Characterisation of neuronal and glial populations of the visual system during zebrafish lifespan

[EN] During visual system morphogenesis, several cell populations arise at different time points correlating with the expression of specific molecular markers We have analysed the distribution pattern of three molecular markers (zn-1, calretinin and glial fibrillary acidic protein) which are involved in the development of zebrafish retina and optic tectum. Zn-1 is a neural antigen expressed in the developing zebrafish central nervous system. Calretinin is the first calcium-binding protein expressed in the central nervous system of vertebrates and it is widely distributed in different neuronal populations of vertebrate retina, being a valuable marker for its early and late development. Glial fibrillary acidic protein (GFAP), which is an astroglial marker, is a useful tool for characterising the glial environment in which the optic axons develop. We describe the expression profile changes in these three markers throughout the zebrafish lifespan with special attention to ganglion cells and their projections. Zn-1 is expressed in the first postmitotic ganglion cells of the retina. Calretinin is observed in the ganglion and amacrine cells of the retina in neurons of different tectal bands and in axons of retinofugal projections. GFAP is localised in the endfeet of Müller cells and in radial processes of the optic tectum after hatching. A transient expression of GFAP in the optic nerve, coinciding with the arrival of the first calretinin-immunoreactive optic axons, is observed. As axonal growth occurs in these regions of the zebrafish visual pathway (retina and optic tectum)throughout the lifespan, a relationship between GFAP expression and the correct arrangement of the first optic axons may exist. In conclusion we provide valuable neuroanatomical data about the best characterised sensorial pathway to be used in further studies such as teratology and toxicology

El aprovechamiento de la campiña entre Teba y Ardales (Málaga) por los agricultores del Neolítico: el caso del Cerro de la Higuera

Durante la construcción del parque eólico “La Higuera”, en los términos municipales de Teba y Ardales (Málaga) se localizaron, al aire libre, productos arqueológicos prehistóricos que han permitido analizar lo que fue un asentamiento de agricultores del Neolítico

Geomorphological record of extreme wave events during Roman times in the Guadalquivir estuary (gulf of cadiz, SW Spain): An archaeological and paleogeographical approach

Analysis of the geological record has made it possible to delimit for theGuadalquivir estuary the traces of extreme wave events (EWEs) during the Roman period in the Iberian Peninsula (218 BCE to 476 CE). The largest event occurred in the 2nd-3rd century CE. It generated clearly visible erosive effects in the coastal barriers, including washover fans and erosional scarps. In the inner estuary, however, the effects were minor: crevasse splays that broke levees and cheniers, as well as a residual sedimentary lag. The significant development of the spits protected the inner estuary from the marine incursion, which only caused a water level rise with low-regime waves. Correlation of the geomorphological and sedimentary marks left by this event with the archaeological and geological evidence of other events recognized elsewhere in the Gulf of Cadiz effectively argues for a tsunami as to the nature of the 2nd-3rd century CE event. Yet this and the other identified EWEs in the Guadalquivir estuary during the pre-Roman and the Roman period all fit a model of paleogeographic evolution dominated by processes of coastal progradation and estuarine infilling. Radiocarbon dating, geomorphological analysis, and historical references fail to warrant the so-called '218-209 BCE' Atlantic tsunami, as hypothesized in the received scientific literature. In pre-Roman and Roman times, human occupation at the mouth of the Guadalquivir River was strongly influenced by various geodynamic processes, the location of the settlements being contingent upon dependable, fast communication with the sea and, above all, upon adequate protection from EWEs, on the leeward side of spits. Progressive progradation of these coastal barriers combined with the gradual infilling of the estuary to make navigation to open sea increasingly difficult and, eventually, to result in the abandonment of settlements

Antiretroviral therapy duration and immunometabolic state determine efficacy of ex vivo dendritic cell-based treatment restoring functional HIV-specific CD8+ T cells in people living with HIV.

