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Background: With greater awareness and increased screening, cancers are increasingly being diagnosed at stage I. Women with these small node-negative tumours have excellent survival prospects after surgery, but many women, especially those with triple-negative and human epidermal growth factor receptor (HER)-2-positive tumours, still receive adjuvant systemic treatments to reduce the recurrence risk., Aims: We review the outcomes of women diagnosed with stage I (T1N0M0) tumours in our unit and examine the effect of systemic chemotherapy with/without targeted therapy on recurrence patterns and survival outcomes., Results: We reviewed 643 women diagnosed with T1N0M0 disease over a 10-year period. Five-year recurrence-free survival (RFS) was 96.6% and the 10-year RFS was 95.5%. Recurrence occurred in 4.7% of the women and was limited to locoregional sites in two-thirds of the instances. Systemic recurrences developed in 12 women, all of whom had ER-positive/HER2-negative disease. The mode of surgery emerged as the only independent predictor of recurrence. Recurrence was highest in women treated with wide local excision (WLE) alone ( p < 0.05), but not in those who had received breast radiation after WLE ( p = 0.112). Systemic chemotherapy, with or without anti-HER2 therapy, was discussed with 334 women, of whom 50.6% received the treatment; these women were more often younger and had triple-negative or HER2-positive tumours ( p < 0.001). Women who received chemotherapy showed a non-significant tendency to develop locoregional recurrence ( p = 0.104), but the number of systemic recurrences were similar to those documented in women who had not received chemotherapy. Chemotherapy and/or targeted treatment was not observed to have a significant effect on 5-year recurrence-free survival ( p = 0.444)., Conclusions: Stage I cancers have excellent survival outcomes. An optimal local surgical treatment is important and we did not find chemotherapy and/or targeted therapy to produce any significant differences in survival.

Background: Microalgae have emerged as sustainable alternatives to fossil fuels and high-value petrochemicals. Despite the commercial potential of microalgae, their low biomass productivity is a significant limiting factor for large-scale production. In the photoautotrophic cultivation of microalgae, achievable cell density levels depend on the light transmittance of the production system, which can significantly decrease the photosynthetic rate and biomass production. In contrast, the mixotrophic cultivation of microalgae using heterotrophic carbon sources enables high-density cultivation, which significantly enhances biomass productivity. The identification of optimal production conditions is crucial for improving biomass productivity; however, it is typically time- and resource-consuming. To overcome this problem, high-throughput screening (HTS) system presents a practical approach to maximize biomass and lipid production and enhance the industrial applicability of microalgae., Results: In this study, we proposed a two-step HTS assay that allows effective screening of heterotrophic conditions compatible with new microalgal isolates. To confirm the effectiveness of the HTS assay, three microalgal isolates with distinctive morphological and genetic traits were selected. Suitable cultivation conditions, including various heterotrophic carbon sources, substrate concentrations, and temperatures, were investigated using a two-step HTS assay. The optimized conditions were validated at the flask scale, which confirmed a significant enhancement in the biomass and lipid productivity of each isolate. Moreover, the two-step HTS assay notably enhanced economic and temporal efficiency compared to conventional flask-based optimization., Conclusions: These results suggest that our two-step HTS assay is an efficient strategy for investigating and optimizing microalgal culture conditions to maximize biomass and lipid productivity. This approach has the potential to enhance the industrial applicability of microalgae and facilitate the seamless transition from laboratory to field applications., (© 2024. The Author(s).)

Monodisperse nanoparticles of biodegradable polyhydroxyalkanoates (PHAs) polymers, copolymers of 3-hydroxybutyrate (3HB) and 4-hydroxybutyrate (4HB), are synthesized using a membrane-assisted emulsion encapsulation and evaporation process for biomedical resorbable adhesives. The precise control over the diameter of these PHA particles, ranging from 100 nm to 8 μm, is achieved by adjusting the diameter of emulsion or the PHA concentration. Mechanical properties of the particles can be tailored based on the 3HB to 4HB ratio and molecular weight, primarily influenced by the level of crystallinity. These monodisperse PHA particles in solution serve as adhesives for hydrogel systems, specifically those based on poly(N, N-dimethylacrylamide) (PDMA). Semi-crystalline PHA nanoparticles exhibit stronger adhesion energy than their amorphous counterparts. Due to their self-adhesiveness, adhesion energy increases even when those PHA nanoparticles form multilayers between hydrogels. Furthermore, as they degrade and are resorbed into the body, the PHA nanoparticles demonstrate efficacy in in vivo wound closure, underscoring their considerable impact on biomedical applications., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gi-Ra Yi reports financial support was provided by CJ CheilJedang Corp. Gi-Ra Yi has patent pending to POSTECH, CJ Cheiljedang Corp. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Microalgae are potential sustainable resources for the production of value-added chemicals that can be used as biofuels, pharmaceuticals, and nutritional supplements. Arachidonic acid (ARA), a omega-6 fatty acid, plays a crucial role in infant development and immune response, and can be used in cosmetics and pharmaceuticals. Demand for industrial-scale ARA production is continuously increasing because of its broad applicability. To address this demand, there has been a significant shift towards microorganism-based ARA production. To accelerate large-scale ARA production, it is crucial to select suitable strains and establish optimal culture conditions., Results: Here, we isolated a novel microalga Lobosphaera incisa CFRC-1, a valuable strain that holds promise as a feedstock for ARA production. Optimal cultivation conditions were investigated using a high-throughput screening method to enhance ARA production in this novel strain. Out of 71 candidates, four organic carbon substrates were identified that could be utilized by L. incisa CFRC-1. Through flask-scale verification, fructose was confirmed as the optimal organic carbon substrate for promoting microalgal growth, total lipid accumulation, and ARA production. Subsequently, we investigated appropriate substrate concentration and cultivation temperature, confirming that the optimal conditions were 30 g L - 1 of fructose and 27 ℃ of temperature. Under these optimized conditions, biomass and ARA production reached 13.05 ± 0.40 g L - 1 and 97.98 ± 7.33 mg L - 1 , respectively, representing 9.6-fold and 5.3-fold increases compared to the conditions before optimization conditions. These results achieved the highest biomass and ARA production in flask-scale cultivation, indicating that our approach effectively improved both production titer and productivity., Conclusions: This study presents a novel microalgae and optimized conditions for enhancing biomass and ARA production, suggesting that this approach is a practical way to accelerate the production of valuable microalgae-based chemicals. These findings provide a basis for large-scale production of ARA-utilizing microalgae for industrial applications., (© 2024. The Author(s).)

