Our ability to select relevant information from the environment is limited by the resolution of attention – i.e., the minimum size of the region that can be selected. Neural mechanisms that underlie this limit and its development are not yet understood. Functional MRI was performed during an object tracking task in 7- and 11-year-old children, and in young adults. Object tracking activated canonical fronto-parietal attention systems and motion-sensitive area MT in children as young as 7 years. Object tracking performance improved (...) with age, together with stronger recruitment of parietal attention areas and a shift from low-level to higher-level visual areas. Increasing the required resolution of spatial attention – which was implemented by varying the distance between target and distractors in the object tracking task – led to activation increases in fronto-insular cortex, medial frontal cortex including anterior cingulate cortex (ACC) and supplementary motor area, superior colliculi, and thalamus. This core circuitry for attentional precision was recruited by all age groups, but ACC showed an age-related activation reduction. Our results suggest that age-related improvements in selective visual attention and in the resolution of attention are characterized by an increased use of more functionally specialized brain regions during the course of development. (shrink)

The severe hereditary progeroid disorder Cockayne syndrome is a consequence of a defective transcription‐coupled repair (TCR) pathway. This special mode of DNA repair aids a RNA polymerase that is stalled by a DNA lesion in the template and ensures efficient DNA repair to permit resumption of transcription and prevent cell death. Although some key players in TCR, such as the Cockayne syndrome A (CSA) and B (CSB) proteins have been identified, the exact molecular mechanism still remains illusive. A recent report (...) provides new unexpected insights into TCR in yeast.1 The identification and characterisation of a novel protein co‐purifying with the yeast homologue of CSB (Rad26) imposes reassessment of our current understanding of TCR in yeast. What about humans? BioEssays 24:780–784, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

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Meta-theories, base-theories and theories of practice in Pratical Theology The problem of meta-theories and base-theories, their interaction and the influence of each on the scientific process, have widely been debated in practical theology. In South Africa two meta-theories namely the system- theory together with the theory that social science is busy with the study of actions, are having the greater deal of attention. The purpose of this article is to point out the fact that an early and absolute choice of (...) particular meta-theories, restricts the work of practical theology because it will influence your base-theories, and can weaken the theological content of practical theology. An attempt is made to offer a model by which the interaction between, meta-theories, base-theories and theories of practice can he understood and which can also help the theologian, busy with practical theology, to steer clear of problems and understand the meta- influences in his own scientific work. (shrink)

Postnatally, heart muscle cells almost completely lose their ability to divide, which makes their loss after trauma irreversible. Potential repair by cell grafting or mobilizing endogenous cells is of particular interest for possible treatments for heart disease, where the poor capacity for cardiomyocyte proliferation probably contributes to the irreversibility of heart failure. Knowledge of the molecular mechanisms that underly formation of heart muscle cells might provide opportunities to repair the diseased heart by induction of (trans) differentiation of endogenous or exogenous (...) cells into heart muscle cells. We briefly review the molecular mechanisms involved in early development of the linear heart tube by differentiation of mesodermal cells into heart muscle cells. Because the initial heart tube does not comprise all the cardiac compartments present in the adult heart, heart muscle cells are added to the distal borders of the tube and within the tube. At both distal borders, mesodermal cell are recruited into the cardiac lineage and, within the heart tube, muscular septa are formed. In this review, the relative late additions of heart muscle cells to the linear heart tube are described and the potential underlying molecular mechanisms are discussed. BioEssays 26:248–261, 2004. Wiley Periodicals, Inc. (shrink)

© 2015 Elsevier Inc.Postnatal organogenesis occurs in an immune competent environment and is tightly controlled by interplay between positive and negative regulators. Innate immune cells have beneficial roles in postnatal tissue remodeling, but roles for the adaptive immune system are currently unexplored. Here we show that adaptive immune responses participate in the normal postnatal development of a non-lymphoid epithelial tissue. Since the mammary gland is the only organ developing predominantly after birth, we utilized it as a powerful system to study (...) adaptive immune regulation of organogenesis. We found that antigen-mediated interactions between mammary antigen-presenting cells and interferon-γ -producing CD4+ T helper 1 cells participate in MG postnatal organogenesis as negative regulators, locally orchestrating epithelial rearrangement. IFNγ then affects luminal lineage differentiation. This function of adaptive immune responses, regulating normal development, changes the paradigm for studying players of postnatal organogenesis and provides insights into immune surveillance and cancer transformation. Plaks et al. (shrink)

