Orderly progression through S-phase requires dynamic ubiquitylation and deubiquitylation of PCNA

[EN] Proliferating-cell nuclear antigen (PCNA) is a DNA sliding clamp with an essential function in DNA replication and a key role in tolerance to DNA damage by ensuring the bypass of lesions. In eukaryotes, DNA damage tolerance is regulated by ubiquitylation of lysine 164 of PCNA through a well-known control mechanism; however, the regulation of PCNA deubiquitylation remains poorly understood. Our work is a systematic and functional study on PCNA deubiquitylating enzymes (DUBs) in Schizosaccharomyces pombe. Our study reveals that the deubiquitylation of PCNA in fission yeast cells is a complex process that requires several ubiquitin proteases dedicated to the deubiquitylation of a specific subnuclear fraction of mono- and di-ubiquitylated PCNA or a particular type of poly-ubiquitylated PCNA and that there is little redundancy among these enzymes. To understand how DUB activity regulates the oscillatory pattern of ubiquitylated PCNA in fission yeast, we assembled multiple DUB mutants and found that a quadruple mutation of ubp2+, ubp12+, ubp15+ and ubp16+ leads to the stable accumulation of mono-, di- and poly-ubiquitylated forms of PCNA, increases S-phase duration and sensitizes cells to DNA damage. Our data suggest that the dynamic ubiquitylation and deubiquitylation of PCNA occurs during S-phase to ensure processive DNA replication

Las bibliotecas como espacio de trabajo y contención: análisis de factores riesgo

El presente trabajo adopta el enfoque de la gestión del riesgo (GRi) para abordar el espacio de trabajo de profesionales de la información y de contención del alumnado en las bibliotecas pertenecientes a la Universidad Nacional de La Plata (Argentina). Se toma como punto de partida una revisión bibliográfica proveniente de distintos ámbitos. Asimismo, se realiza un estudio de tipo exploratorio a través de la observación y las entrevistas informales con referentes para el análisis del espacio de las bibliotecas. Se describen los riesgos a los que están expuestos quienes trabajan y las transitan, que son de índole naturales o físicos; tecnológicos; de seguridad; psicológicos; químicos. Se esbozan algunas conclusiones preliminares y se plantean las líneas de indagación a seguir en el futuro cercano.Facultad de Humanidades y Ciencias de la Educació

Un abordaje de la desinformación: recursos digitales en el aula

En estos tiempos, la información corre rápidamente por los distintos medios de comunicación. Estamos acostumbrados a leer y difundir inmediatamente la información y los hechos que suceden. Sin embargo, una de las cuestiones consiste en saber si los sucesos son correctos o incorrectos y reconocer si la sobreabundancia informativa puede convertirse en un gran inconveniente. Por este motivo, el presente texto expone una experiencia realizada en el seminario denominado “La búsqueda en bibliotecología: una aproximación a la infodemia, las falsas noticias y la estrategia de la verdad” en la Facultad de Humanidades y Ciencias de la Educación de la Universidad Nacional de La Plata, durante la cursada de verano de este año a los/as alumnos/as de la carrera de licenciatura en Bibliotecología y Ciencia de la Información. En dicho curso, se detallaron diversos recursos digitales y trabajamos en conjunto para pensar y reflexionar sobre la verificación de la información y las noticias.Especialización en Docencia UniversitariaInstituto de Investigaciones en Humanidades y Ciencias Sociale

Effects of anosognosia and neuropsychiatric symptoms on the quality of life of patients with alzheimer's disease: a 24-month follow-up study

Objectives: Neuropsychiatric symptoms and anosognosia are known to influence the perceived quality of life of patients (QoL-p) with Alzheimer's disease (AD). This study analysed their impact on patient and caregiver ratings of QoL-p and how these ratings changed in relation to the severity of dementia. Methods: A baseline sample of 221 patients and caregivers was followed up over 24 months. Instruments: Neuropsychiatric Inventory (NPI), Anosognosia Questionnaire-Dementia (AQ-D), Quality of Life-Alzheimer's Disease (QoL-AD), and the Global Deterioration Scale (GDS). Longitudinal data were analysed using generalized linear models. Results: In the multivariate analysis, greater anosognosia was always associated with higher ratings of QoL-p among patients, especially at 24 months (p < 0.001), and with more negative ratings among caregivers, especially at baseline (p < 0.001). A higher total NPI score was associated with a more negative rating of QoL-p among caregivers (p < 0.001), and it also had a smaller negative effect on patients' self-ratings (p = 0.001). The neuropsychiatric symptoms (NPI) associated with a more negative view of QoL-p were depression, for patients' self-ratings, and apathy and agitation for caregiver ratings. The discrepancy between patient and caregiver ratings increased in line with the severity of dementia. Conclusion: Neuropsychiatric symptoms and anosognosia have differential effects on patient and caregiver ratings of the quality of life of patients with Alzheimer's disease. Key words: Alzheimer's disease, quality of life, anosognosia, neuropsychiatric symptoms, caregivers, patients

