Chemical-physical characterization of isolated plant cuticles subjected to low-dose γ-irradiation

Isolated tomato fruit cuticles were subjected to low dose (80 Gy) γ-irradiation, as a potential methodology to prevent harvested fruit and vegetables spoilage. Both irradiated and non-irradiated samples have been morphologically and chemically characterized by scanning electron (SEM), atomic force (AFM), attenuated total reflectance Fourier transform infrared (ATR-FTIR) and X-ray photoelectron (XPS) spectroscopies. Additionally, electrochemical measurements comprising membrane potential and diffusive permeability were carried out to detect modifications in transport properties of the cuticle as the fruit primary protective membrane. It has been found that low dose γ-irradiation causes some textural changes on the surface but no significant chemical modification. Texture modification is found to be due to a partial removal of outermost (epicuticular) waxes which is accompanied by mild changes of electrochemical parameters such as the membrane fixed charge, cation transport number and salt permeability. The modification of such parameters indicates a slight reduction of the barrier properties of the cuticle upon low dose γ-irradiation.

Multiciliated ependyma recovery through a sequential cell therapy in posthemorrhagic hydrocephalus.

Posthemorrhagic hydrocephalus (PHH) is a significant cause for premature children’s morbidity, mortality, and peri/postnatal neurodevelopmental impairment. PHH is mainly triggered by germinal matrix hemorrhages (GMH) and causes germinal matrix and ependyma disfunction. Ependyma constitutes a relevant tissue barrier with roles in cerebrospinal fluid homeostasis, circulation, and neurogenesis, hence situating ependyma as a main target when treating PHH. Clinical treatments are directed to eliminate immediate inflammatory condition triggered by the bleeding, to drain excess of CSF if needed, but not to treat or recover ependyma structure. Ependymal progenitors were obtained from P0 mice. Cells were cultured under specific conditions to enhance either ependymal proliferation or differentiation status. Different GMH/IVH neuroinflammatory conditions were mimed in the ependyma cultures, different stem cell therapies tested and effect on the ependymal differentiation measured. Additionally, ventricular wall explants from mice with induced PHH were obtained and cultured as ex-vivo system of PHH. A combination of stem cells was applied on the tissue to probe its regenerative capabilities on the multiciliated ependyma. All samples were analyzed through immunofluorescence and laser confocal microscopy and quantified. Results show that (i) ependymal progenitors’ maturation is hindered under neuroinflammatory conditions, showing no multiciliated ependyma and (ii) the tested stem cell combination promotes ependymal progenitors’ survival albeit does not alter the differentiation of the selfsame. In summary, it can be stated that the final differentiation of the ependyma is disrupted by the molecular conditions triggered by GMH/IVH, which our proposed cell therapy is able to counteract through increased survival and differentiation in a murine model of experimental PHHJunta de Andalucia (UMA18-FEDERJA-277) and Instituto de Salud Carlos III (PI19/00778), Spain; co-financed by FEDER funds from the European Union, Spain. Also, II-PPITD, Universidad de Malaga, Spain (to JL-dSS); and I-PPITD, Universidad de Málaga, Spain (to LMR-P) Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Testing exosomes as a treatment for posthemorrhagic hydrocephalus.

Germinal matrix hemorrhages and intraventricular hemorrhages (GMH/IVH) lead to posthemorrhagic hydrocephalus (PHH), a severe cause of morbidity and mortality in premature neonates. GMH/IVH disrupts the ependyma, which forms a physical and functional barrier between the brain parenchyma and the cerebrospinal fluid (CSF). CSF circulation and physiology is also affected by ependyma disruption. Thus, ependyma is a key target when designing PHH treatments. Despite this, hydrocephalus treatments are surgical and focused on alleviating ventricular pressure by draining CSF. No therapy is currently aimed to recover the ependyma. Nevertheless, bone marrow derived mesenchymal stem cells (MSCs) are known to be great agents when dealing with inflammation. Also, exosomes have proven to be promising tools when designing anti-inflammatory treatments. Therefore, gaining insight in the treating capabilities of MSCs exosomes in PHH can be valuable. Results Differential effects in edema progression and ependymal cells ciliogenesis are found when analyzing treatments with conditioned and non-conditioned exosomes in moderate PHH and severe PHH.- Universidad de Malaga. Campus de Excelencia Internacional Andalucia Tech. - Junta de Andalucia (UMA18-FEDERJA-277) - Instituto de Salud Carlos III (PI19/00778) - Cofinanciado por fondos FEDER - UE