Post-operative radiotherapy for post-menopausal women with early breast cancer and N1 disease is controversial. Although locoregional control is improved, overall survival (OS) benefit is unclear. The clinical benefit of post-operative irradiation in this group of patients over 10 years was reviewed. We aimed to evaluate the OS, disease-free survival (DFS), and factors affecting OS and DFS. A retrospective review of 191 post-menopausal women with early breast cancer and N1 disease from 2004 to 2011 was performed. Demographics, post-operative histology, adjuvant treatment, OS, and DFS were evaluated. Post-operative radiation was given to 95 of 191 women (49.7%). Younger age at diagnosis ( p < 0.001), a greater number of involved nodes ( p = 0.004), lymphovascular invasion (LVI), and a higher tumor grade ( p = 0.001) were more likely in women who received post-operative radiation. Nodal radiation did not improve 10-year DFS ( p = 0.084) or OS ( p = 0.203). Post-operative nodal radiation was associated with significant improvement in 10-year OS in women who received only hormonal therapy ( p = 0.047) and no other systemic therapy. Women with unfavorable risk factors were more likely to receive post-operative radiation, likely due to a perceived higher risk of recurrence. Nodal radiation did not significantly improve 10-year DFS or OS in early breast cancer patients with N1 disease, and the benefit was not clearly demonstrated. However, in those who were on hormonal therapy, radiotherapy was beneficial in improving overall survival.

The AIM2 inflammasome is an innate immune system component that defends against cytosolic bacteria and DNA viruses, but its aberrant activation can lead to the progression of various inflammatory diseases, including psoriasis. However, there have been few reports of specific inhibitors of AIM2 inflammasome activation. In this study, we aimed to investigate the inhibitory activity of ethanolic extracts of seeds of Cornus officinalis (CO), a herb and food plant used in traditional medicine, on AIM2-inflammasome activation. We found that CO inhibited the release of IL-1β induced by dsDNA in both BMDMs and HaCaT cells, but that it showed no effect on the release of IL-1β induced by NLRP3 inflammasome triggers, such as nigericin and silica, or the NLRC4 inflammasome trigger flagellin. Furthermore, we demonstrated that CO inhibited the cleavage of caspase-1, an inflammasome activation marker, and an upstream event, the translocation and speck formation of ASC. In addition, further experiments and mechanistic investigations revealed that CO can inhibit AIM2 speck formation induced by dsDNA in AIM2-overexpressing HEK293T cells. To verify the correlation in vivo, we investigated the efficacy of CO in an imiquimod (IMQ)-induced psoriasis model, which has reported associations with the AIM2 inflammasome. We found that topical application of CO alleviated psoriasis-like symptoms, such as erythema, scaling, and epidermal thickening, in a dose-dependent manner. Moreover, CO also significantly decreased IMQ-induced expression of AIM2 inflammasome components, including AIM2, ASC, and caspase-1, and led to the elevation of serum IL-17A. In conclusion, our results suggest that CO may be a valuable candidate for the discovery of AIM2 inhibitors and the regulation of AIM2-related diseases.

In the past, plastic microbeads (MBs) were added to personal healthcare products to improve the cleaning and exfoliating effects, but these have been withdrawn owing to their non-degradable nature and contribution to the pollution of marine environment, especially that caused by the adsorption of persistent organic pollutants (POPs) on MBs. Therefore, natural biodegradable alternatives are being developed, but these often do not exhibit sufficient performance to replace non-degradable MBs. In this study, poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P3HB-4HB), a biodegradable aliphatic polyester, was used to prepare MBs via melt-electrospraying. We carried out the rheological characterization of P3HB-4HB with respect to melting temperature, and the melt-electrospray process was optimized to prepare MBs having sizes similar to those of commercially available MBs. Furthermore, the adsorption properties of the P3HB-4HB MBs for POPs were investigated. Unlike commercial MBs, the P3HB-4HB MBs adsorbed significantly fewer contaminants owing to their smooth and regular surfaces. Finally, a cleansing product containing P3HB-4HB MBs was prepared to evaluate their cleaning ability, and we found that the MB-based product could remove dirt and contaminants that were not easily removed by water alone. Thus, the biodegradable P3HB-4HB MBs have great potential for use as sustainable additives for cosmetic products for skin exfoliation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Chronological age (CA) predicts health status but its impact on health varies with anthropometry, socioeconomic status (SES), and lifestyle behaviors. Biological age (BA) is, therefore, considered a more precise predictor of health status. We aimed to develop a BA prediction model from self-assessed risk factors and validate it as an indicator for predicting the risk of chronic disease. A total of 101,980 healthy participants from the Korean Genome and Epidemiology Study were included in this study. BA was computed based on body measurements, SES, lifestyle behaviors, and presence of comorbidities using elastic net regression analysis. The effects of BA on diabetes mellitus (DM), hypertension (HT), combination of DM and HT, and chronic kidney disease were analyzed using Cox proportional hazards regression. A younger BA was associated with a lower risk of DM (HR = 0.63, 95% CI: 0.55-0.72), hypertension (HR = 0.74, 95% CI: 0.68-0.81), and combination of DM and HT (HR = 0.65, 95% CI: 0.47-0.91). The largest risk of disease was seen in those with a BA higher than their CA. A consistent association was also observed within the 5-year follow-up. BA, therefore, is an effective tool for detecting high-risk groups and preventing further risk of chronic diseases through individual and population-level interventions.

Relational bullying in schools is one of the most frequent forms of violence and can have severe negative health impact, e.g. depression. Social exclusion is the most prominent form of relational bullying that can be operationalized experimentally. The present study used MR-based perfusion imaging (pCASL) to investigate the neural signatures of social exclusion and its relationship with individually different extent of previous bullying experience. Twenty-four teenagers reporting bullying experience at different extent were scanned during a virtual ball-tossing (Cyberball game). Our findings showed that social exclusion (relative to social inclusion) activated frontal brain areas: sub- and perigenual anterior cingulate cortex (sg/pgACC), left inferior frontal cortex (IFG), and dorsolateral prefrontal cortex. Positive relationship between exclusion-specific signal increase and individually different extents of prior bullying experience was for the first time observed in left IFG and sgACC. This suggests that more frequent prior experience has conditioned greater mentalizing and/or rumination, in order to cope with the situation. While this interpretation remains speculative, the present data show that the experience of being bullied partly sensitizes the neural substrate relevant for the processing of social exclusion., Competing Interests: The authors have declared that no competing interests exist.

