Reciprocal Actions Research Articles

Interleukin-1 receptor antagonist inhibits angiogenesis in gastric cancer

BackgroundInterleukin-1 alpha (IL-1α) plays an important role in tumorigenesis and angiogenesis of gastric cancer. The interleukin-1 receptor antagonist (IL-1RA) inhibits IL-1 selectively and specifically through IL-1R type I (IL-1RI). However, the underlying mechanism by which IL-1RA modulates the interactions of tumor cells and their micro-environment is poorly understood. We have evaluated the role of IL-1RA in the metastatic process as well as the mutual or reciprocal actions between gastric cancer cells and stromal cells.Materials and methodsThe expressions of IL-1α, vascular endothelial growth factor (VEGF), and IL-1RI mRNA were determined by reverse transcriptase-PCR. The regulatory effect of IL-1RA on the secretion of VEGF in human gastric cancer cells and human umbilical vein endothelial cells (HUVECs) was detected by enzyme-linked immunosorbent assay. The effect of IL-1RA on metastatic potential was evaluated using proliferation, invasion, and angiogenesis assays, respectively, including in vitro co-culture system models consisting of tumor cells and stromal cells that were used to detect invasion and angiogenesis.ResultsInterleukin-1α mRNA was detected in the higher liver metastatic gastric cell line MKN45. IL-1α protein was expressed in MKN45 cells and in HUVECs. VEGF mRNA and protein were detected in the three gastric cancer cell lines (MKN4, NUGC-4, and AGS). Levels of VEGF secreted by gastric cancer cells and HUVECs appeared to be reduced through the action of IL-1RA via IL-1RI in a dose-dependent manner (P < 0.01). IL-1RA significantly inhibited the proliferation and migration of HUVECs (P < 0.01) and tube formation by HUVECs (P < 0.01), both in a dose-dependent manner. Compared with HUVECs grown without cancer cells (control) or with NUGC-4 cells, tube formation by HUVECs was significantly enhanced by co-culture with MKN45 cells (P < 0.01). The enhanced tube formation in the presence of MKN45 cells was inhibited by the addition of IL-1RA (P < 0.01).ConclusionsThe IL-1RA downregulated the metastatic potential of gastric cancer through blockage of the IL-1α/VEGF signaling pathways. IL-1RA has the potential to play a role in the treatment of gastric cancer.

Inhibition of cholesterol biosynthesis through RNF145-dependent ubiquitination of SCAP.

Cholesterol homeostasis is maintained through concerted action of the SREBPs and LXRs. Here, we report that RNF145, a previously uncharacterized ER membrane ubiquitin ligase, participates in crosstalk between these critical signaling pathways. RNF145 expression is induced in response to LXR activation and high-cholesterol diet feeding. Transduction of RNF145 into mouse liver inhibits the expression of genes involved in cholesterol biosynthesis and reduces plasma cholesterol levels. Conversely, acute suppression of RNF145 via shRNA-mediated knockdown, or chronic inactivation of RNF145 by genetic deletion, potentiates the expression of cholesterol biosynthetic genes and increases cholesterol levels both in liver and plasma. Mechanistic studies show that RNF145 triggers ubiquitination of SCAP on lysine residues within a cytoplasmic loop essential for COPII binding, potentially inhibiting its transport to Golgi and subsequent processing of SREBP-2. These findings define an additional mechanism linking hepatic sterol levels to the reciprocal actions of the SREBP-2 and LXR pathways.

