Changes in chlorophyll fluorescence parameters during desiccation and osmotic stress of Hassallia antarctica culture

Hassallia antarctica is a terrestrial cyanobacterium colonizing various habitats in Antarctica such as soil surface, microbiological mats and seepages. H. antarctica represents one of the cyanobacterial species forming biodiversity of terrestrial autotrophs of James Ross Island, Antarctica. It is a filamentous cyanobacterium composing blackish fasciculated clusters thanks to false branching. In our study, sensitivity of the species to dehydration and salt stress was studied. We used H. antarctica culture (CCALA 956) grown on Z liquid medium. Clusters of H. antarctica were placed on wet filter paper and dried naturally at 5°C. During gradual dehydration, relative water content (RWC) was evaluated gravimetrically simultaneously with chlorophyll fluorescence measurements. Slow Kautsky kinetics and the chlorophyll fluorescence parameters (FV/FM, ФPSII) were used to assess dehydration-related decrease in primary photosynthetic processes. It was found that H. antarctica, contrastingly to other terrestrial cyanobacteria from polar habitats, was not able to maintain photosynthetic processes at RWCs as low as 20%. Even during initial phase of dehydration (RWC of 95%) rapid decline in FV/FM occured. Resistance of H. antarctica to osmotic stress was studied by time courses of the chlorophyll fluorescence parameter in response to 3.0, 0.3, and 0.03 M NaCl solution. Both shape of slow Kautsky kinetics and numeric values of chlorophyll fluorescence parameters were affected by osmotic stress. While full inhibitory effect was apparent in 3.0 M NaCl treatment immediately, the salt stress-induced decline in chlorophyll fluorescence parameters was observed at 0.03 M NaCl even after 8 hours of exposition. It was, therefore, concluded that H. antarctica exhibited high resistance to osmotic stress which may help the species to cope with repetitive dehydration events that happen in the field during austral summer season in Antarctica, James Ross Island in particular

Mindfulness y Cáncer: Aplicación del programa MBPM de Respira Vida Breatworks en pacientes oncológicos

El cáncer es una enfermedad frecuente y compleja que compromete la supervivencia de la persona que la padece, y genera un estrés socioemocional quecondiciona la calidad de vida y justifica la demanda de atención psicoterapéutica.Estudios previos muestran que un programa basado en mindfulness contribuye a un mayor ajuste psicológico en los pacientes oncológicos, reducción de los niveles de ansiedad y de depresión, mejoría de la calidad del sueño, uso de mejores estrategias de afrontamiento, cambios en el sistema inmune y endocrino, aumento de la calidad de vida y reducción del dolor. El objetivo del presente estudio es valorar la mejora del ajuste psicológico del paciente oncológico a través de la aplicación del programa de tratamiento MBPM.La muestra de pacientes (N=22) fue derivada de la unidad de psicooncología de la Asociación Española Contra el Cáncer de Valencia. Todos los sujetos fueron entrevistados y evaluados antes de la intervención y después de la misma, mediante una batería de cuestionarios.El programa MBPM creado por Vidyamala Burch. Se trata de una terapia grupal consta de 8 sesiones de 2,5 horas de duración y frecuencia semanal, que enseña una forma más sana de relacionarse con el sufrimiento, mediante la autogestión.Tras la intervención se observa una mejoría significativa en la escala que mide capacidad mindful, en la de autocompasión y en el bienestar psicológico, satisfacción con la vida y vitalidad subjetiva y una reducción significativa del dolor (p<0.05).Tal y como muestran los resultados, mejora el ajuste psicológico de los pacientes. Cabe destacar la importancia de replicar este estudio con un grupo control y un N mayor para poder generalizar estos resultados, aunque los resultados son prometedores.Cancer is a frequent and complex disease that compromises the survival of the person who suffers it, and generates a social-emotional stress that conditions the quality of life and justifies the demand for psychotherapeutic care.Previous studies show that a program based on mindfulness contributes to a greater psychological adjustment in oncological patients, reduction in levels of anxiety and depression, improvement of sleep quality, use of better coping strategies, changes in the immune system and endocrine, increased quality of life and pain reduction. The aim of the present study is to assess the improvement of the psychological adjustment of the oncological patient through the application of the MBPM treatment program.The sample of patients (N = 22) was derived from the psycho-oncology unit of the AECC Valencia. All the subjects were interviewed and evaluated before and after the intervention, through a battery of questionnaires.The MBPM program created by Vidyamala Burch. It is a group therapy consists of 8 sessions of 2.5 hours and weekly frequency, which teaches a healthier way of relating to suffering, through self-management.After the intervention a significant improvement was observed in the scale that measures mindful ability, in the self-compassion and in the well-being psychological, satisfaction with life and subjective vitality and a reduction of pain (p <0.05).As the results show, it improves the psychological adjustment of the patients. It is important to highlight the importance of replicating this study with a control group and a higher N in order to generalize these results, although the results are promising