Purpose: We investigated the association between isoflavone (ISF) intake and hereditary breast cancer (BC) risk, particularly by molecular subtype, in East-Asian BRCA1/2 mutation carriers and non-carriers at a high risk of hereditary breast cancer (i.e., family history of BC (FHBC) and early-onset BC [EOBC, age < 40 years])., Methods: The association between ISF intake and BC risk by molecular subtypes was assessed in 1709 participants (407 BRCA1/2 carriers, 585 FHBC non-carriers, 586 EOBC non-carriers, and 131 unaffected non-carriers) from the Korean Hereditary Breast Cancer Study using hazard ratios (HRs) and 95% confidence intervals (CIs) in weighted Cox regression models. Daily ISF intake was assessed using a validated food frequency questionnaire. We evaluated gene-environment interactions between BRCA1/2 mutation and ISF intake in 1604 BC cases by calculating the case-only odds ratios (CORs) and 95% CIs in logistic regression models., Results: ISF intake was inversely associated with luminal A BC risk in BRCA2 mutation carriers and FHBC non-carriers (HR = 0.14, 95% CI = 0.04-0.50 for high intake [ISF intake ≥ 15.50 mg/day]; HR = 0.27, 95% CI = 0.11-0.69 for high intake, respectively). We observed a reduced risk of triple negative BC (TNBC) in BRCA1 carriers and FHBC non-carriers (HR = 0.09, 95% CI = 0.02-0.40 for high intake; HR = 0.19, 95% CI = 0.05-0.69 for high intake, respectively). In the case-only design, an interaction between BRCA1 mutation carrier status and ISF intake emerged in TNBC patients (COR = 0.39, 95% CI = 0.16-0.95)., Conclusions: This study suggests that ISF intake is inversely associated with BC risk in women at high risk of hereditary BC and that the effect could differ by molecular subtypes.

The grounding of concepts in the sensorimotor brain systems is controversially discussed. Grounded cognition models propose that concepts are represented in modality-specific sensorimotor, but also emotional and introspective brain areas depending on specific experiences during concept acquisition. Accumulating evidence suggests that concrete concepts are closely linked to modality-specific systems, whereas the mere existence of abstract concepts seems to contradict grounded cognition approaches. Here, using functional magnetic resonance imaging, we adopted a theory-driven approach frequently used for investigating concrete concepts to the domain of abstract concepts: We compared brain activation to abstract concepts with a known motor versus visual feature content as determined by a previous property listing study. Carefully matched motor (e.g., fitness) and visual (e.g., beauty) abstract words were presented to 24 participants along with pseudowords while performing a lexical decision task. Furthermore, participants performed two localizer tasks by actually moving their hands (motor localizer) and by looking at real pictures (visual localizer). Processing of motor abstract words specifically activated frontal and parietal motor areas, whereas processing of visual abstract words specifically elicited higher activity in temporo-occipital visual areas, albeit at a more lenient statistical threshold. According to inclusive masking analyses, this differential activity pattern to motor and visual abstract concepts overlapped with brain activations observed during hand movements (pre- and postcentral gyrus) and object perception (fusiform and lingual gyrus). Thus, consistent with the grounded cognition framework, our results suggest that, similar to concrete concepts, abstract concepts related to action and vision are grounded in modality-specific brain systems typically engaged in actual perception and action depending on their conceptual feature content., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Grounded cognition approaches to conceptual representations postulate a close link between conceptual knowledge and the sensorimotor brain systems. The present fMRI study tested, whether a feature-specific representation of concepts, as previously demonstrated for nouns, can also be found for action- and sound-related verbs. Participants were presented with action- and soundrelated verbs along with pseudoverbs while performing a lexical decision task. Sound-related verbs activated auditory areas in the temporal cortex, whereas action-related verbs activated brain regions in the superior frontal gyrus and the cerebellum, albeit only at a more liberal threshold. This differential brain activation during conceptual verb processing partially overlapped with or was adjacent to brain regions activated during the functional localizers probing sound perception or action execution. Activity in brain areas involved in the processing of action information was parametrically modulated by ratings of action relevance. Comparisons of action- and sound-related verbs with pseudoverbs revealed activation for both verb categories in auditory and motor areas. In contrast to proposals of strong grounded cognition approaches, our study did not demonstrate a considerable overlap of activations for action- and sound-related verbs and for the corresponding functional localizer tasks. However, in line with weaker variants of grounded cognition theories, the differential activation pattern for action- and sound-related verbs was near corresponding sensorimotor brain regions depending on conceptual feature relevance. Possibly, action-sound coupling resulted in a mutual activation of the motor and the auditory system for both action- and sound-related verbs, thereby reducing the effect sizes for the differential contrasts., (Copyright: © 2019 University of Economics and Human Sciences in Warsaw.)

Background: Psychotherapeutic interventions share common factors, which might contribute to treatment success independent of the type of psychotherapy. Previous research on common factors of psychotherapy was mostly conducted in outpatients and covered the development of common factors throughout a therapy over months or years. However, the role of common factors for the psychotherapeutic treatment success in inpatients during their hospital stay has not been addressed so far. The present research therefore aimed to explore changes of the common factors within a short-term stay at the psychiatric hospital for inpatients with major depressive disorder (MDD) and their relation to treatment outcome. Method: We developed a standardized manualized individual cognitive-behavioral psychotherapy (SMiCBT) for depression. The SMiCBT treatment lasted 4 weeks with eight therapy sessions. Following each treatment session, patients and therapists separately completed the questionnaire of "Stundenbogen für die Allgemeine und Differentielle Einzel-Psychotherapie" (STEP) to assess common factors from the perspective of the patient and the therapist. Severity of depression was also measured by the German version of the "Beck Depression Inventory" (BDI-II) before and after the treatment (SMiCBT). We conducted multilevel analysis for the longitudinal data for each scale of the STEP. Results: We found an improvement in the severity of depressive symptoms across the treatment period according to BDI-II scores. Regarding the STEP scales, motivational clarification and problem-solving scores increased over the treatment period for both patient and therapist perspectives. This was not the case for the scale therapeutic relationship. Furthermore, baseline levels of motivational clarification and problem solving were related to the treatment response. Limitations: The results have to be interpreted with care because of the small sample with MDD and the lack of a control group for comparison of treatment outcome. Conclusion: Our data demonstrate that common factors improve within a short-term psychotherapy in inpatients with MDD. Most importantly, our research highlights the distinguished role of motivational clarification and problem solving for the improvement of depressive symptoms during short-term psychotherapy in inpatient settings.