Dysfunction of CD8+ T cells in people living with HIV-1 (PLWH) receiving anti-retroviral therapy (ART) has restricted the efficacy of dendritic cell (DC)-based immunotherapies against HIV-1. Heterogeneous immune exhaustion and metabolic states of CD8+ T cells might differentially associate with dysfunction. However, specific parameters associated to functional restoration of CD8+ T cells after DC treatment have not been investigated. We studied association of restoration of functional HIV-1-specific CD8+ T cell responses after stimulation with Gag-adjuvant-primed DC with ART duration, exhaustion, metabolic and memory cell subsets profiles. HIV-1-specific CD8+ T cell responses from a larger proportion of PLWH on long-term ART (more than 10 years; LT-ARTp) improved polyfunctionality and capacity to eliminate autologous p24+ infected CD4+ T cells in vitro. In contrast, functional improvement of CD8+ T cells from PLWH on short-term ART (less than a decade; ST-ARTp) after DC treatment was limited. This was associated with lower frequencies of central memory CD8+ T cells, increased co-expression of PD1 and TIGIT and reduced mitochondrial respiration and glycolysis induction upon TCR activation. In contrast, CD8+ T cells from LT-ARTp showed increased frequencies of TIM3+ PD1- cells and preserved induction of glycolysis. Treatment of dysfunctional CD8+ T cells from ST-ARTp with combined anti-PD1 and anti-TIGIT antibodies plus a glycolysis promoting drug restored their ability to eliminate infected CD4+ T cells. Together, our study identifies specific immunometabolic parameters for different PLWH subgroups potentially useful for future personalized DC-based HIV-1 vaccines. NIH (R21AI140930), MINECO/FEDER RETOS (RTI2018-097485-A-I00) and CIBERINF grants.NIH (R21AI140930), MINECO/FEDER RETOS (RTI2018-097485-A-I00) and CIBERINF grants. We would like to thank the NIH AIDS Reagent Pro- gram, Division of AIDS, NIAID, NIH for providing HIV-1 PTE Gag Peptide Pool from NIAID, DAIDS (cat #11057) for the study. We would also like to thank Alvaro Serrano Navarro, for his help on adapting the lin- ear mixed model previously described by Martin- C ofreces N. et al83 to our data. Graphical schematic rep- resentations were created with BioRender.com. EMG was supported by the NIH R21 program (R21AI140930), the Ramón y Cajal Program (RYC2018- 024374-I), the MINECO/FEDER RETOS program (RTI2018-097485-A-I00), by Comunidad de Madrid Talento Program (2017-T1/BMD-5396) and by Gilead becas de investigaci on (GLD19/00168). EMG and IDS are supported by Centro de Investigación Biomédica en Red (CIBERINF) de Enfermedades Infecciosas (CB21/ 13/00107). MCM was supported by NIH R21 program (R21AI140930), “La Caixa Banking Foundation (H20- 00218) and Gilead becas de investigaci on (GLD19/ 00168). MJB is supported by the Miguel Servet program funded by the Spanish Health Institute Carlos III (CP17/00179), the MINECO/FEDER RETOS program (RTI2018-101082-B-100), and Fundació La Marat o TV3 (201805-10FMTV3). EMG and MJB are both funded by “La Caixa Banking Foundation (H20-00218) and by REDINCOV grant from Fundació La Marat o TV3. FSM was supported by SAF2017-82886-R and PDI-2020- 120412RB-I00 grants from the Ministerio de Ciencia e Innovaci on, and HR17-00016 grant from “La Caixa Banking Foundation. HF was funded by PI21/01583 grant from Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III. MJC was supported by PID2019- 104406RB-I00 from Ministerio de Ciencia e Innovación. ISC was funded by the CM21/00157 Rio- Hortega grant. IT was supported by grant for the pro- motion of research studies master-UAM 2021.S