Disrupting mitochondrial Ca2+ homeostasis causes tumor-selective TRAIL sensitization through mitochondrial network abnormalities

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has emerged as a promising anticancer agent with high tumor-selective cytotoxicity. The congenital and acquired resistance of some cancer types including malignant melanoma and osteosarcoma impede the current TRAIL therapy of these cancers. Since fine tuning of the intracellular Ca2+ level is essential for cell function and survival, Ca2+ dynamics could be a promising target for cancer treatment. Recently, we demonstrated that mitochondrial Ca2+ removal increased TRAIL efficacy toward malignant melanoma and osteosarcoma cells. Here we report that mitochondrial Ca2+ overload leads to tumor-selective sensitization to TRAIL cytotoxicity. Treatment with the mitochondrial Na+/Ca2+ exchanger inhibitor CGP-37157 and oxidative phosphorylation inhibitor antimycinA and FCCP resulted in a rapid and persistent mitochondrial Ca2+ rise. These agents also increased TRAIL sensitivity in a tumor-selective manner with a switching from apoptosis to a nonapoptotic cell death. Moreover, we found that mitochondrial Ca2+ overload led to increased mitochondrial fragmentation, while mitochondrial Ca2+ removal resulted in mitochondrial hyperfusion. Regardless of their reciprocal actions on the mitochondrial dynamics, both interventions commonly exacerbated TRAIL-induced mitochondrial network abnormalities. These results expand our previous study and suggest that an appropriate level of mitochondrial Ca2+ is essential for maintaining the mitochondrial dynamics and the survival of these cells. Thus, disturbing mitochondrial Ca2+ homeostasis may serve as a promising approach to overcome the TRAIL resistance of these cancers withminimally compromising the tumor-selectivity.

Pharmacological treatment of motor symptoms in Parkinson's diseases

Since the 1960s many substance classes have been introduced for treatment of idiopathic Parkinson's disease. The most important and effective medication is levodopa (L-dopa) always in combination with a decarboxylase inhibitor. In addition, dopamine agonists, monoamine oxidase B (MAO-B) inhibitors, catechol-o-methyltransferase (COMT) inhibitors, N‑methyl-D-aspartate (NMDA) antagonists and very rarely anticholinergics are administered depending on the motor symptoms, age and a multitude of other factors. Fortunately, within the substance classes there are various preparations, which also have different effects. In order that the advantages of the individual medications can be exploited and undesired effects and interactions can be avoided, one must come to terms with the complex data and the pharmacology of the medication. In addition important aspects are interactions and reciprocal actions. In the foreseeable future, different substance classes are to be expected.

On establishing I think as a final particle in interactions: Some comparisons with sentence-final particles in Japanese

This paper explores the function of I think in utterance-final position and attempts to establish its status as a final particle (FP). The pragmatic functions of I think are compared to those of sentence-final particles (SFPs) in Japanese, and the final particle-ness of I think is examined in terms of its placement in the so-called ‘right periphery.’ The findings suggest that the basic function of I think is to present an appraisal indicating interpersonal concern and attentiveness to the interactional context. In essence, I think presents the utterance as part of a set of reciprocal actions and implicitly solicits a responsive action by the recipient. Despite differences in intensity, these intrinsic functions of I think are comparable to those suggested for the Japanese SFPs yo and ne. The study concludes that final I think has specific functions as a FP distinct from those of its initial counterpart, indicating different types and/or levels of (inter)subjectivity.

Investigating the human Calcineurin Interaction Network using the πɸLxVP SLiM.

Ser/thr phosphorylation is the primary reversible covalent modification of proteins in eukaryotes. As a consequence, it is the reciprocal actions of kinases and phosphatases that act as key molecular switches to fine tune cellular events. It has been well documented that ~400 human ser/thr kinases engage substrates via consensus phosphosite sequences. Strikingly, we know comparatively little about the mechanism by which ~40 human protein ser/thr phosphatases (PSPs) dephosphorylate ~15000 different substrates with high specificity. The identification of substrates of the essential PSP calcineurin (CN) has been exceptionally challenging and only a small fraction has been biochemically confirmed. It is now emerging that CN binds regulators and substrates via two short linear motifs (SLiMs), the well-studied PxIxIT SLiM and the LxVP SLiM, which remains controversial at the molecular level. Here we describe the crystal structure of CN in complex with its substrate NFATc1 and show that the LxVP SLiM is correctly defined as πɸLxVP. Bioinformatics studies using the πɸLxVP SLiM resulted in the identification of 567 potential CN substrates; a small subset was experimentally confirmed. This combined structural-bioinformatics approach provides a powerful method for dissecting the CN interaction network and for elucidating the role of CN in human health and disease.