In the moonlight: non-catalytic functions of ubiquitin and ubiquitin-like proteases

Proteases that cleave ubiquitin or ubiquitin-like proteins (UBLs) are critical players in maintaining the homeostasis of the organism. Concordantly, their dysregulation has been directly linked to various diseases, including cancer, neurodegeneration, developmental aberrations, cardiac disorders and inflammation. Given their potential as novel therapeutic targets, it is essential to fully understand their mechanisms of action. Traditionally, observed effects resulting from deficiencies in deubiquitinases (DUBs) and UBL proteases have often been attributed to the misregulation of substrate modification by ubiquitin or UBLs. Therefore, much research has focused on understanding the catalytic activities of these proteins. However, this view has overlooked the possibility that DUBs and UBL proteases might also have significant non-catalytic functions, which are more prevalent than previously believed and urgently require further investigation. Moreover, multiple examples have shown that either selective loss of only the protease activity or complete absence of these proteins can have different functional and physiological consequences. Furthermore, DUBs and UBL proteases have been shown to often contain domains or binding motifs that not only modulate their catalytic activity but can also mediate entirely different functions. This review aims to shed light on the non-catalytic, moonlighting functions of DUBs and UBL proteases, which extend beyond the hydrolysis of ubiquitin and UBL chains and are just beginning to emerge

Mindfulness and grief: The MADED program mindfulness for the acceptance of pain and emotions in grief

Objetivo: diseñar un protocolo de intervención psicológica para el acompañamiento del dolor y las emociones en el proceso de duelo basado en la atención y la compasión. Método: se incluirán dolientes mayores de 18 años, que hayan perdido al familiar al menos hace 6 meses, que se encuentren en la fase 2 o 3 de elaboración del duelo y sin presencia de problemas de salud mental previa. Se les evaluará después de firmar el consentimiento informado, mediante: el Cuestionario de Mindfulness, el Cuestionario de Satisfacción con la Vida, el Cuestionario de Vitalidad, la Escala Hospitalaria de Ansiedad y Depresión, la Escala de Afecto Positivo y Negativo e Inventario de Duelo Complicado. Se llevarán a cabo: estadísticos descriptivos, pruebas t para muestras independientes y d de Cohen o prueba U de Mann-Whitney r de Rosenthal si no se cumplen los supuestos. Además, se llevará a cabo un ANCOVA junto a eta cuadrado parcial. Resultado: el programa MADED (Mindfulness para la aceptación del dolor y las emociones en el duelo), consta de nueve sesiones semanales. Conclusión: Las sesiones que componen el programa facilitan la elaboración saludable del proceso de duelo basándose en la integración de los principios del mindfulness

Factors associated with discontinuation of biologics in patients with inflammatory arthritis in remission: data from the BIOBADASER registry

Background: The objectives of this study were to assess the discontinuation of biologic therapy in patients who achieve remission and identify predictors of discontinuation of biologics in patients with inflammatory arthritis in remission. Methods: An observational retrospective study from the BIOBADASER registry comprising adult patients diagnosed with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA) and receiving 1 or 2 biological disease-modifying drugs (bDMARDs) between October 1999 and April 2021. Patients were followed yearly after initiation of therapy or until discontinuation of treatment. Reasons for discontinuation were collected. Patients who discontinued bDMARDs because of remission as defined by the attending clinician were studied. Predictors of discontinuation were explored using multivariable regression models. Results: The study population comprised 3,366 patients taking 1 or 2 bDMARDs. Biologics were discontinued owing to remission by 80 patients (2.4%): 30 with RA (1.7%), 18 with AS (2.4%), and 32 with PsA (3.9%). The factors associated with a higher probability of discontinuation on remission were shorter disease duration (OR: 0.95; 95% CI: 0.91-0.99), no concomitant use of classic DMARDs (OR: 0.56; 95% CI: 0.34-0.92), and shorter usage of the previous bDMARD (before the decision to discontinue biological therapy) (OR: 1.01; 95% CI: 1.01-1.02); in contrast, smoking status (OR: 2.48; 95% CI: 1.21-5.08) was associated with a lower probability. In patients with RA, positive ACPA was associated with a lower probability of discontinuation (OR: 0.11; 95% CI: 0.02-0.53). Conclusions: Discontinuation of bDMARDs in patients who achieve remission is uncommon in routine clinical care. Smoking and positive ACPA in RA patients were associated with a lower probability of treatment discontinuation because of clinical remission.This research is supported by the Research Unit of the Spanish Society of Rheumatology. BIOBADASER is supported by the Spanish Agency of Medicines and Medical Devices (AEMPS), Biogen, Bristol-Myers and Squibb (BMS), Celltrion, Janssen, Lilly, Merck Sharp and Dohme (MSD), Novartis, Pfizer, Regeneron, and Samsung Bioepis.S

