182 research outputs found

    Interaction between the Rev1 C-Terminal Domain and the PolD3 Subunit of Polζ Suggests a Mechanism of Polymerase Exchange upon Rev1/Polζ-Dependent Translesion Synthesis

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    Translesion synthesis (TLS) is a mutagenic branch of cellular DNA damage tolerance that enables bypass replication over DNA lesions carried out by specialized low-fidelity DNA polymerases. The replicative bypass of most types of DNA damage is performed in a two-step process of Rev1/Polζ-dependent TLS. In the first step, a Y-family TLS enzyme, typically Polη, Polι, or Polκ, inserts a nucleotide across a DNA lesion. In the second step, a four-subunit B-family DNA polymerase Polζ (Rev3/Rev7/PolD2/PolD3 complex) extends the distorted DNA primer-template. The coordinated action of error-prone TLS enzymes is regulated through their interactions with the two scaffold proteins, the sliding clamp PCNA and the TLS polymerase Rev1. Rev1 interactions with all other TLS enzymes are mediated by its C-terminal domain (Rev1-CT), which can simultaneously bind the Rev7 subunit of Polζ and Rev1-interacting regions (RIRs) from Polη, Polι, or Polκ. In this work, we identified a previously unknown RIR motif in the C-terminal part of PolD3 subunit of Polζ whose interaction with the Rev1-CT is among the tightest mediated by RIR motifs. Three-dimensional structure of the Rev1-CT/PolD3-RIR complex determined by NMR spectroscopy revealed a structural basis for the relatively high affinity of this interaction. The unexpected discovery of PolD3-RIR motif suggests a mechanism of “inserter” to “extender” DNA polymerase switch upon Rev1/Polζ-dependent TLS, in which the PolD3-RIR binding to the Rev1-CT (i) helps displace the “inserter” Polη, Polι, or Polκ from its complex with Rev1, and (ii) facilitates assembly of the four-subunit “extender” Polζ through simultaneous interaction of Rev1-CT with Rev7 and PolD3 subunits

    Structural brain preservation: a potential bridge to future medical technologies

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    When faced with the prospect of death, some people would prefer a form of long-term preservation that may allow them to be restored to healthy life in the future, if technology ever develops to the point that this is feasible and humane. Some believe that we may have the capacity to perform this type of experimental preservation today—although it has never been proven—using contemporary methods to preserve the structure of the brain. The idea is that the morphomolecular organization of the brain encodes the information required for psychological properties such as personality and long-term memories. If these structures in the brain can be maintained intact over time, this could theoretically provide a bridge to access restorative technologies in the future. To consider this hypothesis, we first describe possible metrics that can be used to assess structural brain preservation quality. We next explore several possible methods to preserve structural information in the brain, including the traditional cryonics method of cryopreservation, as well as aldehyde-stabilized cryopreservation and fluid preservation. We focus in-depth on fluid preservation, which relies on aldehyde fixation to induce chemical gel formation in a wide set of biomolecules and appears to be a cost-effective method. We describe two theoretical recovery technologies, alongside several of the ethical and legal complexities of brain preservation, all of which will require a prudent approach. We believe contemporary structural brain preservation methods have a non-negligible chance of allowing successful restoration in the future and that this deserves serious research efforts by the scientific community

    Using the Parent-Infant Relationship Global Assessment Scale (PIR-GAS) to identify caregiver – infant/toddler dyads with abusive relationship patterns in six European countries:Identify Abusive Relationships With the PIR-GAS

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    The study examined whether the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood, Revised Edition (DC: 0-3R; ZERO TO THREE, 2005) Parent-Infant Relationship Global Assessment Scale (PIR-GAS) is applicable to six European countries and contributes to the identification of caregiver-infant/toddler dyads with abusive relationship patterns. The sample consisted of 115 dyads with children's ages ranging from 1 to 47 months. Sixty-four dyads were recruited from community settings without known violence problems, and 51 dyads were recruited from clinical settings and already had been identified with violence problems or as being at risk for violence problems. To classify the dyads on the PIR-GAS categories, caregiver-child interactions were video-recorded and coded with observational scales appropriate for child age. To test whether the PIR-GAS allows for reliable identification of dyads with abusive relationship patterns, PIR-GAS ratings were compared with scores on the the International Society for the Prevention of Child Abuse and Neglect's (ISPCAN) Child Abuse Screening Tool-Parental Version (ICAST-P; D.K. Runyan etal., ), a questionnaire measuring abusive parental disciplinary practices. It was found that PIR-GAS ratings differentiated between the general and the clinical sample, and the dyads with abusive patterns of relationship were identified by both the PIR-GAS and the ICAST-P. Interrater reliability for the PIR-GAS ranged from moderate to excellent. The value of a broader use of tools such as the DC: 0-3R to promote early identification of families at risk for infant and toddler abuse and neglect is discussed.info:eu-repo/semantics/submittedVersio

