Response Format, Not Semantic Activation, Influences the Failed Retrieval Effect.

In educational settings, tests are mainly used to measure the extent to which learners' knowledge and skill have been acquired. However, the act of taking a test also promotes learning itself. In particular, making errors on tests (i.e., searching for erroneous information) promotes learning. This is called the "failed retrieval effect" (FRE) and has been the subject of considerable study. Previous research shows that enhanced learning does not occur if feedback correcting an error is delayed. This is attributed to the relative absence of activated information. In this study, we manipulated both the amount of information to be retrieved prior to learning and the delay time until feedback is given to investigate their effects on learning. As a result, even when multiple incorrect answers were given to increase the degree of semantic activation, learning was not promoted beyond that found with traditional procedures that rely on only one incorrect response. The timing of feedback (immediate, short-delay, long-delay) also did not impact FRE. However, the manipulation of response format for erroneous information resulted in degraded performance when responses were typed and feedback was delayed. Based on this result, we suggested that the failed retrieval effect was not affected by semantic activation at the time of retrieval but was affected by response format. Moreover, the processing necessary for typing may affect FRE under the delayed feedback condition.

Imaging scoring systems for preoperative molecular diagnoses of lower-grade gliomas.

Recent advance in molecular characterization of gliomas showed that patient prognosis and/or tumor chemosensitivity correlate with certain molecular signatures; however, this information is available only after tumor resection. If molecular information is available by routine radiological examinations, surgical strategy as well as overall treatment strategy could be designed preoperatively.With the aim to establish an imaging scoring system for preoperative diagnosis of molecular status in lower-grade gliomas (WHO grade 2 or 3, LrGGs), we investigated 8 imaging features available on routine CT and MRI in 45 LGGs (discovery cohort) and compared them with the status of 1p/19q codeletion, IDH mutations, and MGMT promoter methylation. The scoring systems were established based on the imaging features significantly associated with each molecular signature, and were tested in the another 52 LrGGs (validation cohort).For prediction of 1p/19q codeletion, the scoring system is composed of calcification, indistinct tumor border on T1, paramagnetic susceptibility effect on T1, and cystic component on FLAIR. For prediction of MGMT promoter methylation, the scoring system is composed of indistinct tumor border, surface localization (FLAIR), and cystic component. The scoring system for prediction of IDH status was not established. The 1p/19q score ≥ 3 showed PPV of 96.2% and specificity of 98.1%, and the MGMT methylation score ≥ 2 showed PPV of 77.4% and specificity of 67.6% in the entire cohort.These scoring systems based on widely available imaging information may help to preoperatively design personalized treatment in patients with LrGG.

Electrophysiological decomposition of attentional factors on the hypercorrection effect of false lexical representations.

False memories endorsed with higher confidence are more likely to be corrected by feedback than those endorsed with lower confidence (hypercorrection effect). Errors made with high confidence and correct responses made with low confidence are both associated with large meta-memory mismatches. Therefore, they both represent a type of unexpected event which automatically captures participant attention, such that correct information provided via feedback is well-encoded. On the other hand, a study that measured participants' perceived practical value for items suggested that voluntary allocation of attention might involve the hypercorrection effect. The present study involved a lexical learning task with 28 undergraduate student participants and measurement of automatic and voluntary attentional allocations via P3a/novelty P3 and P3b respectively, both of which are event-related potentials (ERPs). Behavioral results replicated the hypercorrection effect in a lexical learning task and showed modulation of the effect with regard to perceived practical value. In addition, ERP measurement results demonstrated that both automatic and voluntary allocations of attentional resources were independently involved in the hypercorrection phenomenon.

Does delayed corrective feedback enhance acquisition of correct information?

Many studies concerned with misinformation correction during learning report that delayed corrective feedback is superior to immediate feedback. However, the mechanism for this effect has not been confirmed. The interference-perseveration theory predicts that immediate feedback following participants' wrong responses elicits proactive interference that deteriorates acquisition of feedback information. In contrast, delayed feedback following errors leads to participants' forgetting these errors during the delay period; consequently, in the latter, interference should decline leading to superior acquisition of corrective information. However, results of these studies have been inconsistent. The present study manipulated whether initial errors were visually cued before feedback (no error-cueing, error-cueing) along with the timing of the feedback (immediate, delayed). The interference-perseveration theory predicts that when errors are not cued, delayed feedback should result in superior acquisition of correct information compared to immediate feedback. When errors are cued, proactive interference should effect a deterioration in acquisition of corrective feedback. Results confirmed neither of these predictions, thus challenging the interference-perseveration hypothesis. Moreover, additional analysis suggested that memory for errors has the ability to enhance the retention of correct answers and it does not hinder recall.

Knockdown of the coenzyme Q synthesis gene Smed-dlp1 affects planarian regeneration and tissue homeostasis.

The freshwater planarian is a model organism used to study tissue regeneration that occupies an important position among multicellular organisms. Planarian genomic databases have led to the identification of genes that are required for regeneration, with implications for their roles in its underlying mechanism. Coenzyme Q (CoQ) is a fundamental lipophilic molecule that is synthesized and expressed in every cell of every organism. Furthermore, CoQ levels affect development, life span, disease and aging in nematodes and mice. Because CoQ can be ingested in food, it has been used in preventive nutrition. In this study, we investigated the role of CoQ in planarian regeneration. Planarians synthesize both CoQ9 and rhodoquinone 9 (RQ9). Knockdown of Smed-dlp1, a trans-prenyltransferase gene that encodes an enzyme that synthesizes the CoQ side chain, led to a decrease in CoQ9 and RQ9 levels. However, ATP levels did not consistently decrease in these animals. Knockdown animals exhibited tissue regression and curling. The number of mitotic cells decreased in Smed-dlp1 (RNAi) animals. These results suggested a failure in physiological cell turnover and stem cell function. Accordingly, regenerating planarians died from lysis or exhibited delayed regeneration. Interestingly, the observed phenotypes were partially rescued by ingesting food supplemented with α-tocopherol. Taken together, our results suggest that oxidative stress induced by reduced CoQ9 levels affects planarian regeneration and tissue homeostasis.

