GRS 1360/A/16: Call for aid for the financing of research projects in biomedicine, health management and socio-health care to be developed in the centres of the Regional Health Management of Autonomous Community of Castile-Leon. In addition, this work has been supported by the Spanish Platform for Clinical Research and Clinical Trials, SCReN (Spanish Clinical Research Network), funded by the Subdirectorate General for Research Evaluation and Promotion of the Carlos III Health Institute (ISCIII), through the project PT13/0002/0039 and project PT17/0017/0023 integrated in the State Plan for R&D&I 2013–2016 and co-financed by and the European Regional Development Fund (ERDF)

Transiciones, conflictos y democracia : estudios de coyuntura

México ha vivido un largo proceso de transición que ha desencadenado dinamismos económicos, culturales y políticos. En la actual coyuntura, estos dinamismos muestran toda su complejidad, su inevitable articulación y la tensión entre las fuerzas que intentan sostener un viejo modelo de gobernar y decidir el rumbo del país, y aquellas que buscan abrirse a un espectro mucho más amplio y diversificado de actores. En ellos se conjuntan las aspiraciones más legítimas de los mexicanos por avanzar en el reconocimiento y respeto de la pluralidad étnica, de género y entre generaciones, y por impulsar una dinámica en la que —en medio de los procesos de mundialización— los distintos grupos e intereses de los mexicanos puedan ser incluidos. La transición mexicana tiende a centrarse en la dimensión política. La intensidad que cobran los procesos políticos y el énfasis que importantes analistas ponen en dichos procesos, contribuyen a que esta asociación vaya cobrandoíuerza. En este sentido, es necesario advertir que en las transiciones la tendencia privatizadora, la reducción del gasto social, así como la necesidad de pactos sociales que sean respetados, la participación creciente de la sociedad civil, etc. son factores importantes que, en medio de contradicciones, van generando nuevos esquemas de relación entre gobierno y sociedad.ITESO, A.C