In the current emerging trend of using human mesenchymal stromal cell (MSCs) for cell therapy, large quantities of cells are needed for clinical testing. Current methods of culturing cells, using tissue culture flasks or cell multilayer vessels, are proving to be ineffective in terms of cost, space and manpower. Therefore, alternatives such as large-scale industrialized production of MSCs in stirred tank bioreactors using microcarriers (MCs) are needed. Moreover, the development of biodegradable MCs for MSC expansion can streamline the bioprocess by eliminating the need for enzymatic cell harvesting and scaffold seeding for bone-healing therapies. Our previous studies described a process of making regulated density (1.06 g/cm 3 ) porous polycaprolactone biodegradable MCs Light Polycarprolactone (LPCL) (MCs), which were used for expanding MSCs from various sources in stirred suspension culture. Here, we use human early MSCs (heMSCs) expanded on LPCL MCs for evaluation of their osteogenic differentiation potential in vitro as well as their use in vivo calvarial defect treatment in a rat model. In summary, (i) in vitro data show that LPCL MCs can be used to efficiently expand heMSCs in stirred cultures while maintaining surface marker expression; (ii) LPCL MCs can be used as scaffolds for cell transfer for transplantation in vivo; (iii) 50% sub-confluency, mid-logarithmic phase, on LPCL MCs (50% confluent) exhibited higher secretion levels of six cytokines (interleukin [IL]-6, IL-8, Vascular endothelial growth factor (VEGF), Monocyte Chemoattractant Protein-1 (MCP-1), growth-regulated oncogene-α (GRO-α) and stromal cell-derived factor-1α (SDF-1α)) as compared with 100% confluent, stationary phase cultures (100% confluent); (iv) these 50% confluent cultures demonstrated better in vitro osteogenic differentiation capacity as compared with 100% confluent cultures (higher levels of calcium deposition and at earlier stage); the improved bone differentiation capacity of these 50% confluent cultures was also demonstrated at the molecular level by higher expression of early osteoblast genes Runt-related transcription factor 2 (RUNX2), Alkaline phosphatase (ALP), collagen type I, osterix and osteocalcin); and (v) in vivo implantation of biodegradable LPCL MCs covered with 50% heMSCs into rats with calvarial defect demonstrated significantly better bone formation as compared with heMSCs obtained from monolayer cultures (5.1 ± 1.6 mm 3 versus 1.3 ± 0.7 mm 3 ). Moreover, the LPCL MCs covered with 50% heMSCs supported better in vivo bone formation compared with 100% confluent culture (2.1 ± 1.3 mm 3 ). Taken together, our study highlights the potential of implanting 50% confluent MSCs propagated on LPCL MCs as optimal for bone regeneration. This methodology allows for the production of large numbers of MSCs in a three-dimensional (3D) stirred reactor, while supporting improved bone healing and eliminating the need for a 3D matrix support scaffold, as traditionally used in bone-healing treatments., (Copyright © 2019 International Society for Cell and Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Large numbers of human mesenchymal stromal cells (MSCs) used for a variety of applications in tissue engineering and cell therapy can be generated by scalable expansion in a bioreactor using microcarriers (MCs) systems. However, the enzymatic digestion process needed to detach cells from the growth surface can affect cell viability and potentially the potency and differentiation efficiency. Thus, the main aim of our study was to develop biocompatible and biodegradable MCs that can support high MSC yields while maintaining their differentiation capability and potency. After cell expansion, the cells that covered MCs can be directly implanted in vivo without the need for cell harvesting or use of scaffold. Poly-ε-caprolactone (PCL) is known as a biocompatible and biodegradable material. However, it cannot be used for generation of MCs because its high density (1.14 g/cm 3 ) would exclude its applicability for suspension MCs in stirred reactors. In this article, we describe expansion and potency of MSCs propagated on low-density (1.06 g/cm 3 ) porous PCL MCs coated with extracellular matrices (LPCLs) in suspended stirred reactors. Using these LPCLs, cell yields of about 4 × 10 4 cells/cm 2 and 7- to 10-fold increases were obtained using four different MSC lines (bone marrow, cord blood, fetal and Wharton's jelly). These yields were comparable with those obtained using non-degradable MCs (Cytodex 3) and higher than two-dimensional monolayer (MNL) cultures. A fed-batch process, which demonstrated faster cell expansion (4.5 × 10 4 cells/cm 2 in 5 days as compared with 7 days in batch culture) and about 70% reduction in growth media usage, was developed and scaled up from 100-mL spinner flask to 1-L controlled bioreactor. Surface marker expression, trilineage differentiation and clonogenic potential of the MSCs expanded on LPCL were not affected. Cytokine secretion kinetics, which occurred mostly during late logarithmic phase, was usually comparable with that obtained in Cytodex 3 cultures and higher than MNL cultures. In conclusion, biodegradable LPCL can be used to efficiently expand a variety of MSC lines in stirred scalable reactors in a cost-effective manner while maintaining surface markers expression, differentiation capability and high levels of cytokine secretion. This study is the first step in testing these cell-biodegradable porous MC aggregates for tissue engineering and cell therapy, such as bone and cartilage regeneration, or wound healing., (Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Morus bombycis Koidzumi (M. bombycis, Moraceae) has been used in Asian countries as a traditional medicine for the treatment of hypertension, diabetes, and inflammation-related disorders., Aim of Study: Although its anti-inflammatory actions have been partly documented, scientific evidence involving its molecular mechanisms related to inflammasome activation signaling pathways remains unknown., Materials and Methods: Lipopolysaccharide-stimulated RAW 264.7 cells and bone marrow-derived murine macrophages were used to study the in vitro effect of methanolic extract of M. bombycis (MB) on inflammatory responses. A monosodium urate crystal (MSU)-induced peritonitis murine model was used to study the in vivo effects., Results: MB attenuated the production of nitric oxide and interleukin-6, through the regulation of the interferon-β receptor signaling pathway. MB also inhibited IL-1β secretion via attenuation of NLRP3 inflammasome activation. Furthermore, MB inhibited MSU-induced peritonitis in the in vivo murine model., Conclusions: This study provides the key molecular mechanisms involved in the anti-inflammatory effects of M. bombycis, substantiating the traditional claims of its use in the treatment of inflammation-related disorders., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Evaluative priming by masked emotional stimuli that are not consciously perceived has been taken as evidence that affective stimulus evaluation can also occur unconsciously. However, as masked priming effects were small and frequently observed only for familiar primes that there also presented as visible targets in an evaluative decision task, priming was thought to reflect primarily response activation based on acquired S-R associations and not evaluative semantic stimulus analysis. The present study therefore assessed across three experiments boundary conditions for the emergence of masked evaluative priming effects with unfamiliar primes in an evaluative decision task and investigated the role of the frequency of target repetition on priming with pictorial and verbal stimuli. While familiar primes elicited robust priming effects in all conditions, priming effects by unfamiliar primes were reliably obtained for low repetition (pictures) or unrepeated targets (words), but not for targets repeated at a high frequency. This suggests that unfamiliar masked stimuli only elicit evaluative priming effects when the task set associated with the visible target involves evaluative semantic analysis and is not based on S-R triggered responding as for high repetition targets. The present results therefore converge with the growing body of evidence demonstrating attentional control influences on unconscious processing., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Recent evidence suggests an interaction between the ventral visual-perceptual and dorsal visuo-motor brain systems during the course of object recognition. However, the precise function of the dorsal stream for perception remains to be determined. The present study specified the functional contribution of the visuo-motor system to visual object recognition using functional magnetic resonance imaging and event-related potential (ERP) during action priming. Primes were movies showing hands performing an action with an object with the object being erased, followed by a manipulable target object, which either afforded a similar or a dissimilar action (congruent vs. incongruent condition). Participants had to recognize the target object within a picture-word matching task. Priming-related reductions of brain activity were found in frontal and parietal visuo-motor areas as well as in ventral regions including inferior and anterior temporal areas. Effective connectivity analyses suggested functional influences of parietal areas on anterior temporal areas. ERPs revealed priming-related source activity in visuo-motor regions at about 120 ms and later activity in the ventral stream at about 380 ms. Hence, rapidly initiated visuo-motor processes within the dorsal stream functionally contribute to visual object recognition in interaction with ventral stream processes dedicated to visual analysis and semantic integration., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Ethnopharmacological Relevance: Impatiens textori Miq. (I. textori, Balsaminaceae) is a traditional medicinal herb used for centuries to treat several inflammatory related skin infections and allergic disorders in Asian countries., Aim of the Study: In this study, we elucidated the effects of whole plant extracts of I. textori on inflammasome activation using in vitro and in vivo models., Materials and Methods: LPS-stimulated murine bone marrow macrophages were used to study the regulatory effect of I. textori extract (IT) on inflammasome activation. ATP, nigericin and MSU were used as danger-associated molecules to activate the NLRP3 inflammasome. An LPS-induced acute lung injury (ALI) mouse model was used to study the in vivo effect of IT on inflammasome activation., Results: IT treated at 25, 50, and 100μg/mL concentrations suppressed interleukin-1β secretion through the attenuation of NLRP3 inflammasome activation (p<0.001 at 100μg/mL) leading to the decreased amount of ASC oligomerization and caspase-1 maturation. For the in vivo model, IT inhibited the NLRP3 expression and cell recruitment at the lung tissue in the ALI mouse model., Conclusion: IT exhibited potent anti-inflammatory effects via the attenuation of NLRP3 inflammasome activation supporting the traditional claims and may provide a valuable therapeutic strategy in treating various inflammation-related disorders., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Antimicrobial peptides (AMPs), also called host defense peptides, particularly those with amphipathic helical structures, are emerging as target molecules for therapeutic development due to their immunomodulatory properties. Although the antimicrobial activity of AMPs is known to be exerted primarily by permeation of the bacterial membrane, the mechanism underlying its anti-inflammatory activity remains to be elucidated. We report potent anti-inflammatory activity of WALK11.3, an antimicrobial model peptide with an amphipathic helical conformation, in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. This peptide inhibited the expression of inflammatory mediators, including nitric oxide, COX-2, IL-1β, IL-6, INF-β, and TNF-α. Although WALK11.3 did not exert a major effect on all downstream signaling in the MyD88-dependent pathway, toll-like receptor 4 (TLR4)- mediated pro-inflammatory signals were markedly attenuated in the TRIF-dependent pathway due to inhibition of the phosphorylation of STAT1 by attenuation of IRF3 phosphorylation. WALK11.3 specifically inhibited the endocytosis of TLR4, which is essential for triggering TRIF-mediated signaling in macrophage cells. Hence, we suggest that specific interference with TLR4 endocytosis could be one of the major modes of the anti-inflammatory action of AMPs. Our designed WALK11 peptides, which possess both antimicrobial and anti-inflammatory activities, may be promising molecules for the development of therapies for infectious inflammation.