Background Genuine uncertainty on superiority of one intervention over the other is called equipoise. Physician-investigators in randomized controlled trials need equipoise at least in studies with more than minimal risks. Ideally, this equipoise is also present in patient-participants. In pediatrics, data on equipoise are lacking. We hypothesize that 1) lack of equipoise at enrolment among parents may reduce recruitment; 2) lack of equipoise during participation may reduce retention in patients assigned to a less favoured treatment-strategy. Methods We compared preferences of (...) parents/patients at enrolment, documented by a questionnaire, with preferences developed during follow-up by an interview-study to investigate equipoise of child-participants and parents in the BeSt-for-Kids-study. This trial in new-onset Juvenile Idiopathic Arthritis-patients consists of three strategies. One strategy comprises initial treatment with a biological disease-modifying-antirheumatic-drug, currently not standard-of-care. Semi-structured interviews were conducted with 23 parents and 7 patients, median 11 months after enrolment. Results Initially most parents and children were not in equipoise. Parents/patients who refused participation, regularly declined due to specific preferences. Many participating families preferred the biological-first-strategy. They participated to have a chance for this initial treatment, and would even consider stopping trial-participation when not randomized for it. Their conviction of superiority of the biological-first strategy was based on knowledge from internet and close relations. According to four parents, the physician-investigator preferred the biological-first-strategy, but the majority stated that she had no preferred strategy. In phase 2, preferences tended to change to the treatment actually received. Conclusions Lack of equipoise during enrolment did not reduce study recruitment, mainly due to the fact that preferred treatment was only available within the study. Still, when developing a trial it is important to evaluate whether the physicians’ research question is in line with preferences of the patient-group. By exploring so-called ‘informed patient-group’-equipoise, successful recruitment may be enhanced and bias avoided. In our study, lack of equipoise during trial-participation did not reduce retention in those assigned to a less favoured option. We observed a change for preference towards treatment actually received, possibly explained by comparable outcomes in all three arms. (shrink)

How can new drug lead suggestions beinferred from neurophysiological models? This paperaddresses this question based on a case study ofresearch into Parkinson''s disease at the GroningenUniversity Department of Pharmacy. It is argued thatneurophysiological box-and-arrow models can beunderstood as qualitative differential equationmodels. An inference task is defined to helpunderstand and possibly aid the discovery andexplanation of new drug lead suggestions.

This paper explores structuralism as a way to model theories from scientific practice. As a case study I analyzed a theory about the dynamics of the basal ganglia, a part of the brain that is involved in Parkinson's disease. After introducing the case study I explore how to structurally represent qualitative assumptions about disease, intervention and dynamical systems in general. I further explicate the structure of the basal ganglia theory in detail, how it explains Parkinson's disease and how it implies (...) treatments. I close with a consideration of how a structuralist representation could be useful in practice to explore and develop theories with the aid of a computer. (shrink)

Within current debates about the future impact of Artificial Intelligence on human society, roughly three different perspectives can be recognised: the technology-centric perspective, claiming that AI will soon outperform humankind in all areas, and that the primary threat for humankind is superintelligence; the human-centric perspective, claiming that humans will always remain superior to AI when it comes to social and societal aspects, and that the main threat of AI is that humankind’s social nature is overlooked in technological designs; and the (...) collective intelligence-centric perspective, claiming that true intelligence lies in the collective of intelligent agents, both human and artificial, and that the main threat for humankind is that technological designs create problems at the collective, systemic level that are hard to oversee and control. The current paper offers the following contributions: a clear description for each of the three perspectives, along with their history and background; an analysis and interpretation of current applications of AI in human society according to each of the three perspectives, thereby disentangling miscommunication in the debate concerning threats of AI; and a new integrated and comprehensive research design framework that addresses all aspects of the above three perspectives, and includes principles that support developers to reflect and anticipate upon potential effects of AI in society. (shrink)

Processing information in the context of personal survival scenarios elicits a memory advantage, relative to other rich encoding conditions such as self-referencing. However, previous research is unable to distinguish between the influence of survival and self-reference because personal survival is a self-referent encoding context. To resolve this issue, participants in the current study processed items in the context of their own survival and a familiar other person’s survival, as well as in a semantic context. Recognition memory for the items revealed (...) that personal survival elicited a memory advantage relative to semantic encoding, whereas other-survival did not. These findings reinforce suggestions that the survival effect is closely tied with self-referential encoding, ensuring that fitness information of potential importance to self is successfully retained in memory. (shrink)

Situated normativity is the ability of skilled individuals to distinguish better from worse, adequate from inadequate, appropriate from inappropriate, or correct from incorrect in the context of a particular situation. Situated normativity consists in a situated appreciation expressed in normative behaviour, and can be experienced as a bodily affective tension that motivates a skilled individual to act on particular possibilities for action offered by a concrete situation. The concept of situated normativity has so far primarily been discussed in the context (...) of skilled unreflective action. In this paper, we aim to explore and sketch the role of the concept of situated normativity in characterising more reflective forms of normativity. The goal of the paper is two-fold: first, by showing more reflective forms of normativity to be continuous with unreflective situated normativity, we bring these reflective forms into the reach of embodied accounts of cognition; and second, by extending the concept of situated normativity, new light is thrown on questions regarding reflective forms of cognition. We show that sociomaterial aspects of situations are crucial for understanding more reflective forms of normativity. We also shed light on the important question of how explicit rules can compel people to behave in particular ways. (shrink)