Neuroprotective strategies against neonatal hypoxia-ischemia.

Motivation: Neonatal hypoxia ischemia (HI) is a brain damage caused by oxygen deprivation in newborns. Nowadays, it continues to be a major cause of neonatal mortality and lifelong neurodevelopmental disabilities worldwide.Neonatal HI physiopathology includes oxidative stress, inflammation, and apoptosis. Some studies have shown that nutraceuticals that have antioxidant, anti-inflammatory or anti-apoptotic properties can prevent neonatal HI by reducing brain damage. Thus, the aim of this work is to evaluate the neuroprotective potential of a plant-derived phenolic compound (PDPC) administered as a pre-treatment before the HI event, with focus on myelination and astroglia activation.Methods: Our group used the Rice-Vannucci mouse model of neonatal HI by ligating the left common carotid artery and then subjecting 7-day-old pups to hypoxia for 90 min. Pups were administered PDPC (at 20 or 100 mg/kg) or saline intraperitoneally 20 min before the intervention. Two days later, the brains were dissected, homogenized and stored at -80ºC for future experiments to evaluate the antioxidant potential of the PDPC. In a parallel study, seven days later, the brains were dissected to study myelination and astroglia activation by immunohistochemistry using MBP (myelin basic protein) and GFAP (glial fibrillary acidic protein) to assess the neuroprotective potential of PDPC.Results: Preliminary results indicate a loss of myelination in the ipsilateral hemispheres (where the carotid artery was ligated) of mice subjected to HI, but this loss seemed to be significantly reduced in a dose dependent manner in those mice pretreated with the PDPC. In the case of astroglia staining, experiments are still ongoing but these suggest an overexpression of astroglia in certain areas of the affected hemisphere of the brain in HI mice, such as the cortex or thalamus. We are currently stablishing an image analysis protocol to evaluate the overexpression of GFAP+ cells and observe if it lowers in the treated versus the non-treated group.Conclusions: To conclude, we can highlight that ongoing experiments suggest that pretreatment with PDPC, specially at 100 mg/kg, preserves myelination and may reduce astroglial activation. Future experiments will also evaluate the antioxidant potential of PDPC pretreatment by measuring the ROS production and the activity of antioxidant enzymes in brain homogenates

Detection of a G-Quadruplex as a Regulatory Element in Thymidylate synthase for Gene Silencing Using Polypurine Reverse Hoogsteen Hairpins

Thymidylate synthase (TYMS) enzyme is an anti-cancer target given its role in DNA biosynthesis. TYMS inhibitors (e.g., 5-Fluorouracil) can lead to drug resistance through an autoregulatory mechanism of TYMS that causes its overexpression. Since G-quadruplexes (G4) can modulate gene expression, we searched for putative G4 forming sequences (G4FS) in the TYMS gene that could be targeted using polypurine reverse Hoogsteen hairpins (PPRH). G4 structures in the TYMS gene were detected using the quadruplex forming G-rich sequences mapper and confirmed through spectroscopic approaches such as circular dichroism and NMR using synthetic oligonucleotides. Interactions between G4FS and TYMS protein or G4FS and a PPRH targeting this sequence (HpTYMS-G4-T) were studied by EMSA and thioflavin T staining. We identified a G4FS in the 5'UTR of the TYMS gene in both DNA and RNA capable of interacting with TYMS protein. The PPRH binds to its corresponding target dsDNA, promoting G4 formation. In cancer cells, HpTYMG-G4-T decreased TYMS mRNA and protein levels, leading to cell death, and showed a synergic effect when combined with 5-fluorouracil. These results reveal the presence of a G4 motif in the TYMS gene, probably involved in the autoregulation of TYMS expression, and the therapeutic potential of a PPRH targeted to the G4FS

MAGICA project: development of a Multi-frequency Automotive GNSS Integrated Cost effective Antenna

The present work describes the Multi-frequency Automotive GNSS Integrated Cost-effective Antenna (MAGICA) project and the first results. This is a two years project that started in August 2020 under the sponsorship of the European GNSS Agency (GSA) and within the framework of Fundamental Elements. The main objective of the project is to go beyond the state of the art. For the first time, it will provide a cost-effective high precision positioning antenna providing multi-frequency (L1/E1, L5/E5a/E5b & E6), multi-constellation (Galileo, GPS, BeiDou & GLONASS) characteristics, and phase stability as the most relevant performance features. Moreover, the antenna will be commercially ready to be integrated into a vehicle for Autonomous Driving operation. The proposed antenna will increase the number of frequency bands that are offered to the GNSS receivers of the vehicles today. It will include the E6 band of Galileo, providing, in this manner, not only more accurate but also safer positioning due to the authentication service.Peer ReviewedPostprint (published version

Human prefoldin modulates co-transcriptional pre-mRNA splicing.