Emodin, an active constituent of oriental herbs, is widely used to treat allergy, inflammation, and other symptoms. This study provides the scientific basis for the anti-inflammasome effects of emodin on both in vitro and in vivo experimental models. Bone marrow-derived macrophages were used to study the effects of emodin on inflammasome activation by using inflammasome inducers such as ATP, nigericin, and silica crystals. The lipopolysaccharide (LPS)-induced endotoxin shock model was employed to study the effect of emodin on in vivo efficacy. Emodin treatment attenuated interleukin (IL)-1β secretion via the inhibition of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation induced by ATP, nigericin, and silica crystals. Further, emodin ameliorated the severity of NLRP3 inflammasome-mediated symptoms in LPS-induced endotoxin mouse models. This study is the first to reveal mechanism-based evidence, especially with respect to regulation of inflammasome activation, substantiating traditional claims of emodin in the treatment of inflammation-related disorders.

The BDNF Val66Met polymorphism has been linked to decreased synaptic plasticity involved in motor learning tasks. We investigated whether individual differences in this polymorphism may promote differences in neural activity during a two-alternative forced-choice motor performance. In two separate sessions, the BOLD signal from 22 right-handed healthy men was measured during button presses with the left and right index finger upon visual presentation of an arrow. 11 men were Val66Val carriers (ValVal group), the other 11 men carried either the Val66Met or the Met66Met polymorphism (Non-ValVal group). Reaction times, resting and active motor thresholds did not differ between ValVal and Non-ValVal groups. Compared to the ValVal group the Non-ValVal group showed significantly higher BOLD signals in the right SMA and motor cingulate cortex during motor performance. This difference was highly consistent for both hands and across all four sessions. Our finding suggests that this BDNF polymorphism may not only influence complex performance during motor learning but is already associated with activation differences during rather simple motor tasks. The higher BOLD signal observed in Non-ValVal subjects suggests the presence of cumulative effects of the polymorphism on the motor system, and may reflect compensatory functional activation mediating equal behavioral performance between groups.