Kinship and cohabitation in relation to caregiver burden in the context of Alzheimer's disease: a 24-month longitudinal study

Objectives: The aims of the study were to identify the clinical characteristics of three groups of caregivers: spouses, live-in adult-child or non-live-in adult-child, and their relation to the degree of perceived burden (Caregiver Burden Interview). Methods: The sample comprised 275 Alzheimer's disease (AD) primary caregivers, with a follow-up of 24 months. Cognitive, functional and behavioural characteristics were evaluated in persons with AD (PwD), while socio-demographic data, use of socio-medical resources, physical and mental health, and self-perceived burden were assessed in caregivers. Generalized estimating equations (GEE) were used for longitudinal data analysis. Results: Spouse caregivers were 45.0% men, sole caregivers (> 80%), used few external resources, and had worse physical health. The number of female adult-child caregivers was higher (>75%). The live-in adult-child group, compared with the non-live-in adult-child group, were less likely to be married, had a lower level of education, were more commonly the sole caregiver, and used fewer external resources. The greatest burden was observed in live-in adult-child caregivers, and the lowest in the non-live-in adult-child group, with no significant variation in the follow-up for both groups. Spouses had an intermediate level of perceived burden, which rose significantly during follow-up (p <0.001). Conclusions: Kinship and cohabitation with the PwD were associated with different scores and evolution of the burden, with an increase in the follow-up of the spouses, and with more or less burden, depending on cohabitation, in the adult-child groups. Interventions to reduce the level of burden on caregivers should consider these differences

Síntomas depresivos y sobrecarga en los familiares cuidadores en la enfermedad de Alzheimer: un modelo de ecuaciones estructurales

Introducción. El cuidado de los pacientes con Enfermedad de Alzheimer (EA) incrementa la sobrecarga y depresión del cuidador principal (CP), aunque la relación entre ambas no está claramente definida. Objetivo. Explorar los factores asociados a la sintomatología depresiva y sobrecarga en el CP y aplicar un modelo de ecuaciones estructurales para identificar la relación entre ellas. Sujetos y métodos. La muestra estuvo formada por 127 cuidadores familiares de personas con EA, con un seguimiento de 24 meses. Se realizaron análisis de regresión multivariante para identificar las características de pacientes y cuidadores asociadas a la sobrecarga y depresión del CP, y se diseñó un modelo de ecuaciones estructurales para analizar la relación entre las variables. Resultados. En el modelo de ecuaciones estructurales, la sobrecarga tuvo un efecto directo sobre la depresión, tanto en la evaluación basal como a los 24 meses. Las variables asociadas a la sobrecarga fueron: la escolaridad y la menor salud mental del CP; y las alteraciones conductuales y la dependencia funcional del paciente. El menor nivel cognitivo del paciente y la menor salud mental del CP estuvieron asociadas a la depresión. La correlación entre sobrecarga y depresión aumentó desde la evaluación basal hasta los 2 años (r = 0,470 vs. 0,613). Conclusiones. El deterioro del paciente y la sobrecarga son factores de riesgo para la depresión en el CP. Serían necesarias intervenciones para reducir la carga y poder prevenir la depresión relacionada

Factors associated with the variability in caregiver assessments of the capacities of the patients with Alzheimer"s disease

Abstract Background: Several studies have identified certain caregiver factors that can produce variability in their assessments of the capacities of patients with Alzheimer"s disease (AD). Objectives: To identify the caregiver variables associated with variability in their ratings of patients" capacities. Methods: Consecutive sample of 221 out-patients with AD and their family caregivers. The capacities evaluated by caregivers were: the degree of functional disability, using the Disability Assessment for Dementia (DAD); psychological and behavioral symptoms, via the Neuropsychiatric Inventory (NPI); anosognosia, with the Anosognosia Questionnaire Dementia (AQ-D); and quality of life, using the Quality of Life in AD (QOL-AD). The relationship between these measures and caregiver gender, burden, depression, and health was analyzed by means of a bivariate analysis, calculating the effect size (Cohen"s d), and subsequently by a regression analysis, calculating the contribution coefficient (CC). Results: The greatest variability in caregiver assessments was observed in relation to patients with early-stage dementia, where caregiver burden was the main factor associated with a more negative evaluation (d = 1.02 to 1.25). Depression in the caregiver was associated with less variability and only in the assessments of patients with moderate dementia (d = 0.38 to 0.69). In the regression analysis, caregiver factors were associated with greater variance in scores on the NPI (CC = 37.4%) and QOL-AD (CC = 27.2%), and lower variance in AQ-D (CC = 21.6%) and DAD (CC = 10.3%) scores. Conclusions: Caregiver burden and depression were associated with more negative assessments of patients" psychological and behavioral symptoms and quality of life. Key words: Alzheimer"s disease, family caregivers, functional capacity, neuropsychiatric symptoms, anosognosia, quality of life