Flows driven by libration, precession, and tides in planetary cores

A thorough description of challenges and recent progress in the understanding of flows in planetary molten cores is provided, with particular attention to flow driven by mechanical forcing due to the tugging of one celestial body on another. This case is particularly relevant for the understanding of the reciprocal actions in the Moon/Earth system.

Caring and connectedness in the context of domestic worker employment in South Africa

This study investigated workplace relational connectedness qualities in terms of domestic worker employment in a South African setting. Twenty black female domestic workers were recruited through purposive respondent-driven self-sampling. Participants ranged in age from 27 to 59 years. Semi-structured in-depth interviews were used to generate the data. An interpretative phenomenological approach was used to foreground the thematic data analysis. Caring and connectedness emerged as the main theme that characterised participants’ positive employment relationships. Identified sub-themes related to participants’ experience of their employment context, work engagement and treatment, psychosocial well-being and communication. The findings are consistent with the broaden-and-build theory which proposes a positive behavioural cycle which results from reciprocal actions.

Reciprocating (More) Specifically to You: The Role of Benefactor's Identifiability on Direct and Upstream Reciprocity

AbstractResearch suggests that benefiting from someone's voluntary, intentional, costly effort encourages reciprocal prosocial behavior, as well as promoting upstream reciprocity, that is, increases reciprocal actions by the recipient for the benefit of an unrelated third party. The current study examines the role of the identifiability of the benefactor in determining the extent to which people engage in direct and upstream reciprocity. Results of three studies reveal that while an identified benefactor tends to engender greater direct reciprocal reactions than an unidentified one, this strong reaction toward the identified benefactor does not hold to the same extent when upstream reciprocity is considered (regardless of identification of the third party). On the other hand, when the benefactor is unidentified, levels of direct and upstream reciprocity remain similar. Moderated‐mediation analysis suggests that ethical commitment associated with the universal norm of reciprocity explains the decrease in prosociality between reactions toward the benefactor himself or herself and toward a third party under the identified condition. Copyright © 2016 John Wiley &amp; Sons, Ltd.

Social interaction patterns according to stocking density and time post-mixing in group-housed gestating sows

Housing systems should enable animals to interact socially while minimising aggression. This study investigated whether social interaction patterns in groups of indoor-housed gestating sows are affected by stocking density (‘SD’), by varying the number of sows per pen, and day after mixing. Unacquainted sows were grouped within 5 days of insemination at 1.45 (High; ‘H-SD’), 2.0 (Moderate; ‘M-SD’) or 2.9 m2 per sow (Low; ‘L-SD’) by placing 20, 14 or 10 sows per pen. Five pens per treatment were represented, and within each pen, 10 focal sows were observed. Social behaviours between focal sows were analysed continuously for 15 min after drop-feeding the day after mixing (Day 2) and 1 week later (Day 9), and plasma cortisol and progesterone concentrations analysed on Days 2 and 26. Overall, 587 interactions were observed, with 59% being short one reciprocal actions. Sows used more physical aggression at H-SD on Day 2 such as bites (vs M-SD and L-SD: both P &lt; 0.01), head knocks and pushes (vs L-SD: P = 0.01; vs M-SD: P = 0.06), whereas social interactions at lower SD were more frequent (L-SD vs H-SD: P = 0.004; L-SD vs M-SD: P = 0.02) and contained presumably neutral social behaviours such as nose contacts (L-SD vs H-SD: P = 0.06; M-SD vs H-SD: P = 0.07), or non-physical agonistic behaviours such as threats (L-SD vs H-SD: P = 0.07). A first-order Markov transitional analysis revealed positive feedback loops for bites and knocks or pushes at higher SD on Day 2 (all P &lt; 0.05). Cortisol concentration decreased as SD decreased (L-SD vs H-SD: P &lt; 0.001; L-SD vs M-SD: P = 0.02; M-SD vs H-SD: P = 0.07). Hence, interactions were more aggressive and less frequent at higher SD at Day 2 post-mixing, but differences vanished at Day 9. Valuable information can be gained from analysing the type of social behaviours and behavioural sequences, in addition to overall aggression frequency.