Prefoldin is a heterohexameric complex conserved from archaea to humans that plays a cochaperone role during the co-translational folding of actin and tubulin monomers. Additional functions of prefoldin have been described, including a positive contribution to transcription elongation and chromatin dynamics in yeast. Here we show that prefoldin perturbations provoked transcriptional alterations across the human genome. Severe pre-mRNA splicing defects were also detected, particularly after serum stimulation. We found impairment of co-transcriptional splicing during transcription elongation, which explains why the induction of long genes with a high number of introns was affected the most. We detected genome-wide prefoldin binding to transcribed genes and found that it correlated with the negative impact of prefoldin depletion on gene expression. Lack of prefoldin caused global decrease in Ser2 and Ser5 phosphorylation of the RNA polymerase II carboxy-terminal domain. It also reduced the recruitment of the CTD kinase CDK9 to transcribed genes, and the association of splicing factors PRP19 and U2AF65 to chromatin, which is known to depend on CTD phosphorylation. Altogether the reported results indicate that human prefoldin is able to act locally on the genome to modulate gene expression by influencing phosphorylation of elongating RNA polymerase II, and thereby regulating co-transcriptional splicing.Ministerio de Ciencia e Innovación-Agencia Estatal de Investigación [BFU2016-77728-C3-1-P to S.C. and BFU2017-85420-R to J.C.R.] co-financed with European Union funds (FEDER); Andalusian Government [P12-BIO1938MO, BIO271, US-1256285 to S.C., BIO321 to J.C.R.]; Junta de Andalucía (to L.P.-B.). Funding for open access charge: Ministerio de Ciencia e Innovación-Agencia Estatal de Investigación [BFU2016-77728-C3-1-P]

Human prefoldin modulates co-transcriptional pre-mRNA splicing

Trabajo presentado en el IV Meeting RNALife, celebrado en Sevilla (España) del 12 al 13 de julio de 2021.Prefoldin is a heterohexameric complex conserved from archaea to humans that plays a co-chaperone role during the co-translational folding of actin and tubulin monomers. Additional functions of prefoldin have been described, including a positive contribution to transcription elongation and chromatin dynamics in yeast. Here we show that prefoldin perturbations provoked transcriptional alterations across the human genome. Severe pre-mRNA splicing defects were also detected, particularly after serum stimulation. We found impairment of co-transcriptional splicing during transcription elongation, which explains why the induction of long genes with a high number of introns was affected the most. We detected genome-wide prefoldin binding to transcribed genes and found that it correlated with the negative impact of prefoldin depletion on gene expression. Lack of prefoldin caused global decrease in Ser2 and Ser5 phosphorylation of the RNA polymerase II carboxy-terminal domain. It also reduced the recruitment of the CTD kinase CDK9 to transcribed genes, and the association of splicing factors PRP19 and U2AF65 to chromatin, which is known to depend on CTD phosphorylation. Altogether the reported results indicate that human prefoldin is able to act locally on the genome to modulate gene expression by influencing phosphorylation of elongating RNA polymerase II, and thereby regulating co-transcriptional splicing

Biomass-modulated fire dynamics during the last glacial-interglacial transition at the central pyrenees (Spain)

