187 research outputs found
A time for learning: representations of time and the temporal dimensions of learning through the lifecourse
Based on findings from a large-scale longitudinal study into the learning biographies of adults, this paper focuses on the different representations of time in the interview data. The paper discusses three such representations: chronological time, narrative time, and generational time. The authors show how different notions of time operate within the construction of life stories. They also analyse the ways in which different representations of time impact upon and serve as resources for reflection on and learning from life, thus contributing to understanding the complex relationships between biography, life and time. (DIPF/Orig.)
Learning from life in the learning economy: The role of narrative
From introduction: The shift from adult education to lifelong learning has not only impacted on the role and position of the adult educator, but has also had a profound effect on the legitimation of the learning of adults. Whereas adult education has historically been connected with learning for personal development and empowerment and learning for social inclusiveness and democratic understanding and activity (see Aspin & Chapman 2001), the rise of the ‘learning paradigm’ (Martin 2006; Biesta 2006a) has been accompanied by an emphasis on learning for economic progress and development. This is not only visible in policy discourse but has also influenced the allocation of public funding for the learning of adults and thus has had a real effect on the kinds of education adults are able to engage in. The rise of the ‘learning paradigm’ can be seen as part of a struggle over the definition of learning: a struggle over what counts as (worthwhile) learning and a struggle over who is allowed to define what (worthwhile) learning is (see Biesta 2006b). In this context an important task for adult education researchers is to highlight the significance of the broad range of learning processes and practices that occur in the lives of adults so as to show that there is more to learning than what is acknowledged in the economic definition of lifelong learning. Doing this has been one of the main ambitions of the Learning Lives project, a 3-year longitudinal study into the learning biographies of about 120 adults of 25 and older (see www.learninglives.org). The research was based upon a series of open-ended interviews in which we invited participants to talk about their lives and the role of learning in it, both retrospectively (using a life-history approach) and in relation to events in their lives over the duration of the project. In this paper we focus on one particular aspect of the learning we encountered in the project, viz., the way in which adults learn from their lives. Our interest in this was prompted by the fact that upon reading and analysing the life-stories of participants we found that in a significant number of cases these stories articulated that participants had reached some kind of insight or understanding about their lives, themselves and their position in the world. The stories evidenced, in other words, that the participants had learned something from their lives. We also found that this learning had had an impact on the ways in which the participants led their lives. We became particularly interested in the role of stories and storying in such learning processes and in possible relationships between the ‘narrative quality’ of life-stories and their potential for learning and action. For our analysis we engaged with literature on narrative in the human and social sciences (Polkinghorne 1988; Bruner 1990; Czarniawska 2004), with the emerging body of work on narrative learning in adult education (Rossiter 1999; Rossiter and Clark 2007), and with research and theory on biographical learning (Alheit 1995; Alheit & Dausien 2002). In this paper we present some of the findings from our analysis and reflect upon their significance for adult learning in the learning economy
Into the future with little past: exploring mental time travel in a patient with damage to the mammillary bodies/fornix
Objective: Remembering the past and imaging the future are both manifestations of ‘mental time travel’. These processes have been found to be impaired in patients with bilateral hippocampal lesions. Here, we examined the question of whether future thinking is affected by other Papez circuit lesions, namely: damage to the mammillary bodies/fornix. Method: Case (SL) was a 43-year-old woman who developed dense anterograde and retrograde amnesia suddenly, as a result of Wernicke–Korsakoff’s syndrome. A region of interest volumetric Magnetic resonance imaging (MRI) analysis was performed. We assessed past and future thinking in SL and 11 control subjects of similar age and education with the adapted Autobiographical Interview (AI). Participants also completed a battery of neuropsychological tests. Results: Volumetric MRI analyses revealed severely reduced fornix and mammillary body volumes, but intact hippocampi. SL showed substantial, albeit temporally graded retrograde memory deficits on the adapted AI. Strikingly, whilst SL could not provide any specific details of events from the past two weeks or past two years and had impaired recall of events from her late 30s, her descriptions of potential future events were normal in number of event details and plausibility. Conclusions: This dissociation of past and future events’ performance after mammillary body and fornix damage is at odds with the findings of the majority of patients with adult onset hippocampal amnesia. It suggests that these non-hippocampal regions of the Papez circuit are only critical for past event retrieval and not for the generation of possible future events