Abstract A20: Tumorigenicity of Ewing sarcoma is critically dependent on the trithorax proteins MLL and menin

Abstract Ewing sarcoma is driven by the oncogenic fusion protein, EWS-FLI1, and arises via de-regulation of developmental transcriptional programs. Control of normal developmental transcription programs is governed by epigenetic regulation which, in the case of HOX programs, is dependent on coordinated and reciprocal actions of polycomb (PcG) and trithorax (TrxG) proteins. We recently reported that in Ewing sarcoma posterior HOX genes, in particular HOXD13, are abnormally over-expressed and that the promoters of these genes are marked with the TrxG-dependent activating histone modification, H3K4me3. H3K4me3 is deposited by the MLL methyltransferase, a key enzyme that is frequently mutated in leukemia, largely as a result of chromosomal translocations that induce the creation of oncogenic MLL fusion-proteins. In leukemia, MLL fusion-proteins cooperate with wild-type MLL and the scaffolding protein menin to induce malignant transformation via deregulation of HOXA genes. The purpose of this study was to test the hypothesis that MLL and menin contribute to tumorigenesis and to posterior HOX gene deregulation in Ewing sarcoma. Gene and protein expression were determined by microarray, qRT-PCR, western blot and immunohistochemistry. Loss of function was achieved by lentiviral shRNAs and by exposing cells to MI-503, a small molecule inhibitor of menin-MLL protein-protein interactions. Changes in gene and protein expression after MI-503 treatment were assessed by qRT-PCR and western blot. Chromatin immunoprecipitation (ChIP) was used to assess binding of MLL and menin at gene promoters. Our results confirm that MLL, menin and HOXD13 are all highly expressed by Ewing sarcoma tumors and cell lines relative to non-malignant tissues and stem cells, and loss of function studies implicate each as a tumor promoting oncogene. Specifically, knockdown of MLL, menin or HOXD13 resulted in reduced cell proliferation, increased death and/or reduced tumorigenic capacity, as determined by anchorage-independent growth in soft agar and subcutaneous tumor formation in vivo. At a molecular level, knockdown of MLL and menin led to reduced expression of HOXD13, implicating these proteins as key mediators of HOXD13 over-expression. Exposure of Ewing sarcoma cells to MI-503 inhibited proliferation and colony formation in soft agar, and resulted in reduced expression of HOXD13 as well as other posterior HOX genes. In contrast, MI-NC, a control compound with similar structure that lacks affinity for the menin-MLL interaction had no effect on cell growth, viability or HOX gene expression. Significantly, MI-503-treated cells also showed a marked reduction in EWS-FLI1 and wild-type EWSR1 expression, both of which are regulated by the EWSR1 promoter, and of EZH2, a well-established oncogene in Ewing sarcoma. ChIP studies of the EWSR1 and EZH2 promoters demonstrated reduced binding of MLL and menin in MI-503-treated cells. These data demonstrate a key role for MLL and menin in Ewing sarcoma pathogenesis and directly implicate the TrxG complex in regulation of EWS-FLI1, thus highlighting a novel opportunity for therapeutic intervention. Citation Format: Laurie K. Svoboda, Natashay Bailey, Melanie Krook, Raelene Van Noord, Ashley Harris, Rajiv M. Patel, Dafydd Thomas, Tomek Cierpicki, Jolanta Grembecka, Elizabeth R. Lawlor. Tumorigenicity of Ewing sarcoma is critically dependent on the trithorax proteins MLL and menin. [abstract]. In: Proceedings of the AACR Special Conference: Developmental Biology and Cancer; Nov 30-Dec 3, 2015; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(4_Suppl):Abstract nr A20.