Understanding long-term fire ecology is essential for current day interpretation of ecosystem fire responses. However palaeoecology of fire is still poorly understood, especially at high-altitude mountain environments, despite the fact that these are fire-sensitive ecosystems and their resilience might be affected by changing fire regimes. We reconstruct wildfire occurrence since the Lateglacial (14.7. cal. ka BP) to the Mid-Holocene (6. cal. ka BP) and investigate the climate-fuel-fire relationships in a sedimentary sequence located at the treeline in the Central Spanish Pyrenees. Pollen, macro- and micro-charcoal were analysed for the identification of fire events (FE) in order to detect vegetation post-fire response and to define biomass-fire interactions. mean fire intervals (mfi) reduced since the Lateglacial, peaking at 9-7.7. cal. ka BP while from 7.7 to 6. cal. ka BP no fire is recorded. We hypothesise that Early Holocene maximum summer insolation, as climate forcing, and mesophyte forest expansion, as a fuel-creating factor, were responsible for accelerating fire occurrence in the Central Pyrenees treeline. We also found that fire had long-lasting negative effects on most of the treeline plant communities and that forest contraction from 7.7. cal. ka BP is likely linked to the ecosystem's threshold response to high fire frequencies.This research has been funded by the projects DINAMO (CGL2009-07992) (funding EGPF — grant ref. BES-2010-038593 and MSC), DINAMO2 (CGL2012-33063), ARAFIRE (2012 GA LC 064), GRACCIE-CONSOLIDER (CSD2007-00067). GGR was funded by the Juan de la Cierva Program (grant ref. JCI2009-04345) and JAE-Doc CSIC Program, LLM was supported by a postdoctoral MINT fellowship funded by the Institute for the Environment (Brunel University), AMC is a Ramón y Cajal fellow (ref: RYC-2008-02431), APS holds a grant funded by the Aragon Government (ref. 17030G/5423/480072/14003) and JAE holds a grant funded by the Basque Country Government (BFI-2010-5)

Cinco especies vegetales antiinflamatorias del Libellus de Medicinalibus Indorum Herbis de México, 1552: Una revisión botánica, química y farmacológica

Background and Aims: The Libellus de Medicinalibus Indorum Herbis (Little Book of the Medicinal Herbs of the Indians) includes 185 beautifully illustrated plants, 131 interpreted to species. Only some have been investigated regarding their attributed properties. Therefore, we selected six plants used as anti-inflammatories. The objectives of this work were to corroborate their botanical identity and to determine if contemporary chemical and pharmacological information supports their ancient therapeutic applications.Methods: The illustrations of the chosen plants were compared with specimens from the MEXU Herbarium to propose their possible taxonomic identity. The phytochemistry and anti-inflammatory activity of these species were reviewed in databases.Key results: The six plants selected from the Codex correspond to five species, since we consider that tetzmitl (Folium 13r) and texiyotl (Folium 22v) plants are the same species: Sedum dendroideum. Extracts from the leaves of S. dendroideum have shown anti-inflammatory activity in different pharmacological models due to derivatives of the flavonoid kaempferol, which supports its ancient medical applications to treat swollen face, eyes, and mouth. In Folium 48v, tzihuac copalli and tlacoecapatli are prescribed when “the vein punctured by the phlebotomy swells.” We agree they are Bursera bipinnata and Litsea glaucescens, respectively. To date, their possible anti-inflammatory properties have not been investigated, but other related species do present these. The Folium 22v recommends tememetla and tequixquiçacatl to relieve inflamed mouth. We corroborate that they are Echeveria gibbiflora and Distichlis spicata, respectively. These species do not have chemical-pharmacological studies.Conclusions: The bibliographic review suggests that anti-inflammatory properties attributed to S. dendroideum in the Codex have chemical and pharmacological support. Chemotaxonomic and pharmacological information suggests that B. bipinnata and L. glaucescens could bear these attributes and should be investigated experimentally. These three species are still used as anti-inflammatory in contemporary traditional medicine.Antecedentes y Objetivos: El Libellus de Medicinalibus Indorum Herbis (Librito de las Hierbas Medicinales de los Indios) incluye 185 plantas bellamente ilustradas, 131 interpretadas a especie. Solo algunas se han investigado respecto a las propiedades que ahí se les atribuyen. Por ello, seleccionamos seis plantas utilizadas como antiinflamatorias. Los objetivos de este trabajo fueron corroborar su identidad botánica y determinar si la información química y farmacológica contemporánea respalda sus antiguas aplicaciones terapéuticas.Métodos: Para proponer las especies a las cuales posiblemente corresponden las ilustraciones de las plantas elegidas, estas se compararon con especímenes del Herbario MEXU. Se revisó en bases de datos la fitoquímica y actividad antiinflamatoria de dichas especies.Resultados clave: Las seis plantas seleccionadas del códice corresponden a cinco especies, pues consideramos que las plantas tetzmitl (Folium 13r) y texiyotl (Folium 22v) son la misma especie: Sedum dendroideum. Los extractos de las hojas de S. dendroideum han presentado actividad antiinflamatoria en diferentes modelos farmacológicos debido a derivados del flavonoide kaempferol, lo cual respalda sus antiguas aplicaciones médicas para tratar la cara, ojos y boca hinchados. En el Folium 48v se prescriben tzihuac copalli y tlacoecapatli cuando “se hincha la vena pinchada por la flebotomía”. Concordamos en que son Bursera bipinnata y Litsea glaucescens, respectivamente. A la fecha, no se han investigado sus posibles propiedades antiinflamatorias, pero sí las presentan otras especies relacionadas. El Folium 22v recomienda tememetla y tequixquiçacatl para aliviar la boca inflamada. Corroboramos que son Echeveria gibbiflora y Distichlis spicata, respectivamente. Dichas especies no cuentan con estudios químico-farmacológicos.Conclusiones: La revisión bibliográfica sugiere que las propiedades antiinflamatorias atribuidas en el Códice para S. dendroideum tienen sustento químico y farmacológico. La información quimiotaxonómica y farmacológica sugiere que B. bipinnata y L. glaucescens podrían presentarlas y deben investigarse experimentalmente. Estas tres especies aún se emplean como antiinflamatorias en la medicina tradicional contemporánea