Generation of periventricular reactive astrocytes overexpressing aquaporin 4 Is stimulated by mesenchymal stem cell therapy

Aquaporin-4 (AQP4) plays a crucial role in brain water circulation and is considered a therapeutic target in hydrocephalus. Congenital hydrocephalus is associated with a reaction of astrocytes in the periventricular white matter both in experimental models and human cases. A previous report showed that bone marrow-derived mesenchymal stem cells (BM-MSCs) transplanted into the lateral ventricles of hyh mice exhibiting severe congenital hydrocephalus are attracted by the periventricular astrocyte reaction, and the cerebral tissue displays recovery. The present investigation aimed to test the effect of BM-MSC treatment on astrocyte reaction formation. BM-MSCs were injected into the lateral ventricles of four-day-old hyh mice, and the periventricular reaction was detected two weeks later. A protein expression analysis of the cerebral tissue differentiated the BM-MSC-treated mice from the controls and revealed effects on neural development. In in vivo and in vitro experiments, BM-MSCs stimulated the generation of periventricular reactive astrocytes overexpressing AQP4 and its regulatory protein kinase D-interacting substrate of 220 kDa (Kidins220). In the cerebral tissue, mRNA overexpression of nerve growth factor (NGF), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 (HIF1α), and transforming growth factor beta 1 (TGFβ1) could be related to the regulation of the astrocyte reaction and AQP4 expression. In conclusion, BM-MSC treatment in hydrocephalus can stimulate a key developmental process such as the periventricular astrocyte reaction, where AQP4 overexpression could be implicated in tissue recovery.The present work was supported by grants PI15/00619 and PI19/00778 (to A.J.J. and P.P.-G.), PI21/000914 (to J.V.) and PI21/000915 (to A.G.) from the Instituto de Salud Carlos III, Spain, co-financed by FEDER funds from the European Union; PI18-RT-2233 from Junta de Andalucía (to A.G.) co-financed by Programa Operativo FEDER 2014–2020; PID2020-115218RB-I00 to T.I., funded by MCIN/AEI/10.13039/501100011033; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED, Instituto de Salud Carlos III, Spain) to J.V., T.I. and A.G.; FPU13/02906 to MG-B from the Ministerio de Educación, Cultura y Deporte, Spain; RYC-2014-16980 to P.P.-G. from the Ministerio de Economía y Competitividad, Spain; UMA18-FEDERJA-277 from Plan Operativo FEDER Andalucía 2014–2020 and Universidad de Málaga to P.P.-G.; Proyectos dirigidos por jóvenes investigadores from Universidad de Málaga to P.P.-G. The cost of this publication has been paid in art by “ERDF A way of making Europe” funds. Partial funding for open access charge: Universidad de Málaga

Common Variation in the PIN1 Locus Increases the Genetic Risk to Suffer from Sertoli Cell-Only Syndrome

We aimed to analyze the role of the common genetic variants located in the PIN1 locus, a relevant prolyl isomerase required to control the proliferation of spermatogonial stem cells and the integrity of the blood–testis barrier, in the genetic risk of developing male infertility due to a severe spermatogenic failure (SPGF). Genotyping was performed using TaqMan genotyping assays for three PIN1 taggers (rs2287839, rs2233678 and rs62105751). The study cohort included 715 males diagnosed with SPGF and classified as suffering from non-obstructive azoospermia (NOA, n = 505) or severe oligospermia (SO, n = 210), and 1058 controls from the Iberian Peninsula. The allelic frequency differences between cases and controls were analyzed by the means of logistic regression models. A subtype specific genetic association with the subset of NOA patients classified as suffering from the Sertoli cell-only (SCO) syndrome was observed with the minor alleles showing strong risk effects for this subset (ORaddrs2287839 = 1.85 (1.17–2.93), ORaddrs2233678 = 1.62 (1.11–2.36), ORaddrs62105751 = 1.43 (1.06–1.93)). The causal variants were predicted to affect the binding of key transcription factors and to produce an altered PIN1 gene expression and isoform balance. In conclusion, common non-coding single-nucleotide polymorphisms located in PIN1 increase the genetic risk to develop SCO.Plan Andaluz de Investigacion, Desarrollo e Innovacion (PAIDI 2020) PY20_00212 P20_00583Spanish Ministry of Economy and Competitiveness through the Spanish National Plan for Scientific and Technical Research and Innovation SAF2016-78722-R PID2020-120157RB-I00Proyectos I + D + i del Programa Operativo FEDER 2020 B-CTS-584-UGR20 B-CTS-260-UGR20Spanish Government RYC-2014-16458Spanish Ministry of Economy and Competitiveness through the "Juan de la Cierva Incorporacion" program (MCIN/AEI) IJC2018038026-IEuropean CommissionMCIN/AEIFSE "El FSE invierte en tu futuro" FPU20/02926 BES-2017-081222Portuguese Foundation for Science and Technology (FCT) - European Social Funds (COMPETE-FEDER) Portuguese Foundation for Science and Technology IF/01262/2014FCT from the Portuguese State Budget of the Ministry for Science, Technology and High Education SFRH/BPD/120777/2016European Social Fund through the Programa Operacional do Capital HumanoPortuguese Foundation for Science and Technology European Commission UID/BIM/00009/2013 UIDB/UIDP/00009/2020Instituto de Salud Carlos III (FEDER funds/European Regional Development Fund (ERDF)-a way to build Europe) DTS18/00101Generalitat de Catalunya 2017SGR191SNS-Dpt. Salut Generalitat de Catalunya CES09/020 MCIN/AEI BES-2017-081222 PEstC/SAU/LA0003/2013 POCI-01-0145-FEDER-00727