Status quo effects in fairness games: reciprocal responses to acts of commission versus acts of omission

Both the law and culture distinguish between acts of commission that overturn the status quo and acts of omission that uphold it. This distinction is of central importance when it comes to reciprocal actions. A stylized fact of everyday life is that acts of commission elicit stronger reciprocal responses than do acts of omission. We report experiments that directly test whether this stylized fact characterizes behavior in controlled experiments. We compare reciprocal responses to both types of acts in experiments using binary, extensive form games. Across three experiments, we examine the robustness of our results to different ways in which the status quo can be induced in experiments. The data show a clear difference between effects of acts of commission and omission by first movers on reciprocal responses by second movers.

Neither cortisol nor brain-derived neurotrophic factor is associated with serotonin transporter in bipolar disorder

Converging evidence indicates the hypothalamus–pituitary–adrenal axis and serotonergic neurons exert reciprocal modulatory actions. Likewise, brain-derived neurotrophic factor (BDNF) has been implicated as a growth and differentiation factor in the development of serotonergic neurons. The aim of this study was to examine the interaction of cortisol and BDNF on serotonin transporter (SERT) in bipolar disorder (BD). Twenty-eight BD and 28 age- and gender-matched healthy controls (HCs) were recruited. 123I-ADAM with single-photon emission computed tomography (SPECT) was applied for measurement of SERT availability in the brain, which included the midbrain, thalamus, putamen and caudate. Ten milliliters of venous blood was withdrawn, when the subject underwent SPECT, for the measurement of the plasma concentration of cortisol and BDNF. SERT availability was significantly decreased in the midbrain and caudate of BD compared with HCs, whereas plasma concentration of cortisol and BDNF did not show a significant difference. The linear mixed-effect model revealed that there was a significant interaction of group and cortisol on SERT availability of the midbrain, but not BDNF. Linear regression analyses by groups revealed that cortisol was associated with SERT availability in the midbrain in the HCs, but not in BD. Considering previous studies, which showed a significant association of cortisol with SERT availability in the HCs and major depressive disorder (MDD), our result replicated a similar finding in HCs. However, the negative finding of the association of cortisol and SERT availability in BD, which was different from MDD, suggests a different role for cortisol in the pathophysiology of mood disorder.

Abstract 490: The Trithorax proteins menin and MLL promote Ewing sarcoma tumorigenicity