    Using the Parent-Infant Relationship Global Assessment Scale (PIR-GAS) to identify caregiver – infant/toddler dyads with abusive relationship patterns in six European countries:Identify Abusive Relationships With the PIR-GAS

    Get PDF
    The study examined whether the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood, Revised Edition (DC: 0-3R; ZERO TO THREE, 2005) Parent-Infant Relationship Global Assessment Scale (PIR-GAS) is applicable to six European countries and contributes to the identification of caregiver-infant/toddler dyads with abusive relationship patterns. The sample consisted of 115 dyads with children's ages ranging from 1 to 47 months. Sixty-four dyads were recruited from community settings without known violence problems, and 51 dyads were recruited from clinical settings and already had been identified with violence problems or as being at risk for violence problems. To classify the dyads on the PIR-GAS categories, caregiver-child interactions were video-recorded and coded with observational scales appropriate for child age. To test whether the PIR-GAS allows for reliable identification of dyads with abusive relationship patterns, PIR-GAS ratings were compared with scores on the the International Society for the Prevention of Child Abuse and Neglect's (ISPCAN) Child Abuse Screening Tool-Parental Version (ICAST-P; D.K. Runyan etal., ), a questionnaire measuring abusive parental disciplinary practices. It was found that PIR-GAS ratings differentiated between the general and the clinical sample, and the dyads with abusive patterns of relationship were identified by both the PIR-GAS and the ICAST-P. Interrater reliability for the PIR-GAS ranged from moderate to excellent. The value of a broader use of tools such as the DC: 0-3R to promote early identification of families at risk for infant and toddler abuse and neglect is discussed.info:eu-repo/semantics/submittedVersio

    The ocean sampling day consortium

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    Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

    Psychometric properties of the Spanish version of the Jefferson Scale of Empathy: making sense of the total score through a second order confirmatory factor analysis

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    Background: Empathy is a key aspect of the physician-patient interactions. The Jefferson Scale of Empathy (JSE) is one of the most used empathy measures of medical students. The development of cross-cultural empathy studies depends on valid and reliable translations of the JSE. This study sought to: (1) adapt and assess the psychometric properties in Spanish students of the Spanish JSE validated in Mexican students; (2) test a second order latent factor model. Methods: The Spanish JSE was adapted from the Spanish JSE-S, resulting in a final version of the measure. A non-probabilistic sample of 1104 medical students of two Spanish medical schools completed a socio-demographic and the Spanish JSE-S. Descriptive statistics, along with a confirmatory factor analysis, the average variance extracted (AVE), Cronbach's alphas and composite reliability (CR) coefficients were computed. An independent samples t-test was performed to access sex differences. Results: The Spanish JSE-S demonstrated acceptable to good sensitivity (individual items - except for item 2 - and JSE-S total score: -2.72 < Sk < 0.35 and -0.77 < Ku < 7.85), convergent validity (AVE: between 0.28 and 0.45) and reliability (Cronbach's alphas: between 0.62 and 0.78; CR: between 0.62 and 0.87). The confirmatory factor analysis supported the three-factor solution and the second order latent factor model. Conclusions: The findings provide support for the sensitivity, construct validity and reliability of the adapted Spanish JSE-S with Spanish medical students. Data confirm the hypothesized second order latent factor model. This version may be useful in future research examining empathy in Spanish medical students, as well as in cross-cultural studies.info:eu-repo/semantics/publishedVersio

    Hidden among bromeliads in the Brazilian semiarid: first records of Phyllopezus lutzae for the Caatinga domain and its predation by Tropidurus hispidus

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    During wildlife rescue and monitoring activities, we recorded 142 individuals of Phyllopezus lutzae in the municipalities of Tucano and Nova Soure, state of Bahia, Northeastern Brazil. These records are the first of this species in the Caatinga domain. Moreover, an adult individual of Tropidurus hispidus was recorded attempting to subdue an adult P. lutzae. Beyond to expand the known distribution range of the species, our records show that P. lutzae inhabits an ecological and climate domain different from Atlantic Forest where it was previously known, and that it is a potential prey of T. hispidus.Asociación Herpetológica Argentin
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