Aim: To explore the feasibility of using SMS to conduct health surveys in patients with rheumatoid arthritis (RA)., Methods: Using a two-way SMS system, we conducted a baseline survey using a short and a long quality of life instrument, with two follow-up administrations of the short survey among patients with RA on follow-up at the Singapore General Hospital (SGH). Our outcome variables were survey response rate, question response time, proportion of replies following the format instructions, and survey administration cost., Results: Among 85 participants (of 99 eligible patients approached), the response rate was 67% for the long survey, 80% for the short survey at baseline, and 74% and 70% at the first and second follow-ups, respectively. Survey response rate varied with the employment status of respondents. Approximately 78% of all replies followed the format instructions. All these replies were received within the stipulated 24-h timeline and half of them were received within 29 min. Response time for the other 22% of replies that did not follow the format instructions was much longer. The average administration cost per survey was S$0.34 (equivalent of US$0.26)., Conclusions: Two-way SMS is a promising tool to conduct short health surveys. Evidence for implementing long surveys over SMS is still weak. The post survey interviews with survey participants suggested that sequential delivery of survey questions coupled with SMS reminders in the interim, tailoring survey questions to individual health conditions, and providing feedback on individual survey results can potentially improve the response rate of such surveys., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Research in psychotherapy has shown that the frequency of use of specific classes of words (such as terms with emotional valence) in descriptions of scenes of affective relevance is a possible indicator of psychological affective functioning. Using functional magnetic resonance imaging (MRI), we investigated the neural correlates of these linguistic markers in narrative texts depicting core aspects of emotional experience in human interaction, and their modulation by individual differences in the propensity to use these markers. Emotional words activated both lateral and medial aspects of the prefrontal cortex, as in previous studies of instructed emotion regulation and in consistence with recruitment of effortful control processes. However, individual differences in the spontaneous use of emotional terms in characterizing the stimulus material were prevalently associated with modulation of the signal in the perigenual cortex, in the retrosplenial cortex and precuneus, and the anterior insula/ventrolateral prefrontal cortex. Modulation of signal by the presence of these textual markers or individual differences mostly involved areas deactivated by the main task, thus further differentiating neural correlates of these appraisal styles from those associated with effortful control. These findings are discussed in the context of reports in the literature of modulations of deactivations, which suggest their importance in orienting attention and generation of response in the presence of emotional information. These findings suggest that deactivations may play a functional role in emotional appraisal and may contribute to characterizing different appraisal styles.

Modality-specific models of conceptual memory propose close links between concepts and the sensory-motor systems. Neuroimaging studies found, in different subject groups, that action-related and sound-related concepts activated different parts of posterior middle temporal gyrus (pMTG), suggesting a modality-specific representation of conceptual features. However, as these different parts of pMTG are close to each other, it is possible that the observed anatomical difference is merely related to interindividual variability. In the present functional magnetic resonance imaging study, we now investigated within the same participant group a possible conceptual feature-specific organization in pMTG. Participants performed lexical decisions on sound-related (e.g., telephone) and action-related (hammer) words. Sound words elicited higher activity in anterior pMTG adjacent to auditory association cortex, but action-related words did so in posterior pMTG close to motion sensitive areas. These results confirm distinct conceptual representations of sound and action in pMTG, just adjacent to the respective modality-specific cortices., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Cognitive control can be adapted flexibly according to the conflict level in a given situation. In the Eriksen flanker task, interference evoked by flankers is larger in conditions with a higher, rather than a lower proportion of compatible trials. Such compatibility ratio effects also occur for stimuli presented at two spatial locations suggesting that different cognitive control settings can be simultaneously maintained. However, the conditions and the neural correlates of this flexible adaptation of cognitive control are only poorly understood. In the present study, we further elucidated the mechanisms underlying the simultaneous maintenance of two cognitive control settings. In behavioral experiments, stimuli were presented centrally above and below fixation and hence processed by both hemispheres or lateralized to stimulate hemispheres differentially. The different compatibility ratio at two stimulus locations had a differential influence on the flanker effect in both experiments. In an fMRI experiment, blocks with an identical compatibility ratio at two central spatial locations elicited stronger activity in a network of prefrontal and parietal brain areas, which are known to be involved in conflict resolution and cognitive control, as compared with blocks with a different compatibility ratio at the same spatial locations. This demonstrates that the simultaneous maintenance of two conflicting control settings vs. one single setting does not recruit additional neural circuits suggesting the involvement of one single cognitive control system. Instead a crosstalk between multiple control settings renders adaptation of cognitive control more efficient when only one uniform rather than two different control settings has to be simultaneously maintained., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Perception and action are classically thought to be supported by functionally and neuroanatomically distinct mechanisms. However, recent behavioral studies using an action priming paradigm challenged this view and showed that action representations can facilitate object recognition. This study determined whether action representations influence object recognition during early visual processing stages, that is, within the first 150 msec. To this end, the time course of brain activation underlying such action priming effects was examined by recording ERPs. Subjects were sequentially presented with two manipulable objects (e.g., tools), which had to be named. In the congruent condition, both objects afforded similar actions, whereas dissimilar actions were afforded in the incongruent condition. In order to test the influence of the prime modality on action priming, the first object (prime) was presented either as picture or as word. We found an ERP effect of action priming over the central scalp as early as 100 msec after target onset for pictorial, but not for verbal primes. A later action priming effect on the N400 ERP component known to index semantic integration processes was obtained for both picture and word primes. The early effect was generated in a fronto-parietal motor network, whereas the late effect reflected activity in anterior temporal areas. The present results indicate that action priming influences object recognition through both fast and slow pathways: Action priming affects rapid visuomotor processes only when elicited by pictorial prime stimuli. However, it also modulates comparably slow conceptual integration processes independent of the prime modality.

Professional musicians constitute a model par excellence for understanding experience-dependent plasticity in the human brain, particularly in the auditory domain. Their intensive sensorimotor experience with musical instruments has been shown to entail plastic brain alterations in cortical perceptual and motor maps. It remains an important question whether this neuroplasticity might extend beyond basic perceptual and motor functions and even shape higher-level conceptualizations by which we conceive our physical and social world. Here we show using functional magnetic resonance imaging (fMRI) that conceptual processing of visually presented musical instruments activates auditory association cortex encompassing right posterior superior temporal gyrus, as well as adjacent areas in the superior temporal sulcus and the upper part of middle temporal gyrus (pSTG/MTG) only in musicians, but not in musical laypersons. These areas in and adjacent to auditory association cortex were not only recruited by conceptual processing of musical instruments during visual object recognition, but also by auditory perception of real sounds. Hence, the unique intensive experience of musicians with musical instruments establishes a link between auditory perceptual and conceptual brain systems. Experience-driven neuroplasticity in musicians is thus not confined to alterations of perceptual and motor maps, but even leads to the establishment of higher-level semantic representations for musical instruments in and adjacent to auditory association cortex. These findings highlight the eminent importance of sensory and motor experience for acquiring rich concepts., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The cytochrome P450 2D6 (CYP2D6) is a genetically polymorphic enzyme involved in the metabolism of several psychoactive drugs. Beside its expression in the liver, CYP2D6 is highly expressed in several regions of the brain, such as the hippocampus, thalamus, hypothalamus and the cortex, but its function in the brain is not well understood. The CYP2D6 enzyme may also have a physiological role due to its involvement in neurotransmitter biotransformation. In this study, CYP2D6 genotyping was performed in N=188 healthy individuals and compared with brain perfusion levels at rest, which may reflect an ongoing biological process regulating the reactivity of the individual to emotional stimuli and the detection of signals evoking fear. Relative to N=42 matched extensive metabolizers, N=14 poor metabolizers were associated with 15% higher perfusion levels in the thalamus (P=0.03 and 0.003). Effects were also present in the whole (N=188) sample divided into metabolizer groups, or finely graded into seven CYP2D6 activity levels. A weaker effect was observed in the right hippocampus (P=0.05). An exploratory analysis, extended to the whole brain, suggested the involvement of CYP2D6 in regions associated with alertness or serotonergic function. These findings support the hypothesis of a functional role of CYP2D6 in the brain.