Abstract Normal development is governed by covalent modifications to chromatin that are mediated by the reciprocal actions of Polycomb group (PcG) and Trithorax (TrxG) proteins, which promote gene repression and activation, respectively. We recently reported that HOX genes, key developmental transcription factors that are regulated by PcG and TrxG during embryogenesis, are abnormally expressed in Ewing sarcoma (ES). In particular, we found that the posterior HOXD genes, including HOXD13, are markedly overexpressed, and that the promoters of these genes are aberrantly marked with the TrxG-dependent histone mark, H3K4me3. The TrxG proteins MLL and menin cooperate to drive HOX gene expression and promote tumorigenesis in leukemia. We therefore hypothesized that MLL and menin might also contribute to ES pathogenesis. Gene and protein expression were determined by microarray, q-RT-PCR and western blot of ES cell lines and tumors. Lentiviral shRNA constructs were used to knock down HOXD13, menin and MLL. Proliferation, survival, and tumorigenicity of genetically modified cells were assessed in vitro and in vivo. Inhibition of TrxG function was achieved by exposing cells to MI-503, a small molecule inhibitor of menin-MLL interactions. Our results confirm that menin, MLL and HOXD13 are all highly expressed by ES relative to non-malignant tissues and stem cells. Moreover, loss of function studies implicate each as a tumor promoting oncogene. Specifically, knockdown of HOXD13, menin or MLL inhibited cell proliferation and cell death was also induced by loss of either MLL or HOXD13. Colony formation in soft agar was likewise inhibited by MLL and HOXD13 knockdown and tumor formation in vivo was significantly delayed in ES cells with reduced expression of HOXD13. Importantly, knockdown of MLL led to reduced expression of HOXD13 further implicating MLL as a key mediator of HOXD13 over-expression in ES and supporting the hypothesis that, like MLL-fusion-dependent leukemias, HOX deregulation and tumorigenicity in ES are dependent on the TrxG complex. To further test this hypothesis we exposed ES cells to MI-503, an inhibitor of menin-MLL protein-protein interaction that disrupts the TrxG complex. Exposure of ES cells to MI-503 resulted in a dose-dependent inhibition of cell proliferation and marked inhibition of colony formation in soft agar. In contrast, MI-NC, a control compound with similar structure that lacks affinity for the menin-MLL interaction had no effect on ES cell growth or viability. Together these data for the first time demonstrate a key role for menin and MLL in ES pathogenesis and highlight a novel opportunity for therapeutic intervention in these aggressive tumors. Citation Format: Laurie K. Svoboda, Cassondra Cramer, Ashley Harris, Natashay Bailey, Tomek Cierpicki, Jolanta Grembecka, Elizabeth Lawlor. The Trithorax proteins menin and MLL promote Ewing sarcoma tumorigenicity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 490. doi:10.1158/1538-7445.AM2015-490

Surface Emg Traditional And Wavelet Transform Parameters Applied To Monitor Changes After Exercise-Induced Muscle Damage

Investigations have demonstrated that exercise-induced muscle damage can inhibit muscle performance post-exercise. However, to overcome the non-stationary condition and low sensitivity to muscle fatigue of the traditional parameters, some new techniques have been proposed to monitor muscle fatigue more accurately. PURPOSE: To correlate the traditional and stationary wavelet transform parameters which can explain peak torque output during maximal isometric contractions before and after exercise-induced muscle damage. METHODS: Thirteen resistance trained males (age: 23.9 ±5.2 years; body mass: 79.2 ±9.9 kg; height: 176.1 ±6.3 cm) volunteered to take part in this study. Subjects performed 4 sets of 10 unilateral maximal elbow flexion concentric/eccentric reciprocal actions with their dominant arm. They were seated in a chair with their arms draped over a “preacher curl bench.” All exercise was performed on a Biodex System 3 isokinetic dynamometer at 120°s-1 with one minute rest between sets. Maximal voluntary isometric contraction of the elbow flexors was measured at 90° of flexion for 3 seconds. Isometric peak torque (PT) and the surface electromyography (sEMG) of the biceps brachii were collected at baseline and immediately post exercise. Traditional parameters of amplitude (RMS) and frequency (MdF) of the sEMG signal were calculated with a specific routine written in Matlab (v 6.5, Mathworks, Natick, MA). The signal was also decomposed into five detail coefficients (D1 to D5) using the discrete wavelet transform (mother wavelet Daubechies 5). A Pearson correlation was used to associate the decrease in PT (ΔPT) with variations in RMS, MdF and energy of the wavelets details. RESULTS: Pearson’s r values were positive correlated between PT and all sEMG parameters. However, there was only a strong relationship between ΔPT and D3 (r=0.79). CONCLUSION: The energy of D3 from discrete wavelet transform used in the present study was more sensitive in assessing changes in muscle performance following exercise-induced muscle damage.

Corticospinal and reciprocal inhibition actions on human soleus motoneuron activity during standing and walking.

