Bringing tacit knowledge back to contributory and interactional expertise: A reply to Goddiksen

We analyse a recent paper by Goddiksen (2014) where the author raises questions about the relationship between authorship, attribution and Collins & Evans' concept of contributory and interactional expertise. We then highlight recent empirical work in the sociology of climate change science that has made similar points in order to clarify how authorship, division of labour and contribution are handled in real scientific settings. Despite this, Goddiksen's critique of both contributory and interactional expertise is ultimately ineffective because it rests on a misguided attempt to de-socialise these concepts. We conclude by stressing the importance of collective tacit knowledge acquisition through immersion as a critical step in becoming a full-blown contributory or interactional expert.     

Memory corticalization triggered by REM sleep: mechanisms of cellular and systems consolidation

Once viewed as a passive physiological state, sleep is a heterogeneous and complex sequence of brain states with essential effects on synaptic plasticity and neuronal functioning. Rapid-eye-movement (REM) sleep has been shown to promote calcium-dependent plasticity in principal neurons of the cerebral cortex, both during memory consolidation in adults and during post-natal development. This article reviews the plasticity mechanisms triggered by REM sleep, with a focus on the emerging role of kinases and immediate-early genes for the progressive corticalization of hippocampus-dependent memories. The body of evidence suggests that memory corticalization triggered by REM sleep is a systemic phenomenon with cellular and molecular causes.     

Oncogenic IL7R gain-of-function mutations in childhood T-cell acute lymphoblastic leukemia

Interleukin 7 (IL-7) and its receptor, formed by IL-7Rα (encoded by IL7R) and γc, are essential for normal T-cell development and homeostasis. Here we show that IL7R is an oncogene mutated in T-cell acute lymphoblastic leukemia (T-ALL). We find that 9% of individuals with T-ALL have somatic gain-of-function IL7R exon 6 mutations. In most cases, these IL7R mutations introduce an unpaired cysteine in the extracellular juxtamembrane-transmembrane region and promote de novo formation of intermolecular disulfide bonds between mutant IL-7Rα subunits, thereby driving constitutive signaling via JAK1 and independently of IL-7, γc or JAK3. IL7R mutations induce a gene expression profile partially resembling that provoked by IL-7 and are enriched in the T-ALL subgroup comprising TLX3 rearranged and HOXA deregulated cases. Notably, IL7R mutations promote cell transformation and tumor formation. Overall, our findings indicate that IL7R mutational activation is involved in human T-cell leukemogenesis, paving the way for therapeutic targeting of IL-7R-mediated signaling in T-ALL.     

Your Vision or My Model? Lessons from Participatory Land Use Scenario Development on a European Scale

Participatory processes in scenario development have received increasing attention throughout the last years. Combining qualitative stakeholder and quantitative expert information (i.e. modelling) offers unique opportunities to mix good data, scientific rigour, imagination and expertise from different perspectives. However, this task is all but easy as it requires a careful balancing of approaches and an acceptance of different levels of knowledge and trust in different methods across disciplinary boundaries. In spite of a growing body of literature we are still in the early stages of learning how to deal effectively with participatory scenario development. In the PRELUDE project of the European Environment Agency a relatively far-reaching participatory approach to scenario development was applied: a group of stakeholders from across Europe was given full responsibility to develop long-term alternative land use scenarios in cooperation with experts and modellers. The scenarios have been used in a formal outreach process with key clients and stakeholders at the European and Member State level afterwards. The aim of this paper is to document the methods used, analyse their strengths and weaknesses and draw some general conclusions regarding participatory processes in scenario development. This paper argues that in future scenario development more attention needs to be paid to strengthen the integration of qualitative and quantitative analysis. A set of compelling and coherent storylines can effectively trigger strategic conversations among policy-makers and key stakeholders about potential future developments and related response strategies. A weak integration with quantitative results can undermine this outcome, which is one of the ultimate objectives of any scenario exercise.

Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma

Neuroblastoma, a tumour derived from the peripheral sympathetic nervous system, is one of the most frequent solid tumours in childhood. It usually occurs sporadically but familial cases are observed, with a subset of cases occurring in association with congenital malformations of the neural crest being linked to germline mutations of the PHOX2B gene. Here we conducted genome-wide comparative genomic hybridization analysis on a large series of neuroblastomas. Copy number increase at the locus encoding the anaplastic lymphoma kinase (ALK) tyrosine kinase receptor was observed recurrently. One particularly informative case presented a high-level gene amplification that was strictly limited to ALK, indicating that this gene may contribute on its own to neuroblastoma development. Through subsequent direct sequencing of cell lines and primary tumour DNAs we identified somatic mutations of the ALK kinase domain that mainly clustered in two hotspots. Germline mutations were observed in two neuroblastoma families, indicating that ALK is a neuroblastoma predisposition gene. Mutated ALK proteins were overexpressed, hyperphosphorylated and showed constitutive kinase activity. The knockdown of ALK expression in ALK-mutated cells, but also in cell lines overexpressing a wild-type ALK, led to a marked decrease of cell proliferation. Altogether, these data identify ALK as a critical player in neuroblastoma development that may hence represent a very attractive therapeutic target in this disease that is still frequently fatal with current treatments.     

Interpretation of the sonic hedgehog morphogen gradient by a temporal adaptation mechanism

Morphogens act in developing tissues to control the spatial arrangement of cellular differentiation. The activity of a morphogen has generally been viewed as a concentration-dependent response to a diffusible signal, but the duration of morphogen signalling can also affect cellular responses. One such example is the morphogen sonic hedgehog (SHH). In the vertebrate central nervous system and limbs, the pattern of cellular differentiation is controlled by both the amount and the time of SHH exposure. How these two parameters are interpreted at a cellular level has been unclear. Here we provide evidence that changing the concentration or duration of SHH has an equivalent effect on intracellular signalling. Chick neural cells convert different concentrations of SHH into time-limited periods of signal transduction, such that signal duration is proportional to SHH concentration. This depends on the gradual desensitization of cells to ongoing SHH exposure, mediated by the SHH-dependent upregulation of patched 1 (PTC1), a ligand-binding inhibitor of SHH signalling. Thus, in addition to its role in shaping the SHH gradient, PTC1 participates cell autonomously in gradient sensing. Together, the data reveal a novel strategy for morphogen interpretation, in which the temporal adaptation of cells to a morphogen integrates the concentration and duration of a signal to control differential gene expression.