Long-term effects of coronavirus disease 2019 on the cardiovascular system, CV COVID registry: A structured summary of a study protocol

Background: Patients presenting with the coronavirus-2019 disease (COVID-19) may have a high risk of cardiovascular adverse events, including death from cardiovascular causes. The long-term cardiovascular outcomes of these patients are entirely unknown. We aim to perform a registry of patients who have undergone a diagnostic nasopharyngeal swab for SARS-CoV-2 and to determine their long-term cardiovascular outcomes. Study and design: This is a multicenter, observational, retrospective registry to be conducted at 17 centers in Spain and Italy (ClinicalTrials.gov number: NCT04359927). Consecutive patients older than 18 years, who underwent a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV2 in the participating institutions, will be included since March 2020, to August 2020. Patients will be classified into two groups, according to the results of the RT-PCR: COVID-19 positive or negative. The primary outcome will be cardiovascular mortality at 1 year. The secondary outcomes will be acute myocardial infarction, stroke, heart failure hospitalization, pulmonary embolism, and serious cardiac arrhythmias, at 1 year. Outcomes will be compared between the two groups. Events will be adjudicated by an independent clinical event committee. Conclusion: The results of this registry will contribute to a better understanding of the long-term cardiovascular implications of the COVID19

Instantaneous Wave-Free Ratio for the Assessment of Intermediate Left Main Coronary Artery Stenosis: Correlations With Fractional Flow Reserve/Intravascular Ultrasound and Prognostic Implications: The iLITRO-EPIC07 Study

Background: There is little information available on agreement between fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) in left main coronary artery (LMCA) intermediate stenosis. Besides, several meta-analyses support the use of FFR to guide LMCA revascularization, but limited information is available on iFR in this setting. Our aims were to establish the concordance between FFR and iFR in intermediate LMCA lesions, to evaluate with intravascular ultrasound (IVUS) in cases of FFR/iFR discordance, and to prospectively validate the safety of deferring revascularization based on a hybrid decision-making strategy combining iFR and IVUS. Methods: Prospective, observational, multicenter registry with 300 consecutive patients with intermediate LMCA stenosis who underwent FFR and iFR and, in case of discordance, IVUS and minimal lumen area measurements. Primary clinical end point was a composite of cardiovascular death, LMCA lesion-related nonfatal myocardial infarction, or unplanned LMCA revascularization. Results: FFR and iFR had an agreement of 80% (both positive in 67 and both negative in 167 patients); in case of disagreement (31 FFR+/iFR- and 29 FFR-/iFR+) minimal lumen area was & GE;6 mm(2) in 8.7% of patients with FFR+ and 14.6% with iFR+. Among the 300 patients, 105 (35%) underwent revascularization and 181 (60%) were deferred according to iFR and IVUS. At a median follow-up of 20 months, major adverse cardiac events incidence was 8.3% in the defer group and 13.3% in the revascularization group (hazard ratio, 0.71 [95% CI 0.30-1.72]; P=0.45). Conclusions: In patients with intermediate LMCA stenosis, a physiology-guided treatment decision is feasible either with FFR or iFR with moderate concordance between both indices. In case of disagreement, the use of IVUS may be useful to indicate revascularization. Deferral of revascularization based on iFR appears to be safe in terms of major adverse cardiac events

