Phosphorylation regulates human polη stability and damage bypass throughout the cell cycle

DNA translesion synthesis (TLS) is a crucial damage tolerance pathway that oversees the completion of DNA replication in the presence of DNA damage. TLS polymerases are capable of bypassing a distorted template but they are generally considered inaccurate and they need to be tightly regulated. We have previously shown that polη is phosphorylated on Serine 601 after DNA damage and we have demonstrated that this modification is important for efficient damage bypass. Here we report that polη is also phosphorylated by CDK2, in the absence of damage, in a cell cycle-dependent manner and we identify serine 687 as an important residue targeted by the kinase. We discover that phosphorylation on serine 687 regulates the stability of the polymerase during the cell cycle, allowing it to accumulate in late S and G2 when productive TLS is critical for cell survival. Furthermore, we show that alongside the phosphorylation of S601, the phosphorylation of S687 and S510, S512 and/or S514 are important for damage bypass and cell survival after UV irradiation. Taken together our results provide new insights into how cells can, at different times, modulate DNA TLS for improved cell survival

"I am feeling tension in my whole body": An experimental phenomenological study of empathy for pain

Introduction: Traditionally, empathy has been studied from two main perspectives: the theory-theory approach and the simulation theory approach. These theories claim that social emotions are fundamentally constituted by mind states in the brain. In contrast, classical phenomenology and recent research based on enactive theories consider empathy as the basic process of contacting others’ emotional experiences through direct bodily perception and sensation. Objective: This study aims to enrich knowledge of the empathic experience of pain by using an experimental phenomenological method. Method: Implementing an experimental paradigm used in affective neuroscience, we exposed 28 healthy adults to a video of sportspersons suffering physical accidents while practicing extreme sports. Immediately after watching the video, each participant underwent a phenomenological interview to gather data on embodied, multi-layered dimensions (bodily sensations, emotions, and motivations) and temporal aspects of empathic experience. We also performed quantitative analyses of the phenomenological categories. Results: Experiential access to the other person’s painful experience involves four main-themes. Bodily resonance: participants felt a multiplicity of bodily, affective, and kinesthetic sensations. Attentional focus: some participants centered their attention more on their own personal discomfort and sensations of rejection, while others on the pain and suffering experienced by the sportspersons. Kinesthetic motivation: some participants experienced the feeling in their bodies to avoid or escape from watching the video, while others experienced the need to help the sportspersons avoid suffering any injury while practicing extreme sports. Temporality of experience: participants witnessed temporal fluctuations in their experiences, bringing intensity changes in their bodily resonance, attentional focus, and kinesthetic motivation. Finally, two experiential structures were found: one structure is self-centered empathic experience, characterized by bodily resonance, attentional focus centered on the participant’s own experience of seeing the sportsperson suffering, and self-protective kinesthetic motivation; the other structure is other-centered empathic experience, characterized by bodily resonance, attentional focus centered on the sportsperson, and prosocial kinesthetic motivation to help them. Discussion: We show how phenomenological data may contribute to comprehending empathy for pain in social neuroscience. In addition, we address the phenomenological aspect of the enactive approach to the three dimensions of embodiment of human consciousness, especially the intersubjective dimension. Also, based on our results, we suggest an extension of the enactive theory for non-interactive social experience

Effects of countdown displays in public transport route choice under severe overcrowding

The paper presents a route choice model for dynamic assignment in congested, i.e. overcrowded, transit networks where it is assumed that passengers are supported with real-time information on carrier arrivals at stops. If the stop layout is such that passenger congestion results in First-In-First-Out (FIFO) queues, a new formulation is devised for calculating waiting times, total travel times and route splits. Numerical results for a simple example network show the effect of information on route choice when heavy congestion is observed. While the provision of information does not lead to a remarkable decrease in total travel time, with the exception of some particular instances, it changes the travel behaviour of passengers that seem to be more averse to queuing at later stages of their journey and, thus, prefer to interchange at less congested stations

Anti-Angiogenic Therapy Induces Integrin-Linked Kinase 1 Up-Regulation in a Mouse Model of Glioblastoma