Reciprocal Ia inhibition constitutes a key segmental neuronal pathway for coordination of antagonist muscles. In this study, we investigated the soleus H-reflex and reciprocal inhibition exerted from flexor group Ia afferents on soleus motoneurons during standing and walking in 15 healthy subjects following transcranial magnetic stimulation (TMS). The effects of separate TMS or deep peroneal nerve (DPN) stimulation and the effects of combined (TMS + DPN) stimuli on the soleus H-reflex were assessed during standing and at mid- and late stance phases of walking. Subthreshold TMS induced short-latency facilitation on the soleus H-reflex that was present during standing and at midstance but not at late stance of walking. Reciprocal inhibition was increased during standing and at late stance but not at the midstance phase of walking. The effects of combined TMS and DPN stimuli on the soleus H-reflex significantly changed between tasks, resulting in an extra facilitation of the soleus H-reflex during standing and not during walking. Our findings indicate that corticospinal inputs and Ia inhibitory interneurons interact at the spinal level in a task-dependent manner, and that corticospinal modulation of reciprocal Ia inhibition is stronger during standing than during walking.

Transitory or Lingering Impact? The Legacies of the Cheonan Incident in Northeast Asia

What changes has the Cheonan incident brought about in the Northeast Asian region? How and to what extent have those changes shifted as time goes by? I find that the Cheonan sinking has played a key role in deepening the ideological chasm in South Korea between conservatives and progressives. It has also become a serious obstacle to the improvement of South Korea-North Korea relations, and has been the catalyst for the emergence of a Cold War-like rivalry between the US-South Korea-Japan and the China-North Korea-Russia blocs. However, relations among neigh-boring countries in Northeast Asia have shifted over time, including significant improvement in China-Republic of Korea relations and worsening of relations between China and North Korea and South Korea and Japan. KEYWORDS: Cheonan incident, ideological divide, South Korean politics, inter-Korean relations, Northeast Asian security relations.ON MARCH 26, 2010, THE REPUBLIC OF KOREA (ROK OR SOUTH Korea) navy corvette PCC-722 Cheonan sank while conducting a patrol mission in the Yellow Sea just south of the Northern Limit Line near Baekryeong Island. As a result, forty-six out of 104 crew members were killed while fifty-eight were rescued. Following an investigation, a Joint Civilian-Military Investigation Group (JIG) consisting of experts from the United States, the United Kingdom, Australia, Sweden, and South Korea, announced on May 20 that the Cheonan had been sunk by a North Korean torpedo attack. What changes has the Cheonan incident brought about in the Northeast Asia region? How and to what extent have those changes shifted over time?The JIG's official report, instead of leading to a consensus view among South Koreans, sparked a debate over the cause of the incident. The already deep ideological chasm between con- servatives and progressives in South Korean society worsened. The sinking of the Cheonan also further undermined interKorean relations and served as the catalyst for the emergence of a Cold War-like rivalry between the US-ROK-Japan and the China-North Korea-Russia blocs. Along with these changes in regional security dynamics, the tragic incident also exerted significant influence on interstate relations among neighboring countries in Northeast Asia. In the short run, the Cheonan sinking weakened China-ROK, US-DPRK (Democratic People's Republic of Korea, or North Korea), and US-China relations, whereas it helped strengthen China-DPRK, US-ROK, US-Japan, and ROK-Japan relations. Further shifts have occurred since the incident as China-ROK relations have significantly improved while China-DPRK and ROK-Japan relations have notably worsened.In this article, I first examine the widening ideological gap between conservatives and progressives in South Korea after the sinking of the navy ship by exploring the hotly contested points of the JIG's report. I then look into the impact of the Cheonan incident on Northeast Asian security relations and how and to what extent the changes produced by the incident have shifted over time.The Ideological Divide in South KoreaA Catalyst for Deepening MistrustIdeological disputes between conservatives and progressives in South Korea are hardly new. Since the end of the Korean War, the two camps have mainly clashed over policies toward the DPRK and the security role of the United States. Conservatives give top priority to fostering a close partnership with the United States and maintaining vigilance against the threat from North Korea. Progressives, however, radically oppose that narrative, seeing the North more as a kin nation with which to be reconciled and the United States as a disruptive interloper (Chae and Kim 2008, 77).This ideological divide became more evident after progressive President Kim Dae-jung (1998-2002) launched an engagement policy toward North Korea, called the Sunshine Policy. Conservative politicians, intellectuals, and media strongly opposed the Kim government's initiatives, criticizing him for not demanding reciprocal actions by the DPRK. …

Fibroblasts and myofibroblasts in wound healing.