Common genetic variation in KATNAL1 non-coding regions is involved in the susceptibility to severe phenotypes of male infertility

Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9546047/Background: Previous studies in animal models evidenced that genetic mutations of KATNAL1, resulting in dysfunction of its encoded protein, lead to male infertility through disruption of microtubule remodelling and premature germ cell exfoliation. Subsequent studies in humans also suggested a possible role of KATNAL1 single nucleotide polymorphisms in the development of male infertility as a consequence of severe spermatogenic failure. Objectives: The main objective of the present study is to evaluate the effect of the common genetic variation of KATNAL1 in a large and phenotypically well-characterised cohort of infertile men because of severe spermatogenic failure. Materials and methods: A total of 715 infertile men because of severe spermato genic failure, including 210 severe oligospermia and 505 non-obstructive azoospermia patients, as well as 1058 unaffected controls were genotyped for three KATNAL1 single-nucleotide polymorphism taggers (rs2077011, rs7338931 and rs2149971). Case–control association analyses by logistic regression assuming different models and in silico functional characterisation of risk variants were conducted. Results: Genetic associations were observed between the three analysed taggers and different severe spermatogenic failure groups. However, in all cases, the haplotype model (rs2077011*C | rs7338931*T | rs2149971*A) better explained the observed associations than the three risk alleles independently. This haplotype was associated with non-obstructive azoospermia (adjusted p = 4.96E-02, odds ratio = 2.97), Sertoli cell only syndrome (adjusted p = 2.83E-02, odds ratio = 5.16) and testicular sperm extraction unsuccessful outcomes (adjusted p = 8.99E-04, odds ratio = 6.13). The in silico analyses indicated that the effect on severe spermatogenic failure predisposition could be because of an alteration of the KATNAL1 splicing pattern. Conclusions: Specific allelic combinations of KATNAL1 genetic polymorphisms may confer a risk of developing severe male infertility phenotypes by favouring the overrepresentation of a short non-functional transcript isoform in the testis.This work was supported by the Spanish Ministry of Economy and Competitiveness through the Spanish National Plan for Scientific and Technical Research and Innovation (refs. SAF2016-78722-R and PID2020-120157RB-I00), the ‘Instituto de Salud Carlos III’ (Fondo de Investigaciones Sanitarias)/Fondo Europeo de Desarrollo Regional ‘Una manera de hacer Europa’ (FIS/FEDER) (ref. DTS18/00101 to Sara Larriba), the Generalitat de Catalunya (ref. 2017SGR191), the ‘Ramón y Cajal’ program (ref. RYC-2014-16458) and the ‘Juan de la Cierva Incorporación’ program (ref. IJC2018-038026-I), as well as the Andalusian Government through the R&D&i Projects Grants for Universities and Public Research Entities (ref. PY20_00212), which include FEDER funds. Andrea Guzmán-Jiménez was a recipient of a grant from the Spanish Ministry of Education and Professional Training (‘Becas de Colaboración en Departamentos Universitarios para el curso académico 2020/2021’). Patricia I. Marques is supported by the FCT post-doctoral fellowship (SFRH/BPD/120777/2016), financed from the Portuguese State Budget of the Ministry for Science, Tech nology and High Education and from the European Social Fund, available through the ‘Programa Operacional do Capital Humano’. João Gonçalves was partially funded by FCT/MCTES through national funds attributed to the Centre for Toxicogenomics and Human Health— ToxOmics (UID/BIM/00009/2016 and UIDB/00009/2020). Sara Larriba is sponsored by the Researchers Consolidation Program (ISCIII SNS/Dpt. Salut Generalitat de Catalunya) (CES09/020).info:eu-repo/semantics/publishedVersio

Common genetic variation in KATNAL1 non‐coding regions is involved in the susceptibility to severe phenotypes of male infertility

