Search

In this letter, we propose the Interactive Text2Pickup (IT2P) network for human-robot collaboration that enables an effective interaction with a human user despite the ambiguity in user's commands. We focus on the task where a robot is expected to pick up an object instructed by a human, and to interact with the human when the given instruction is vague. The proposed network understands the command from the human user and estimates the position of the desired object first. To handle the inherent ambiguity in human language commands, a suitable question which can resolve the ambiguity is generated. The user's answer to the question is combined with the initial command and given back to the network, resulting in more accurate estimation. The experiment results show that given unambiguous commands, the proposed method can estimate the position of the requested object with an accuracy of 98.49% based on the test dataset. Given ambiguous language commands, we show that the accuracy of the pick up task increases by 1.94 times after incorporating the information obtained from the interaction.

This article assesses the mechanisms whereby first-person narratives featuring stigmatized immigrants improve outgroup attitudes and encourage intergroup contact among prejudiced individuals. We rely on a 2 (imagined contact vs. control) × 2 (similar vs. dissimilar message protagonist) experiment on a systematic sample of native British adults. Results show that encouraging imagined contact prior to reading a short testimonial featuring an immigrant protagonist who is similar to the recipients in terms of social identity enhances identification with the protagonist, thereby improving outgroup attitudes and encouraging intergroup contact, and especially strongly among those who are prejudiced toward immigrants (i.e., high on modern racism). Theoretical and practical implications of the findings for the work on imagined contact, narrative persuasion, and identification, as well as for public communication campaigns, are discussed. Research work developed thanks to the financial sup-port granted by Spanish Ministry of Economy andCompetitiveness to the project entitled “Narrative toolsto reduce prejudice. Effects of similarity, imaginedcontact, empathy and narrative voice” (reference:CSO2015-67611-P).

SummaryCell proliferation and terminal differentiation are intimately coordinated during metazoan development. Here, we adapt a cyclin-dependent kinase (CDK) sensor to uncouple these cell cycle-associated events live inC. elegansand zebrafish. The CDK sensor consists of a fluorescently tagged CDK substrate that steadily translocates from the nucleus to the cytoplasm in response to increasing CDK activity and consequent sensor phosphorylation. We show that the CDK sensor can distinguish cycling cells in G1 from terminally differentiated cells in G0, revealing a commitment point and a cryptic stochasticity in an otherwise invariantC. eleganscell lineage. We also derive a predictive model of future proliferation behavior inC. elegansand zebrafish based on a snapshot of CDK activity in newly born cells. Thus, we introduce a live-cell imaging tool to facilitatein vivostudies of cell cycle control in a wide-range of developmental contexts.

Based on two experiments, this paper advances the concept of social presence as a novel mechanism through which narrative perspective (first- versus third-person) exerts persuasive effects on attitudes toward outgroup policies and behavioral intentions to help outgroup members. Study 1 (N = 503) shows that the first-person perspective, compared to the third- person perspective, increases social presence of the protagonist, but not identification with the protagonist, when the story depicted an outgroup character. This increase in social presence mediates the effect of narrative perspective on support for outgroup policies. Study 2 (N = 410) further suggests that social presence mediates the effect of narrative perspective regardless of the protagonist’s group membership (in-group versus out-group). Furthermore, this project evaluates the role of social presence in light of other, often-studied processes such as identification and transportation. These findings advance the theorizing and research in narrative research and in media psychology more broadly. Ministry of Education (MOE) Accepted version This work was partially supported by the Singapore Ministry of Education Academic Research Fund Tier 1 Grant.