(Myo)fibroblasts are key players for maintaining skin homeostasis and for orchestrating physiological tissue repair. (Myo)fibroblasts are embedded in a sophisticated extracellular matrix (ECM) that they secrete, and a complex and interactive dialogue exists between (myo)fibroblasts and their microenvironment. In addition to the secretion of the ECM, (myo)fibroblasts, by secreting matrix metalloproteinases and tissue inhibitors of metalloproteinases, are able to remodel this ECM. (Myo)fibroblasts and their microenvironment form an evolving network during tissue repair, with reciprocal actions leading to cell differentiation, proliferation, quiescence, or apoptosis, and actions on growth factor bioavailability by binding, sequestration, and activation. In addition, the (myo)fibroblast phenotype is regulated by mechanical stresses to which they are subjected and thus by mechanical signaling. In pathological situations (excessive scarring or fibrosis), or during aging, this dialogue between the (myo)fibroblasts and their microenvironment may be altered or disrupted, leading to repair defects or to injuries with damaged and/or cosmetic skin alterations such as wrinkle development. The intimate dialogue between the (myo)fibroblasts and their microenvironment therefore represents a fascinating domain that must be better understood in order not only to characterize new therapeutic targets and drugs able to prevent or treat pathological developments but also to interfere with skin alterations observed during normal aging or premature aging induced by a deleterious environment.

Efeitos crônicos do exercício resistido com contrações recíprocas no desempenho funcional e proprioceptivo de indivíduos jovens: ensaio controlado aleatório

Studies have suggested that benefits from resistance exercise (RE) using antagonist muscle pre-activation could be transferred to functional activities. However, chronic studies using pre-activation through reciprocal actions in neuromuscular performance and functional activities are scarce. The aim of this study is to compare the effects of 12 RE sessions using reciprocal muscle actions and a traditional mode on functional and proprioceptive performance of young individuals. Forty eight young subjects were randomized into two groups: 1) reciprocal training (RT, 3 sets; 10 repetitions; knee flexion immediately followed by knee extension), 2) traditional training (TRA, 3 sets. 10 repetitions; knee extension). Pre and post evaluations were characterized by balance tests, hop tests (HT) and 8 shape circuit (RC8). ANOVA 2X2 of mixed model was applied to analyze differences between pre and post-training conditions and between groups. For overall and anterior-posterior balance, no significant differences were found between RT and TRA (p>0.05). Similarly, no post-training differences were found. The medial lateral balance in the dominant limb showed no significant differences in post-training for both groups (p = 0.94), but the non-dominant limb showed significant differences between groups (p<0.01). In HT, significant post-training increases were found within groups (p<0.01), but no differences were found between them (p=0.90). RC8 was different between groups (p=0.03), indicating better post-training running time for TRA. Resistance exercise caused transfers to balance and functional performance, and training with reciprocal muscle actions showed better rates for HT and medial lateral knee balance

Mathematical interaction shaped by communication, epistemological constraints and enactivism

On the surface, mathematical interaction often appears as an immediately transparent event that could be directly understood by careful observation. Theoretical considerations, however, clearly show that mathematical speaking and conversation in teaching–learning situations are highly complex social structures comprising many preconditions. Communication does not generate direct understanding and the object of communication—mathematics—is, as knowledge of abstract relations, not directly accessible. The learning agents—the teacher and students in the mathematics classroom—have to cope with these difficulties in a way of reciprocal actions between social communication and individual consciousness.