Understanding interactions in face-to-face and remote undergraduate science laboratories

This paper reviews the ways in which interactions have been studied, and the findings of such studies, in science education in both face-to-face and remote laboratories. Guided by a systematic selection process, 27 directly relevant articles were analysed based on three categories: the instruments used for measuring interactions, the research findings on student interactions, and the theoretical frameworks used in the studies of student interactions. In face-to-face laboratories, instruments for measuring interactions and the characterisation of the nature of interactions were prominent. For remote laboratories, the analysis of direct interactions was found to be lacking. Instead, studies of remote laboratories were mainly concerned with their practical scope. In addition, it is found that only a limited number of theoretical frameworks have been developed and applied in the research design. Existent theories are summarised and possible theoretical frameworks that may be implemented in studies of interactions in undergraduate laboratories are proposed. Finally, future directions for research on the interrelationship between student interactions and laboratory learning are suggested

Science teachers’ experiences of inquiry-based learning through a serious game:a phenomenographic perspective

This study employed a phenomenographic approach to investigate science teachers’ conceptions of inquiry-based learning through a serious game. Simaula is a prototype game designed and used as a virtual practicum for eliciting understandings on how in-game inquiry was appeared to, or experienced by, the participating teachers. Group interviews with 20 secondary education science teachers revealed four qualitatively different ways of experiencing inquiry-based learning through Simaula: (a) as uncovering insights about student’s learning needs, interests and emotions; (b) as generating ideas and concepts for meaningful inquiry; (c) as a set of operations for designing and carrying out scientific research; and (d) as authentic inquiry for enabling knowledge building processes. Seven dimensions of variation have been identified viewed as contextual influences on conceptions of in-game inquiry constituting discernment of: epistemic inquiry-based learning modes; role of teacher; role of student; game-play focus; core mechanics focus; feedback and progress mechanics and game uncertainty. The results illuminated a partial in-game inquiry approach with distinct epistemic modes from developing empathy and meaning making to knowledge construction and knowledge building. The findings also indicated that game design elements played central role in shaping conceptions of in-game inquiry from focusing on rules and logic as means to completing the game’s level to understanding the complexity of core mechanics for developing and transferring in-game inquiry to the real classroom. This insinuates that distinct game design properties may be considered in terms of extending intrinsic in-game inquiry experiences to actual in-class inquiry practice

Inhibition of Aurora A in response to DNA damage

Mitotic kinases are the ultimate target of pathways sensing genotoxic damage and impinging on the cell cycle machinery. Here, we provide evidence that Aurora A (AurA) was inhibited upon generation of double-strand breaks in DNA. We demonstrate that AurA was not downstream of CDK1 and that inhibition of AurA and CDK1 by DNA damage occurred independently. Using a cell line functionally deficient in Chk2, a selective Chk1 inhibitor and siRNA to Chk1, we show that DNA-damage signals were delivered to AurA through a Chk1-dependent pathway. With regard to the molecular mechanism of AurA inhibition, we found that the point mutation Ser(342)>Ala rendered AurA resistant to inhibition by DNA damage. By means of two distinct approaches we examined the impact of reconstitution of AurA activity in DNA-damaged cells: (i) transient expression of wild-type and Ser(342)>Ala mutant, but not kinase-dead, AurA led to bypass of the DNA damage block; (ii) direct transduction of highly active wt-AurA into G2 arrested cells precisely after induction of DNA damage resulted in mitotic entry. We show that the mechanism through which AurA allowed entry into mitosis was reactivation of CDK1, thus indicating that AurA plays a key role upstream of CDK1. A model depicting the possible role of AurA at the onset of mitosis and upon DNA damage is presented

Aurora-A site specificity: a study with synthetic peptide substrates

AurA (Aurora-A) is a ubiquitous protein kinase regulating entry into mitosis and shown to promote transformation upon overexpression. In order to gain information on the structural features determining its substrate specificity, we assayed human recombinant AurA on a variety of phosphoacceptor peptide substrates including a series of properly modified derivatives of the Kemptide (ALRRASLGAA). The data presented here show that AurA is a basophilic Ser/Thr protein kinase recognizing the consensus R/K/N-R-X-S/T-B, where B denotes any hydrophobic residue with the exception of Pro. We show that the presence of a Pro at position n+1 fully abrogates phosphorylation of the peptide substrate. Although the consensus for AurA is reminiscent of that of PKA (protein kinase A), it significantly differs from the latter for a much more stringent dependence on the hydrophobic residue at n+1 and for its tolerance of residues other than Arg at position n−3. Based on the finding that the peptide ALKRASLGAA is not a substrate of PKA while still providing a sensitive assay of AurA activity, we suggest that this peptide may be used for differential screening of the two kinases. We have further validated the AurA consensus by generating a peptide (APSSRRTT(288)LCGT) that comprises the main AurA autophosphorylation site and by showing that AurA phosphorylated this peptide exclusively at one site fulfilling its consensus (Thr(288)). Moreover, we show that AurA could autophosphorylate at Thr(288) through an intermolecular mechanism of reaction and that, in vivo, PKA was not involved with Thr(288) phosphorylation. The evidence obtained in the present study provides a rational tool for predicting AurA sites in potential substrates of physiological significance

Synthetic lethality of PARP inhibition in cancers lacking BRCA1 and BRCA2 mutations

Utilizing the concept of synthetic lethality has provided new opportunities for the development of targeted therapies, by allowing the targeting of loss of function genetic aberrations. In cancer cells with BRCA1 or BRCA2 loss of function, which harbor deficiency of DNA repair by homologous recombination, inhibition of PARP1 enzymatic activity leads to an accumulation of single strand breaks that are converted to double strand breaks but cannot be repaired by homologous recombination. Inhibition of PARP has therefore been advanced as a novel targeted therapy for cancers harboring BRCA1/2 mutations. Preclinical and preliminary clinical evidence, however, suggests a potentially broader scope for PARP inhibitors. Loss of function of various proteins involved in double strand break repair other than BRCA1/2 has been suggested to be synthetically lethal with PARP inhibition. Inactivation of these genes has been reported in a subset of human cancers and might therefore constitute predictive biomarkers for PARP inhibition. Here we discuss the evidence that the clinical use of PARP inhibition may be broader than targeting of cancers in BRCA1/2 germ-line mutation carriers