Memory B cells, but not long-lived plasma cells, possess antigen specificities for viral escape mutants
Memory B cells have the unique capacity to recognize variants of West Nile virus, likely providing protection against mutant viruses that escape antibody neutralization
Regulation of L-Selectin–mediated Rolling through Receptor Dimerization
L-selectin binding activity for its ligand expressed by vascular endothelium is rapidly and transiently increased after leukocyte activation. To identify mechanisms for upregulation and assess how this influences leukocyte/endothelial cell interactions, cell-surface dimers of L-selectin were induced using the coumermycin–GyrB dimerization strategy for cross-linking L-selectin cytoplasmic domains in L-selectin cDNA-transfected lymphoblastoid cells. Coumermycin- induced L-selectin dimerization resulted in an approximately fourfold increase in binding of phosphomanan monoester core complex (PPME), a natural mimic of an L-selectin ligand, comparable to that observed after leukocyte activation. Moreover, L-selectin dimerization significantly increased (by ∼700%) the number of lymphocytes rolling on vascular endothelium under a broad range of physiological shear stresses, and significantly slowed their rolling velocities. Therefore, L-selectin dimerization may explain the rapid increase in ligand binding activity that occurs after leukocyte activation and may directly influence leukocyte migration to peripheral lymphoid tissues or to sites of inflammation. Inducible oligomerization may also be a common mechanism for rapidly upregulating the adhesive or ligand-binding function of other cell-surface receptors
CD20 and CD19 targeted vectors induce minimal activation of resting B lymphocytes
B lymphocytes are an important cell population of the immune system. However, until recently it was not possible to transduce resting B lymphocytes with retro- or lentiviral vectors, making them unsusceptible for genetic manipulations by these vectors. Lately, we demonstrated that lentiviral vectors pseudotyped with modified measles virus (MV) glycoproteins hemagglutinin, responsible for receptor recognition, and fusion protein were able to overcome this transduction block. They use either the natural MV receptors, CD46 and signaling lymphocyte activation molecule (SLAM), for cell entry (MV-LV) or the vector particles were further modified to selectively enter via the CD20 molecule, which is exclusively expressed on B lymphocytes (CD20-LV). It has been shown previously that transduction by MV-LV does not induce B lymphocyte activation. However, if this is also true for CD20-LV is still unknown. Here, we generated a vector specific for another B lymphocyte marker, CD19, and compared its ability to transduce resting B lymphocytes with CD20-LV. The vector (CD19ds-LV) was able to stably transduce unstimulated B lymphocytes, albeit with a reduced efficiency of about 10% compared to CD20-LV, which transduced about 30% of the cells. Since CD20 as well as CD19 are closely linked to the B lymphocyte activation pathway, we investigated if engagement of CD20 or CD19 molecules by the vector particles induces activating stimuli in resting B lymphocytes. Although, activation of B lymphocytes often involves calcium influx, we did not detect elevated calcium levels. However, the activation marker CD71 was substantially up-regulated upon CD20-LV transduction and most importantly, B lymphocytes transduced with CD20-LV or CD19ds-LV entered the G1b phase of cell cycle, whereas untransduced or MV-LV transduced B lymphocytes remained in G0. Hence, CD20 and CD19 targeting vectors induce activating stimuli in resting B lymphocytes, which most likely renders them susceptible for lentiviral vector transduction
Identification of a dna methylation episignature in the 22q11.2 deletion syndrome
The 22q11.2 deletion syndrome (22q11.2DS) is the most common genomic disorder in humans and is the result of a recurrent 1.5 to 2.5 Mb deletion, encompassing approximately 20–40 genes, respectively. The clinical presentation of the typical deletion includes: Velocardiofacial, Di George, Opitz G/BBB and Conotruncalanomaly face syndromes. Atypical deletions (proximal, distal or nested) are rare and characterized mainly by normal phenotype or mild intellectual disability and variable clinical features. The pathogenetic mechanisms underlying this disorder are not completely understood. Because the 22q11.2 region harbours genes coding for transcriptional factors and chromatin remodelers, in this study, we performed analysis of genome‐wide DNA methylation of peripheral blood from 49 patients with 22q11.2DS using the Illumina Infinium Methylation EPIC bead chip arrays. This cohort comprises 43 typical, 2 proximal and 4 distal deletions. We demonstrated the evidence of a unique and highly specific episignature in all typical and proximal 22q11.2DS. The sensitivity and specificity of this signature was further confirmed by comparing it to over 1500 patients with other neurodevelopmental disorders with known episignatures. Mapping the 22q11.2DS DNA methylation episignature provides both novel insights into the molecular pathogenesis of this disorder and an effective tool in the molecular diagnosis of 22q11.2DS
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