Volumetric characterization of ester- and ether-linked lipid bilayers by pressure perturbation calorimetry and densitometry.

We investigated the thermotropic volume behavior of dimyristoylphosphatidylcholine (DMPC), dipalmitoylphosphatidylcholine (DPPC) and dihexadecylphosphatidylcholine (DHPC) membranes using pressure perturbation calorimetry (PPC) and densitometry. The ln φ(2) vs temperature curves (φ(2): apparent molar volume of phospholipid) obtained from the PPC data using an analysis method that we developed agreed with the results from the density measurements for these lipids within the relative difference of about 0.62%. From those curves, the volume changes with the main transition were estimated at 18.0±0.49, 23.5±2.33 and 23.0±0.33 cm(3) mol(-1) for DMPC, DPPC and DHPC, respectively. For DPPC and DMPC, the average volume per methylene group of the hydrocarbon chains v(CH2) calculated by referring to the procedure by Nagle and Wilkinson was consistent with the previous result, which indicates that the DPPC bilayer in the gel state has denser hydrophobic bilayer core than the DMPC bilayer. For DHPC, the volume of the headgroup region v(H) was calculated to be 244 Å(3) by assuming that v(CH2) of DHPC equals that of DPPC above 45°C. This value was comparable to that of DPPC when the volume of the carbonyl groups was considered, which may signify that there is no significant conformational difference in the polar headgroups of both phospholipids. However, it was suggested from the consideration on v(H) of DHPC at 20°C that expansion of the headgroup region should occur as the interdigitated structure is formed, which means some conformational change of the headgroup region is induced by the interdigitation.

Overexpression of taurine transporter in Chinese hamster ovary cells can enhance cell viability and product yield, while promoting glutamine consumption.

Transporters mediate the uptake of nutrients such as amino acids and the excretion of metabolites. The fact that transporters play crucial roles in regulating cell metabolism suggests that they might be useful targets for cell engineering to enhance the yield and/or quality of monoclonal antibody (MAb) produced by CHO cells. The taurine transporter (TAUT) is stably expressed in CHO-DXB11 cells and is upregulated late in the culture period. We found that forcing the overexpression of TAUT delayed apoptotic cell death, extending the culture period. Thus, under fed-batch small-culture conditions, CHO cells that expressed pHyg-TAUT plasmid (TAUT/CHO cells), but not those that contained the null plasmid pHyg (HYG/CHO cells), produced more MAb (P < 0.01) and less lactate (P < 0.05). In a 1-L bioreactor, a representative high-yield TAUT/CHO cell line (T10) showed >80% viability for more than 1 month and a 47% increase in medium MAb concentration. In T10 cells, the upregulation of TNF-α mRNA (an apoptosis marker) and the accumulation of ammonia late in the culture period were suppressed. Moreover, if an excess of taurine was added, T10 cells efficiently consumed glutamine but not other amino acids, so T10 cells may have gained a glutamine transporter-like function. Because a considerable amount of metabolic energy is derived from glutamine, this active glutamine consumption in T10 cells might be a reason for the improved cell viability and MAb concentration. These results demonstrate that forcing the overexpression of TAUT in CHO cells can enhance cell culture performance and increase MAb titer.

Tumor necrosis factor-induced nuclear factor kappaB activation is impaired in focal adhesion kinase-deficient fibroblasts.

Focal adhesion kinase (FAK) is widely involved in important cellular functions such as proliferation, migration, and survival, although its roles in immune and inflammatory responses have yet to be explored. We demonstrate a critical role for FAK in the tumor necrosis factor (TNF)-induced activation of nuclear factor (NF)-kappaB, using FAK-deficient (FAK-/-) embryonic fibroblasts. Interestingly, TNF-induced interleukin (IL)-6 production was nearly abolished in FAK-/- fibroblasts, whereas a normal level of production was obtained in FAK+/- or FAK+/+ fibroblasts. FAK deficiency did not affect the three types of mitogen-activated protein kinases, ERK, JNK, and p38. Similarly, TNF-induced activation of activator protein 1 or NF-IL-6 was not impaired in FAK-/- cells. Of note, TNF-induced NF-kappaB DNA binding activity and activation of IkappaB kinases (IKKs) were markedly impaired in FAK-/- cells, whereas the expression of TNF receptor I or other signaling molecules such as receptor-interacting protein (RIP), tumor necrosis factor receptor-associated factor 2 (TRAF2), IKKalpha, IKKbeta, and IKKgamma was unchanged. Also, TNF-induced association of FAK with RIP and subsequent association of RIP with TRAF2 were not observed, resulting in a failure of RIP to recruit the IKK complex in FAK-/- cells. The reintroduction of wild type FAK into FAK-/- cells restored the interaction of RIP with TRAF2 and the IKK complex and allowed recovery of NF-kappaB activation and subsequent IL-6 production. Thus, we propose a novel role for FAK in the NF-kappaB activation pathway leading to the production of cytokines.