Objective: This study investigated the mental health of former 'comfort women' who serviced the Japanese Imperial Military during the Second World War., Method: We evaluated 26 former comfort women's life histories, cognitive functioning, DSM-IV diagnosis of posttraumatic stress disorder (PTSD), depression, paranoid state, anger, and Rorschach test results, and compared the data with those of 24 healthy women., Results: Cognitive functioning was not significantly different between former comfort women and the comparison group. All 26 former comfort women had undergone traumatic experiences such as sexual slavery and had suffered PTSD symptoms at least once in their lives. Of the 26, 8 (30.8%) were diagnosed as having PTSD, as opposed to none in the comparison group. The women's PTSD symptoms were characterized by avoidance behavior, intrusive and distressing recollections, and anger. There were no significant differences in depression or paranoid state between the two groups, but former comfort women had impairments in anger control. Former comfort women with PTSD were more depressed. On the Rorschach test, former comfort women revealed characteristic responses related not only to sex and morbidity but also to anger and violence., Limitations: The small number of subjects might not represent all former comfort women. Some data collected by self report might limit the objectivity of the results., Conclusions: The results suggest that former comfort women are still suffering from traumatic memories, symptoms of PTSD, including avoidant behavior, and anger control impairment, even 60 years after the end of the war.

Even in the presence of negative information, healthy human beings display an optimistic tendency when thinking of past success and future chances, giving a positive bias to everyday's cognition. The tendency to actively select positive thoughts suggests the existence of a mechanism to exclude negative content, raising the issue of its dependence on mechanisms like those of effortful control. Using perfusion imaging, we examined how brain activations differed according to whether participants were left to prefer positive thoughts spontaneously, or followed an explicit instruction to the same effect, finding a widespread dissociation of brain perfusion patterns. Under spontaneous processing of emotional material, recruitment of areas associated with effortful attention, such as the dorsolateral prefrontal cortex, was reduced relative to instructed avoidance of negative material (F(1,58) = 26.24, p = 0.047, corrected). Under spontaneous avoidance perfusion increments were observed in several areas that were deactivated by the task, including the perigenual medial prefrontal cortex. Furthermore, individual differences in executive capacity were not associated with positive bias. These findings suggest that spontaneous positive cognitive emotion regulation in health may result from processes that, while actively suppressing emotionally salient information, differ from those associated with effortful and directed control.

Background: Images of perfusion estimates obtained with the continuous arterial spin labelling technique are characterized by variation between single acquisitions. Little is known about the spatial determinants of this variation during the acquisition process and their impact on voxel-by-voxel estimates of effects., Results: We show here that the spatial patterns of covariance between voxels arising during the acquisition of these images uncover distinct mechanisms through which this variance arises: through variation in global perfusion levels; through the action of large vessels and other, less well characterized, large anatomical structures; and through the effect of noisy areas such as the edges of the brain., Conclusions: Knowledge of these covariance patterns is important to experimenters for a correct interpretation of findings, especially for studies where relatively few acquisitions are made.

Background: The serotonin transporter length repeat polymorphism (5-HTTLPR) in the promoter region of the serotonin transporter gene (SLC6A4) has been associated in healthy subjects with changes in basal perfusion levels in the limbic system and ventral prefrontal areas, regions involved in the pathophysiology of depression and anxiety, suggesting the existence of a neurobiological trait predisposing to these disorders. We reassess the findings of an increased baseline perfusion in the amygdala and ventral prefrontal areas in healthy carriers of the risk genotype in a much larger sample than in previous studies., Methods: A cohort of 183 healthy European individuals underwent perfusion imaging with continuous arterial spin-labeling (CASL) while resting quietly in the scanner for 8 minutes. Participants were genotyped to assess the occurrence of the short allele and the Lg and La variants of the long repeat., Results: No association between the 5-HTTLPR polymorphism and baseline brain perfusion was detected in the regions of interest or elsewhere in the brain. In the amygdala, variability in baseline perfusion was explained in large part by global cerebral flow levels (between 50% and 55%), in minor part by sex (between 4% and 5%), but not by genotype (less than .5%). Power analyses showed that the study was of sufficient size to be informative., Conclusions: The findings did not confirm the existence of a biological marker of the effect of 5-HTTLPR polymorphism in the amygdala or in the orbitofrontal cortex., (2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Simple baseline studies correlate average perfusion levels measured at rest with individual variables, or contrast subject groups as in case-control studies. In this methodological work, we summarize some formal properties of the design of these studies, and investigate the sources of variance that characterize data acquired with the arterial spin labeling technique, with the purpose of alerting users to the main sources of variation that determine background variance and affect the power of statistical tests. This design typology is characterized by two variance components: between acquisitions and between subjects. We show that variation between acquisitions is affected by the presence of large vessels and venous sinuses, with potential adverse effects especially in the temporal and insular regions, and provide maps of the number of acquisitions or subjects required to reach the desired estimate precision. Furthermore, we show that the largest source of variation between subjects is captured by global perfusion levels, and can in principle be removed by adjusting the data. Significance levels, however, are not always only improved by the adjustment procedure; we provide an example in the correlation with age, and attempt to explain the consequences of the adjustment with the help of a principal component analysis of the data. We also show the existence of variation between subjects in the perfusion in the territory of the posterior cerebral artery and in hemispheric asymmetry.

Early studies of rest cerebral metabolism and perfusion reported no association with intellectual capacity. We revisit this issue using a larger sample (N=146) and a continuous arterial spin labeling technique to measure perfusion, and working memory capacity as a measure of intellectual capacity. In the cortex, working memory capacity correlated diffusely and negatively with perfusion. This negative association was more marked in the prefrontal and temporal cortex of the left hemisphere. However, there were also weak positive correlations in the auditory areas, accompanied by analogous correlations in all other areas associated with sensory modalities, with a preference for right lateralization. These findings are discussed in terms of the cortical and vascular organization of the brain.