Educafarma 5.0: continuación y mejora de un programa de formación continuada de profesores y estudiantes de la Facultad de Farmacia con recursos propios

Memoria ID-0103. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2016-2017

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Antiretroviral therapy duration and immunometabolic state determine efficacy of ex vivo dendritic cell-based treatment restoring functional HIV-specific CD8+ T cells in people living with HIV

Dysfunction of CD8 + T cells in people living with HIV-1 (PLWH) receiving anti-retroviral therapy (ART) has restricted the efficacy of dendritic cell (DC)-based immunotherapies against HIV-1. Heterogeneous immune exhaustion and metabolic states of CD8 + T cells might differentially associate with dysfunction. However, specific parameters associated to functional restoration of CD8 + T cells after DC treatment have not been investigated. We studied association of restoration of functional HIV-1-specific CD8 + T cell responses after stimulation with Gag-adjuvant-primed DC with ART duration, exhaustion, metabolic and memory cell subsets profiles. HIV-1-specific CD8 + T cell responses from a larger proportion of PLWH on long-term ART (more than 10 years; LT-ARTp) improved polyfunctionality and capacity to eliminate autologous p24 + infected CD4 + T cells in vitro. In contrast, functional improvement of CD8 + T cells from PLWH on short-term ART (less than a decade; ST-ARTp) after DC treatment was limited. This was associated with lower frequencies of central memory CD8 + T cells, increased co-expression of PD1 and TIGIT and reduced mitochondrial respiration and glycolysis induction upon TCR activation. In contrast, CD8 + T cells from LT-ARTp showed increased frequencies of TIM3 + PD1 − cells and preserved induction of glycolysis. Treatment of dysfunctional CD8 + T cells from ST-ARTp with combined anti-PD1 and anti-TIGIT antibodies plus a glycolysis promoting drug restored their ability to eliminate infected CD4 + T cells. Together, our study identifies specific immunometabolic parameters for different PLWH subgroups potentially useful for future personalized DC-based HIV-1 vaccines. NIH (R21AI140930), MINECO/FEDER RETOS (RTI2018-097485-A-I00) and CIBERINF grants

Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C : A prospective observational study

Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C. In a prospective observational cohort study, incorporating a retrospective determination of NP-C SI scores, two different diagnostic approaches were applied in two separate groups of unrelated patients from 51 Spanish medical centers (n = 118 in both groups). From Jan 2010 to Apr 2012 (Period 1), patients with ≥2 clinical signs/symptoms of NP-C were considered 'suspected NP-C' cases, and NPC1/NPC2 sequencing, plasma chitotriosidase (ChT), CCL18/PARC and sphingomyelinase levels were assessed. Based on findings in Period 1, plasma ChT and CCL18/PARC, and NP-C SI prediction scores were determined in a second group of patients between May 2012 and Apr 2014 (Period 2), and NPC1 and NPC2 were sequenced only in those with elevated ChT and/or elevated CCL18/PARC and/or NP-C SI ≥70. Filipin staining and 7-ketocholesterol (7-KC) measurements were performed in all patients with NP-C gene mutations, where possible. In total across Periods 1 and 2, 10/236 (4%) patients had a confirmed diagnosis o NP-C based on gene sequencing (5/118 [4.2%] in each Period): all of these patients had two causal NPC1 mutations. Single mutant NPC1 alleles were detected in 8/236 (3%) patients, overall. Positive filipin staining results comprised three classical and five variant biochemical phenotypes. No NPC2 mutations were detected. All patients with NPC1 mutations had high ChT activity, high CCL18/PARC concentrations and/or NP-C SI scores ≥70. Plasma 7-KC was higher than control cut-off values in all patients with two NPC1 mutations, and in the majority of patients with single mutations. Family studies identified three further NP-C patients. This approach may be very useful for laboratories that do not have mass spectrometry facilities and therefore, they cannot use other NP-C biomarkers for diagnosis