BACKGROUND: In order to improve our understanding of the molecular pathways that mediate tumor proliferation and angiogenesis, and to evaluate the biological response to anti-angiogenic therapy, we analyzed the changes in the protein profile of glioblastoma in response to treatment with recombinant human Platelet Factor 4-DLR mutated protein (PF4-DLR), an inhibitor of angiogenesis. METHODOLOGY/PRINCIPAL FINDINGS: U87-derived experimental glioblastomas were grown in the brain of xenografted nude mice, treated with PF4-DLR, and processed for proteomic analysis. More than fifty proteins were differentially expressed in response to PF4-DLR treatment. Among them, integrin-linked kinase 1 (ILK1) signaling pathway was first down-regulated but then up-regulated after treatment for prolonged period. The activity of PF4-DLR can be increased by simultaneously treating mice orthotopically implanted with glioblastomas, with ILK1-specific siRNA. As ILK1 is related to malignant progression and a poor prognosis in various types of tumors, we measured ILK1 expression in human glioblastomas, astrocytomas and oligodendrogliomas, and found that it varied widely; however, a high level of ILK1 expression was correlated to a poor prognosis. CONCLUSIONS/SIGNIFICANCE: Our results suggest that identifying the molecular pathways induced by anti-angiogenic therapies may help the development of combinatorial treatment strategies that increase the therapeutic efficacy of angiogenesis inhibitors by association with specific agents that disrupt signaling in tumor cells

Envejecimiento de la población

•Actividades básicas de la vida diaria en personas mayores y factores asociados •Asociación entre depresión y posesión de mascotas en personas mayores •Calidad de vida en adultos mayores de Santiago aplicando el instrumento WHOQOL-BREF •Calidad de vida en usuarios con enfermedad de Parkinson, demencia y sus cuidadores, comuna de Vitacura •Caracterización de egresos hospitalarios de adultos mayores en Puerto Natales (2007-2009) •Comportamiento de las patologías incluidas como GES para el adulto mayor atendido en un Cesfam •Contribución de vitaminas y minerales a las ingestas recomendadas diarias en ancianos institucionalizados de Madrid •Estado de salud oral del paciente inscrito en el Programa de Visita Domiciliaria •Evaluación del programa de discapacidad severa en Casablanca con la matriz de marco lógico •Factores asociados a satisfacción vital en una cohorte de adultos mayores de Santiago, Chile •Pauta instrumental para la identificación de riesgos para el adulto mayor autovalente, en su vivienda •Perfil farmacológico del paciente geriátrico institucionalizado y posibles consecuencias en el deterioro cognitivo •Programa de cuidados paliativos y alivio del dolor en Puerto Natales •Rehabilitación mandibular implantoprotésica: efecto en calidad de vida relacionada con salud bucal en adultos mayores •Salud bucodental en adultos mayores autovalentes de la Región de Valparaíso •Transición epidemiológica y el estudio de carga de enfermedad en Brasi

Impacts of sex differences on optogenetic, chemogenetic, and calcium-imaging tools

Technical innovation in neuroscience introduced powerful tools for measuring and manipulating neuronal activity via optical, chemogenetic, and calcium-imaging tools. These tools were initially tested primarily in male animals but are now increasingly being used in females as well. In this review, we consider how these tools may work differently in males and females. For example, we review sex differences in the metabolism of chemogenetic ligands and their downstream signaling effects. Optical tools more directly alter depolarization or hyperpolarization of neurons, but biological sex and gonadal hormones modulate synaptic inputs and intrinsic excitability. We review studies demonstrating that optogenetic manipulations are sometimes consistent across the rodent estrous cycle but within certain circuits; manipulations can vary across the ovarian cycle. Finally, calcium-imaging methods utilize genetically encoded calcium indicators to measure neuronal activity. Testosterone and estradiol can directly modulate calcium influx, and we consider these implications for interpreting the results of calcium-imaging studies. Together, our findings suggest that these neuroscientific tools may sometimes work differently in males and females and that users should be aware of these differences when applying these methods

Envejecimiento de la población

•Actividades básicas de la vida diaria en personas mayores y factores asociados •Asociación entre depresión y posesión de mascotas en personas mayores •Calidad de vida en adultos mayores de Santiago aplicando el instrumento WHOQOL-BREF •Calidad de vida en usuarios con enfermedad de Parkinson, demencia y sus cuidadores, comuna de Vitacura •Caracterización de egresos hospitalarios de adultos mayores en Puerto Natales (2007-2009) •Comportamiento de las patologías incluidas como GES para el adulto mayor atendido en un Cesfam •Contribución de vitaminas y minerales a las ingestas recomendadas diarias en ancianos institucionalizados de Madrid •Estado de salud oral del paciente inscrito en el Programa de Visita Domiciliaria •Evaluación del programa de discapacidad severa en Casablanca con la matriz de marco lógico •Factores asociados a satisfacción vital en una cohorte de adultos mayores de Santiago, Chile •Pauta instrumental para la identificación de riesgos para el adulto mayor autovalente, en su vivienda •Perfil farmacológico del paciente geriátrico institucionalizado y posibles consecuencias en el deterioro cognitivo •Programa de cuidados paliativos y alivio del dolor en Puerto Natales •Rehabilitación mandibular implantoprotésica: efecto en calidad de vida relacionada con salud bucal en adultos mayores •Salud bucodental en adultos mayores autovalentes de la Región de Valparaíso •Transición epidemiológica y el estudio de carga de enfermedad en Brasi