Traditionally, concepts are conceived as abstract mental entities distinct from perceptual or motor brain systems. However, recent results let assume modality-specific representations of concepts. The ultimate test for grounding concepts in perception requires the fulfillment of the following four markers: conceptual processing during (1) an implicit task should activate (2) a perceptual region (3) rapidly and (4) selectively. Here, we show using functional magnetic resonance imaging and recordings of event-related potentials, that acoustic conceptual features recruit auditory brain areas even when implicitly presented through visual words. Fulfilling the four markers, the findings of our study unequivocally link the auditory and conceptual brain systems: recognition of words denoting objects, for which acoustic features are highly relevant (e.g.,"telephone"), ignited cell assemblies in posterior superior and middle temporal gyri (pSTG/MTG) within 150 ms that were also activated by sound perception. Importantly, activity within a cluster of pSTG/MTG increased selectively as a function of acoustic, but not of visual and action-related feature relevance. The implicitness of the conceptual task, the selective modulation of left pSTG/MTG activity by acoustic feature relevance, the early onset of this activity at 150 ms and its anatomical overlap with perceptual sound processing are four markers for a modality-specific representation of auditory conceptual features in left pSTG/MTG. Our results therefore provide the first direct evidence for a link between perceptual and conceptual acoustic processing. They demonstrate that access to concepts involves a partial reinstatement of brain activity during the perception of objects.

Traditionally, concepts are assumed to be situational invariant mental knowledge entities (conceptual stability), which are represented in a unitary brain system distinct from sensory and motor areas (amodality). However, accumulating evidence suggests that concepts are embodied in perception and action in that their conceptual features are stored within modality-specific semantic maps in the sensory and motor cortex. Nonetheless, the first traditional assumption of conceptual stability largely remains unquestioned. Here, we tested the notion of flexible concepts using functional magnetic resonance imaging and event-related potentials (ERPs) during the verification of two attribute types (visual, action-related) for words denoting artifactual and natural objects. Functional imaging predominantly revealed crossover interactions between category and attribute type in visual, motor, and motion-related brain areas, indicating that access to conceptual knowledge is strongly modulated by attribute type: Activity in these areas was highest when nondominant conceptual attributes had to be verified. ERPs indicated that these category-attribute interactions emerged as early as 116 msec after stimulus onset, suggesting that they reflect rapid access to conceptual features rather than postconceptual processing. Our results suggest that concepts are situational-dependent mental entities. They are composed of semantic features which are flexibly recruited from distributed, yet localized, semantic maps in modality-specific brain regions depending on contextual constraints.

Concepts are composed of features related to different sensory and motor modalities such as vision, sound, and action. It is a matter of controversy whether conceptual features are represented in sensory-motor areas reflecting the specific learning experience during acquisition. In order to address this issue, we assessed the plasticity of conceptual representations by training human participants with novel objects under different training conditions. These objects were assigned to categories such that for one class of categories, the overall shape was diagnostic for category membership, whereas for the other class, a detail feature affording a particular action was diagnostic. During training, participants were asked to either make an action pantomime toward the detail feature of the novel object or point to it. In a categorization task at test, we assessed the neural correlates of the acquired conceptual representations by measuring electrical brain activity. Here, we show that the same object is differentially processed depending on the sensory-motor interactions during knowledge acquisition. Only in the pantomime group did we find early activation in frontal motor regions and later activation in occipito-parietal visual-motor regions. In the pointing training group, these effects were absent. These results show that action information contributes to conceptual processing depending on the specific learning experience. In line with modality-specific theories of conceptual memory, our study suggests that conceptual representations are established by the learning-based formation of cell assemblies in sensory-motor areas.

It is debated whether category-related brain activation reflects a modality-specific (e.g., visual, functional representation systems) or a domain-specific (e.g., natural vs. artifactual categories) semantic memory organization. The present event-related potentials (ERPs) study is aimed at elucidating the nature of semantic representations of objects from natural (e.g., animal) and artifactual (e.g., tool) categories. Within a repetition priming paradigm, we tested the assumption that modality-specific semantic systems are differentially involved in representing artifacts and natural kinds by probing either visual or functional knowledge in a test task. In the exposure phase, subjects performed a classification task on object names for artifacts and natural objects. In the test phase, these previously presented (old) names were presented together with new names, and subjects had to perform either a visual (shape) or a functional (use) judgment. As in previous ERP studies, words from natural categories were associated with a more positive potential at occipito-parietal electrodes than words from artifactual categories. This effect was only obtained during the visual judgment task. This category-related ERP effect was diminished for words that had been previously presented. In the functional judgment task, category-related ERP effects were not obtained at all, probably due to the heterogeneity of the probed features. The observed interaction between task, category and repetition provides direct evidence that visual features play a more important role for the representations of natural compared to artifactual categories. Our data are therefore compatible with the notion of modality-specific semantic systems.

A multiplex PCR was designed for the differential diagnosis of the two parasite species by targeting the 18S rRNA gene with a set of primer combinations, amplifying DNA fragments of 1451-bp and 833-bp for P. falciparum and P. vivax, respectively. The sensitivity of this PCR test was high, as minimal as 0.1 parasite per one microliter of blood sample and a minimum of four copies of the target gene could be detected. For the diagnosis of mixed infection of two Plasmodium spp., there were no apparent competition or cross-reaction between the majority and minority Plasmodium species. The multiplex PCR was evaluated on 210 clinical samples and 60 normal controls. The PCR test yielded highly concordant results with microscopic examination, with the only one exception of a mixed (P. falciparum plus P. vivax) infection case, which was diagnosed as a single infection of P. falciparum by microscopy. We propose that the multiplex PCR is a sensitive, specific, and rapid tool that can serve as a useful differential diagnostic tool for detecting P. falciparum and P. vivax.

The present study was designed to investigate polymorphism in Duffy binding protein (DBP) gene of Plasmodium vivax isolates of Korea. Thirty samples were obtained from P. vivax patients in Yonchon-gun, Kyonggi-do in 1998. The PCR products of the samples were subjected to sequencing and hybridization analyses of the regions II and IV of P. vivax DBP gene. Two genotypes, SK-1 and SK-2, were identified on the basis of amino acid substitution and deletion. The genotype of 10 isolates was SK-1 and that of 20 isolates was SK-2. Most of the predicted amino acids in the region II of DBP gene were conserved between the Korean isolates and Belem strain except for 4-5 amino acid substitutions. In the region IV of DBP, a 6-bp insert that was shown in the Sal-1 allele type was found in SK-1, and a 27-bp insert that was shown in the Papua New Guinea allele type was found in SK-2. In conclusion, the present findings suggest that two genotypes of P. vivax coexist in the endemic area of Korea.