Caregivers' sense of coherence: Implications on direct and indirect costs of dementia care

Background: Dementia care is associated with physical, emotional, and monetary impact on the informal carers providing unpaid care. Differences in the personal characteristics of caregivers may help explain the variations in the costs of dementia care. Objective: The aim of this study was to analyze the effect of caregivers' sense of coherence (SOC) on direct and indirect costs in dementia care. Methods: A cross-sectional study was conducted in community dwelling caregivers of patients with Alzheimer's disease. Data of healthcare services were obtained from clinical registries, and information was collected from caregivers regarding their use of social care resources and time spent caregiving. The transformation of all costs into Euros was made assigning a fixed cost of 10.29€ /h and 16.24€ /h for assisting in instrumental and basic activities of daily living, respectively. Caregivers' SOC was assessed using the Orientation to Life Questionnaire (OLQ-13). Adjusted regression models were developed, with different types of costs as dependent variables. Results: A sample of 147 caregivers was recruited. The mean OLQ-13 score was 73.3 points (SD=11.6). The regression models showed a small association between caregivers' SOC and direct costs, mainly linked to the use of social care resources (r2=0.429; ß=-15.6€ /month), and a greater association between SOC and indirect costs (r2=0.562; ß=-222.3€ /month). Conclusion: Increasing caregivers' SOC could reduce dementia care costs by decreasing the use of social care resources and caregiving time

Self-perceived quality of life among patients with Alzheimer's disease: Two longitudinal models of analysis

The objective was to analyze the factors that influence self-perceived quality of life (QoL) in patients with Alzheimer's disease (AD), contrasting two different longitudinal models. A total of 127 patients were followed up over 24 months. The instruments applied were: Quality of Life in Alzheimer's Disease scale (QoL-AD), Geriatric Depression Scale-15, Anosognosia Questionnaire-Dementia, Disability Assessment in Dementia, Neuropsychiatric Inventory, and the Mini Mental State Examination. Two models for grouping patients were tested: 1) Baseline score on the QoL-AD (QoL-Baseline), and 2) Difference in QoL-AD score between baseline and follow-up (QoL-Change). Generalized estimating equations (GEE) were used to analyze longitudinal data, and multinomial regression analyses were performed. Over the follow-up period the QoL-Baseline model showed greater variability between groups (Wald χ2 = 172.3, p 37 QoL-AD). The model based on baseline scores (QoL-Baseline) was better than the QoL-Change model in terms of identifying trajectories and predictors of QoL in AD

Locus coeruleus connectivity alterations in late-life major depressive disorder during a visual oddball task

The Locus Coeruleus (LC) is the major source of noradrenergic neurotransmission. Structural alterations in the LC have been observed in neurodegenerative disorders and at-risk individuals, although functional connectivity studies between the LC and other brain areas have not been yet performed in these populations. Patients with late-life major depressive disorder (MDD) are indeed at increased risk for neurodegenerative disorders, and here we investigated LC connectivity in late-life MDD in comparison to individuals with amnestic type mild cognitive impairment (aMCI) and healthy controls (HCs). We assessed 20 patients with late-life MDD, 16 patients with aMCI, and 26 HCs, who underwent a functional magnetic resonance scan while performing a visual oddball task. We assessed task-related modulations of LC connectivity (i.e., Psychophysiological Interactions, PPI) with other brain areas. A T1-weighted fast spin-echo sequence for LC localization was also obtained. Patients with late-life MDD showed lower global connectivity during target detection in a cluster encompassing the right caudal LC. Specifically, we observed lower LC connectivity with the left anterior cingulate cortex (ACC), the right fusiform gyrus, and different cerebellar clusters. Moreover, alterations in LC-ACC connectivity correlated negatively with depression severity (i.e., Geriatric Depression Scale and number of recurrences). Reduced connectivity of the LC during oddball performance seems to specifically characterize patients with late-life MDD, but not other populations of aged individuals with cognitive alterations. Such alteration is associated with different measures of disease severity, such as the current presence of symptoms and the burden of disease (number of recurrences)