Recepteur d'Origine Nantais (RON) expression is known to induce oncogenic properties including tumor cell growth, survival, motility, angiogenesis and chemoresistance. In the present study, we evaluated whether RON affects chemosensitivity and oncogenic behavior of colorectal cancer cells and investigated its prognostic value in colorectal cancer. To evaluate the impact of RON on chemosensitivity and tumor cell behavior, we treated colorectal cancer cells with small interfering RNAs specific to RON. This was followed by flow cytometric analyses and migration, Matrigel invasion and endothelial tube formation assays. The expression of RON was investigated by immunohistochemistry in colorectal cancer tissues. TUNEL assay and immunohistochemical staining for CD34 and D2-40 were deployed to determine apoptosis, angiogenesis and lymphangiogenesis. RON knockdown enhanced 5-fluorouracil (FU)-induced apoptosis by upregulating the activities of caspases and expression of proapoptotic genes. Moreover, it enhanced 5-FU-induced cell cycle arrest by decreasing the expression of cyclins and cyclin‑dependent kinases and inducing that of p21. Furthermore, RON knockdown augmented the 5-FU-induced inhibition of invasion and migration of colorectal cancer cells. The β-catenin signaling cascade was blocked by RON knockdown upon 5-FU treatment. RON knockdown also decreased endothelial tube formation and expression of VEGF-A and HIF-1α and increased angiostatin expression. Furthermore, it inhibited lymphatic endothelial cell tube formation and the expression of VEGF-C and COX-2. RON expression was observed to be associated with age, tumor size, lymphovascular and perineural invasion, tumor stage, lymph node and distant metastasis, and poor survival rate. The mean microvessel density value of RON-positive tumors was significantly higher than that of RON-negative ones. These results indicate that RON is associated with tumor progression by inhibiting chemosensitivity and enhancing angiogenesis in colorectal cancer.

Prospero homeobox 1 (PROX1) functions as a tumor suppressor gene or an oncogene in various cancer types. However, the distinct function of PROX1 in gastric cancer is unclear. We determined whether PROX1 affected the oncogenic behavior of gastric cancer cells and investigated its prognostic value in patients with gastric cancer. A small interfering RNA against PROX1 was used to silence PROX1 expression in gastric cancer cell lines AGS and SNU638. Expression of PROX1 in gastric cancer tissues was investigated by performing immunohistochemistry. Apoptosis, proliferation, angiogenesis, and lymphangiogenesis were determined by performing the TUNEL assay and immunohistochemical staining for Ki-67, CD34, and D2-40. PROX1 knockdown induced apoptosis by activating cleaved caspase-3, caspase-7, caspase-9, and poly(ADP-ribose) polymerase, and by decreasing the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL. PROX1 knockdown also suppressed tumor cell proliferation. In addition, PROX1 knockdown decreased lymphatic endothelial cell invasion and tube formation and the expression of vascular endothelial growth factor (VEGF)-C and -D and cyclooxygenase (COX)-2. However, PROX1 knockdown only decreased umbilical vein endothelial cell invasion, not tube formation. The mean Ki-67 labeling index and lymphatic vessel density value of PROX1-positive tumors were significantly higher than those of PROX1-negative tumors. However, no significant difference was observed between PROX1 expression and apoptotic index or microvessel density. PROX1 expression was significantly associated with age, cell differentiation, lymph node metastasis, cancer stage, and poor survival. These results indicate that PROX1 mediates the progression of gastric cancer by inducing tumor cell proliferation and lymphangiogenesis.

This article seeks to offer a broad examination of the historical trajectory of Neo-Confucian thought in the Chosŏn Dynasty of the nineteenth century. In so doing, the article aspires to go beyond the pre-established view of equating Neo-Confucianism with the conservative wijŏng ch’ŏksa (“upholding orthodoxy, rejecting heterodoxy”) movement. First, attention will be paid to the fact that sequels to some of the most authoritative Neo-Confucian texts, such as the Reflections on Things at Hand (Jinsi lu) and Elementary Learning (Sohak), continued to appear in the Chosŏn period. The publication of sequels to Reflections was part of a trend to establish a canon by systematizing the Korean Neo-Confucian tradition within the format of the Reflections, and thereby situate Korean Neo-Confucianism as the succeessor of the Neo-Confucian canons of the Six Classics, Four Books, and Reflections. The publication of the sequels to Elementary Learning was part of a trend to popularize Korean Neo-Confucianism by organizing it within the format of the Elementary Learning and thus propagate Neo-Confucian ethics throughout the various strata of society. If these sequels were efforts to systematize the tradition of Korean Neo-Confucianism in a scholarly format, the encounter of Korean Neo-Confucianism with modernity led to undertakings that sought to engage with this new reality through the production of the Kugyŏng yŏnŭi (Extensive exposition of the Nine Canons). In this work, we can identify attempts by Korean Neo-Confucianists to communicate with the contemporary currents of modernity. This article reflects on the historical significance of the academic trends of nineteenth-century Korean Neo-Confucianism, which can be characterized as canonization, popularization, and contemporization. It thus seeks to overcome the wijŏng ch’ŏksa framework and give justice to the changes that Korean Neo-Confucianism underwent during this period.