© 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.Background: Previous studies in animal models evidenced that genetic mutations of KATNAL1, resulting in dysfunction of its encoded protein, lead to male infertility through disruption of microtubule remodelling and premature germ cell exfoliation. Subsequent studies in humans also suggested a possible role of KATNAL1 single-nucleotide polymorphisms in the development of male infertility as a consequence of severe spermatogenic failure. Objectives: The main objective of the present study is to evaluate the effect of the common genetic variation of KATNAL1 in a large and phenotypically well-characterised cohort of infertile men because of severe spermatogenic failure. Materials and methods: A total of 715 infertile men because of severe spermatogenic failure, including 210 severe oligospermia and 505 non-obstructive azoospermia patients, as well as 1058 unaffected controls were genotyped for three KATNAL1 single-nucleotide polymorphism taggers (rs2077011, rs7338931 and rs2149971). Case-control association analyses by logistic regression assuming different models and in silico functional characterisation of risk variants were conducted. Results: Genetic associations were observed between the three analysed taggers and different severe spermatogenic failure groups. However, in all cases, the haplotype model (rs2077011*C | rs7338931*T | rs2149971*A) better explained the observed associations than the three risk alleles independently. This haplotype was associated with non-obstructive azoospermia (adjusted p = 4.96E-02, odds ratio = 2.97), Sertoli-cell only syndrome (adjusted p = 2.83E-02, odds ratio = 5.16) and testicular sperm extraction unsuccessful outcomes (adjusted p = 8.99E-04, odds ratio = 6.13). The in silico analyses indicated that the effect on severe spermatogenic failure predisposition could be because of an alteration of the KATNAL1 splicing pattern. Conclusions: Specific allelic combinations of KATNAL1 genetic polymorphisms may confer a risk of developing severe male infertility phenotypes by favouring the overrepresentation of a short non-functional transcript isoform in the testis.This work was supported by the Spanish Ministry of Economy and Competitiveness through the Spanish National Plan for Scientific and Technical Research and Innovation (refs. SAF2016-78722-R and PID2020-120157RB-I00), the ‘Instituto de Salud Carlos III’ (Fondo de Investigaciones Sanitarias)/Fondo Europeo de Desarrollo Regional ‘Una manera de hacer Europa’ (FIS/FEDER) (ref. DTS18/00101 to Sara Larriba), the Generalitat de Catalunya (ref. 2017SGR191), the ‘Ramón y Cajal’ program (ref. RYC-2014-16458) and the ‘Juan de la Cierva Incorporación’ program (ref. IJC2018-038026-I), as well as the Andalusian Government through the R&D&i Projects Grants for Universities and Public Research Entities (ref. PY20_00212), which include FEDER funds. Andrea Guzmán-Jiménez was a recipient of a grant from the Spanish Ministry of Education and Professional Training (‘Becas de Colaboración en Departamentos Universitarios para el curso académico 2020/2021’). Patricia I. Marques is supported by the FCT post-doctoral fellowship (SFRH/BPD/120777/2016), financed from the Portuguese State Budget of the Ministry for Science, Technology and High Education and from the European Social Fund, available through the ‘Programa Operacional do Capital Humano’. João Gonçalves was partially funded by FCT/MCTES through national funds attributed to the Centre for Toxicogenomics and Human Health—ToxOmics (UID/BIM/00009/2016 and UIDB/00009/2020). Sara Larriba is sponsored by the Researchers Consolidation Program (ISCIII SNS/Dpt. Salut Generalitat de Catalunya) (CES09/020).info:eu-repo/semantics/publishedVersio

Casos de estudio en México y Latinoamérica

Ante la presencia de conflictos sociales y territoriales, las comunidades organizadas buscan estrategias de solución y confrontación. Es el estudio de dichos movimientos, lo que motiva a la publicación de éste libro: Respuestas comunitarias ante conflictos ambientales. Casos de estudio en México y Latinoamérica, reúne catorce textos que analizan las respuestas sociales y documentan la acción colectiva de comunidades que se han organizado para autogestionar soluciones ante conflictos territoriales, económicos y ambientales, en su propio entorno. Las aportaciones de investigadores y activistas, desde enfoques teóricos y metodológicos particulares, exponen casos de estudio sobre organizaciones formales e informales que se han conformado para afrontar los retos que representan proyectos productivos como fábricas cementeras, mineras, puertos, productores de energía, entre otros. Los enfoques analíticos tocan también temas nodales en el estudio de la acción colectiva como la ética, el despojo, los derechos humanos y las estrategias de comunicación y visibilización. Este material, que reúne estudios hechos en distintos lugares de México y Latinoamérica, es un compendio de métodos de investigación y un acercamiento al estudio de los movimientos sociales.UAEMEX, CONACyT, SE