Novel Machado-Joseph disease-modifying genes and pathways identified by whole-exome sequencing

Funding Information: This work was funded by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020 , and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia / Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project PTDC/DTP-PIC/2638/2017 ( POCI-01-0145-FEDER-016592 ); GenomePT ( POCI-01-0145-FEDER-022184 ); ICVS Scientific Microscopy Platform , member of the national infrastructure PPBI - Portuguese Platform of Bioimaging ( PPBI-POCI-01-0145-FEDER-022122 ; by National funds , through the Foundation for Science and Technology (FCT) - project UIDB/50026/2020 and UIDP/50026/2020 ; and by the project NORTE-01-0145-FEDER-000013 , supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) . MR is supported by FCT ( CEECIND/03018/2018 ). ARVM ( SFRH/BD/129547/2017 ) and AFF ( SFRH/BD/121101/2016 ) are supported by a PhD grant financed by FCT . CB is supported by the Multiple System Atrophy Trust and Alzheimer's Research UK . MDC received funding from National Ataxia Foundation (NAF) and from FCT ( SFRH/BPD/101925/2014 ); DV-C received a grant from FCT ( SFRH/BD/147826/2019 ). Publisher Copyright: © 2021Machado-Joseph disease (MJD/SCA3) is a neurodegenerative polyglutamine disorder exhibiting a wide spectrum of phenotypes. The abnormal size of the (CAG)n at ATXN3 explains ~55% of the age at onset variance, suggesting the involvement of other factors, namely genetic modifiers, whose identification remains limited. Our aim was to find novel genetic modifiers, analyse their epistatic effects and identify disease-modifying pathways contributing to MJD variable expressivity. We performed whole-exome sequencing in a discovery sample of four age at onset concordant and four discordant first-degree relative pairs of Azorean patients, to identify candidate variants which genotypes differed for each discordant pair but were shared in each concordant pair. Variants identified by this approach were then tested in an independent multi-origin cohort of 282 MJD patients. Whole-exome sequencing identified 233 candidate variants, from which 82 variants in 53 genes were prioritized for downstream analysis. Eighteen disease-modifying pathways were identified; two of the most enriched pathways were relevant for the nervous system, namely the neuregulin signaling and the agrin interactions at neuromuscular junction. Variants at PARD3, NFKB1, CHD5, ACTG1, CFAP57, DLGAP2, ITGB1, DIDO1 and CERS4 modulate age at onset in MJD, with those identified in CFAP57, ACTG1 and DIDO1 showing consistent effects across cohorts of different geographical origins. Network analyses of the nine novel MJD modifiers highlighted several important molecular interactions, including genes/proteins previously related with MJD pathogenesis, namely between ACTG1/APOE and VCP/ITGB1. We describe novel pathways, modifiers, and their interaction partners, providing a broad molecular portrait of age at onset modulation to be further exploited as new disease-modifying targets for MJD and related diseases.publishersversionpublishe

Primary constitutional MLH1 epimutations: a focal epigenetic event

BACKGROUND: Constitutional MLH1 epimutations are characterised by monoallelic methylation of the MLH1 promoter throughout normal tissues, accompanied by allele-specific silencing. The mechanism underlying primary MLH1 epimutations is currently unknown. The aim of this study was to perform an in-depth characterisation of constitutional MLH1 epimutations targeting the aberrantly methylated region around MLH1 and other genomic loci. METHODS: Twelve MLH1 epimutation carriers, 61 Lynch syndrome patients, and 41 healthy controls, were analysed by Infinium 450 K array. Targeted molecular techniques were used to characterise the MLH1 epimutation carriers and their inheritance pattern. RESULTS: No nucleotide or structural variants were identified in-cis on the epimutated allele in 10 carriers, in which inter- generational methylation erasure was demonstrated in two, suggesting primary type of epimutation. CNVs outside the MLH1 locus were found in two cases. EPM2AIP1-MLH1 CpG island was identified as the sole differentially methylated region in MLH1 epimutation carriers compared to controls. CONCLUSION: Primary constitutional MLH1 epimutations arise as a focal epigenetic event at the EPM2AIP1-MLH1 CpG island in the absence of cis-acting genetic variants. Further molecular characterisation is needed to elucidate the mechanistic basis of MLH1 epimutations and their heritability/reversibility

Novel Machado-Joseph disease-modifying genes and pathways identified by whole-exome sequencing