Accuracy and Survival Outcomes after National Implementation of Sentinel Lymph Node Biopsy in Early Stage Endometrial Cancer

Background. Sentinel lymph node (SLN) biopsy has recently been accepted to evaluate nodal status in endometrial cancer at early stage, which is key to tailoring adjuvant treatments. Our aim was to evaluate the national implementation of SLN biopsy in terms of accuracy to detect nodal disease in a clinical setting and oncologic outcomes according to the volume of nodal disease. Patients and Methods. A total of 29 Spanish centers participated in this retrospective, multicenter registry including patients with endometrial adenocarcinoma at preoperative early stage who had undergone SLN biopsy between 2015 and 2021. Each center collected data regarding demographic, clinical, histologic, therapeutic, and survival characteristics. Results. A total of 892 patients were enrolled. After the surgery, 12.9% were suprastaged to FIGO 2009 stages III-IV and 108 patients (12.1%) had nodal involvement: 54.6% macrometastasis, 22.2% micrometastases, and 23.1% isolated tumor cells (ITC). Sensitivity of SLN biopsy was 93.7% and false negative rate was 6.2%. After a median follow up of 1.81 years, overall surivial and disease-free survival were significantly lower in patients who had macrometastases when compared with patients with negative nodes, micrometastases or ITC. Conclusions. In our nationwide cohort we obtained high sensitivity of SLN biopsy to detect nodal disease. The oncologic outcomes of patients with negative nodes and low-volume disease were similar after tailoring adjuvant treatments. In total, 22% of patients with macrometastasis and 50% of patients with micrometastasis were at low risk of nodal metastasis according to their preoperative risk factors, revealing the importance of SLN biopsy in the surgical management of patients with early stage EC

Universidad y sociedad: comunicación e integración en empresas e instituciones públicas y organizaciones no lucrativas. Nuevos avances

Depto. de Teorías y Análisis de la ComunicaciónFac. de Ciencias de la InformaciónFALSEsubmitte

Grupo español de cirugía torácica asistida por videoimagen: método, auditoría y resultados iniciales de una cohorte nacional prospectiva de pacientes tratados con resecciones anatómicas del pulmón

Introduction: our study sought to know the current implementation of video-assisted thoracoscopic surgery (VATS) for anatomical lung resections in Spain. We present our initial results and describe the auditing systems developed by the Spanish VATS Group (GEVATS). Methods: we conducted a prospective multicentre cohort study that included patients receiving anatomical lung resections between 12/20/2016 and 03/20/2018. The main quality controls consisted of determining the recruitment rate of each centre and the accuracy of the perioperative data collected based on six key variables. The implications of a low recruitment rate were analysed for '90-day mortality' and 'Grade IIIb-V complications'. Results: the series was composed of 3533 cases (1917 VATS; 54.3%) across 33 departments. The centres' median recruitment rate was 99% (25-75th:76-100%), with an overall recruitment rate of 83% and a data accuracy of 98%. We were unable to demonstrate a significant association between the recruitment rate and the risk of morbidity/mortality, but a trend was found in the unadjusted analysis for those centres with recruitment rates lower than 80% (centres with 95-100% rates as reference): grade IIIb-V OR=0.61 (p=0.081), 90-day mortality OR=0.46 (p=0.051). Conclusions: more than half of the anatomical lung resections in Spain are performed via VATS. According to our results, the centre's recruitment rate and its potential implications due to selection bias, should deserve further attention by the main voluntary multicentre studies of our speciality. The high representativeness as well as the reliability of the GEVATS data constitute a fundamental point of departure for this nationwide cohort