Machado-Joseph disease (MJD/SCA3) is a neurodegenerative polyglutamine disorder exhibiting a wide spectrum of phenotypes. The abnormal size of the (CAG)n at ATXN3 explains ~55% of the age at onset variance, suggesting the involvement of other factors, namely genetic modifiers, whose identification remains limited. Our aim was to find novel genetic modifiers, analyse their epistatic effects and identify disease-modifying pathways contributing to MJD variable expressivity. We performed whole-exome sequencing in a discovery sample of four age at onset concordant and four discordant first-degree relative pairs of Azorean patients, to identify candidate variants which genotypes differed for each discordant pair but were shared in each concordant pair. Variants identified by this approach were then tested in an independent multi-origin cohort of 282 MJD patients. Whole-exome sequencing identified 233 candidate variants, from which 82 variants in 53 genes were prioritized for downstream analysis. Eighteen disease-modifying pathways were identified; two of the most enriched pathways were relevant for the nervous system, namely the neuregulin signaling and the agrin interactions at neuromuscular junction. Variants at PARD3, NFKB1, CHD5, ACTG1, CFAP57, DLGAP2, ITGB1, DIDO1 and CERS4 modulate age at onset in MJD, with those identified in CFAP57, ACTG1 and DIDO1 showing consistent effects across cohorts of different geographical origins. Network analyses of the nine novel MJD modifiers highlighted several important molecular interactions, including genes/proteins previously related with MJD pathogenesis, namely between ACTG1/APOE and VCP/ITGB1. We describe novel pathways, modifiers, and their interaction partners, providing a broad molecular portrait of age at onset modulation to be further exploited as new disease-modifying targets for MJD and related diseases

Mammalian Glutaminase Gls2 Gene Encodes Two Functional Alternative Transcripts by a Surrogate Promoter Usage Mechanism

Glutaminase is expressed in most mammalian tissues and cancer cells, but the regulation of its expression is poorly understood. An essential step to accomplish this goal is the characterization of its species- and cell-specific isoenzyme pattern of expression. Our aim was to identify and characterize transcript variants of the mammalian glutaminase Gls2 gene.We demonstrate for the first time simultaneous expression of two transcript variants from the Gls2 gene in human, rat and mouse. A combination of RT-PCR, primer-extension analysis, bioinformatics, real-time PCR, in vitro transcription and translation and immunoblot analysis was applied to investigate GLS2 transcripts in mammalian tissues. Short (LGA) and long (GAB) transcript forms were isolated in brain and liver tissue of human, rat and mouse. The short LGA transcript arises by a combination of two mechanisms of transcriptional modulation: alternative transcription initiation and alternative promoter. The LGA variant contains both the transcription start site (TSS) and the alternative promoter in the first intron of the Gls2 gene. The full human LGA transcript has two in-frame ATGs in the first exon, which are missing in orthologous rat and mouse transcripts. In vitro transcription and translation of human LGA yielded two polypeptides of the predicted size, but only the canonical full-length protein displayed catalytic activity. Relative abundance of GAB and LGA transcripts showed marked variations depending on species and tissues analyzed.This is the first report demonstrating expression of alternative transcripts of the mammalian Gls2 gene. Transcriptional mechanisms giving rise to GLS2 variants and isolation of novel GLS2 transcripts in human, rat and mouse are presented. Results were also confirmed at the protein level, where catalytic activity was demonstrated for the human LGA protein. Relative abundance of GAB and LGA transcripts was species- and tissue-specific providing evidence of a differential regulation of GLS2 transcripts in mammals

PERSPECTIVA PSICOSOCIAL DE LOS DERECHOS HUMANOS

Hoy en día es imprescindible abordar el problema de los derechos desde una perspectiva holística que integre la posición que el individuo ocupa en la sociedad y el impacto de los hechos sociales sobre su persona. Esta perspectiva va por lo tanto más allá del enfoque clásico de las violaciones a los derechos civiles y políticos de los ciudadanos sino, también incluye sus derechos económicos, sociales y culturales. Cualquier enfoque de tipo holístico debe entender al ser humano en su ambiente, social, cultural, natural y en función a todas las estructuras existentes, por más sutiles que sean o invisibles que parezcan. Precisamente este libro permite apreciar la dimensión amplia y compleja del ser en sociedad y las interacciones que de ambas partes se generan y las ramificaciones que producen. No es un ejercicio fácil y los editores de este volumen han logrado un salto cuántico al poder congregar en un solo espacio miradas que en otras circunstancias podrían haber sido opuestas y hasta contrarias a nuestra comprensión de problemas que, en efecto, tienen raíces comunes. El libro está dividido en 5 secciones, El espíritu de los tiempos actuales y los Derechos Humanos, Construcción ciudadana y ejercicio de los Derechos Humanos, Violaciones a Derechos Humanos, victimizaciones y su atención, Ejercicio de los Derechos Humanos y situaciones disruptivas y Defensa y defensores de Derechos Humanos.Manuel Gutiérrez Romero Jessica Ruiz Magañ