Recent object detectors find instances while categorizing candidate regions. As each region is evaluated independently, the number of candidate regions from a detector is usually larger than the number of objects. Since the final goal of detection is to assign a single detection to each object, a heuristic algorithm, such as non-maximum suppression (NMS), is used to select a single bounding box for an object. While simple heuristic algorithms are effective for stand-alone objects, they can fail to detect overlapped objects. In this paper, we address this issue by training a network to distinguish different objects using the relationship between candidate boxes. We propose an instance-aware detection network (IDNet), which can learn to extract features from candidate regions and measure their similarities. Based on pairwise similarities and detection qualities, the IDNet selects a subset of candidate bounding boxes using instance-aware determinantal point process inference (IDPP). Extensive experiments demonstrate that the proposed algorithm achieves significant improvements for detecting overlapped objects compared to existing state-of-the-art detection methods on the PASCAL VOC and MS COCO datasets.

Race of interviewer effects are presumed to occur in surveys because respondents answer questions differently depending on interviewer race. This article explored an alternative explanation: differential respondent recruitment. Data from telephone interviews conducted during the 2008 U.S. Presidential election campaign by major survey organizations (ABC News/Washington Post, CBS News/New York Times, and Gallup) indicate that African-American interviewers were more likely to elicit statements of the intent to vote for Barack Obama than White interviewers. But this effect occurred because African-American interviewers were more likely than White interviewers to elicit survey participation by African-American respondents, and/or White interviewers were more likely to elicit participation by White respondents. Thus, differences between interviewers in terms of responses obtained are not necessarily because of respondent lying. Accepted version

© 2014. The 70-kDa heat shock protein (HSP70) is known to protect the brain from injury through multiple mechanisms. We investigated the effect of pharmacological HSP70 induction in experimental traumatic brain injury (TBI). 3-month-old male C57/B6 mice were given 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) intraperitoneally (IP, 2. mg/kg) or intracerebroventricularly (ICV, 1. μg/kg) to determine whether HSP70 could be induced in the brain. Mice were subjected to TBI via cortical controlled impact, and were treated with 17-AAG (or vehicle) IP according to one of two treatment regimens: (1) 2. mg/kg at the time of injury, (2) a total of three doses (4. mg/kg) at 2 and 1. d prior to TBI and again at the time of injury. Brains were assessed for HSP70 induction, hemorrhage volume at 3. d, and lesion size at 14. d post-injury. Immunohistochemistry showed that both IP and ICV administration of 17-AAG increased HSP70 expression primarily in microglia and in a few neurons by 24. h but not in astrocytes. 17-AAG induced HSP70 in injured brain tissue as early as 6. h, peaking at 48. h and largely subsiding by 72. h after IP injection. Both treatment groups showed decreased hemorrhage volume relative to untreated mice as well as improved neurobehavioral outcomes. These observations indicate that pharmacologic HSP70 induction may prove to be a promising treatment for TBI.

Apoptosis is a cell death pathway that is activated in ischemic stroke. The interaction between Fas and its ligand (FasL) initiates a complex pattern of intracellular events involving the recruitment of specific adaptor proteins and the development of apoptosis. We recently reported that dynamin is increased after experimental stroke, and its inhibition improves neurological outcome. Dynamin has been shown to transport Fas from the endoplasmic reticulum to the cell surface where it can be bound by its ligand, FasL. Hypothermia has been shown to improve outcome in numerous stroke models, and this protection is associated with reduced apoptosis and Fas expression. To explore the contribution of dynamin to hypothermic neuroprotection, we subjected mice to distal middle cerebral artery occlusion (dMCAO) and applied one of two cooling paradigms: one where cooling began at the onset of dMCAO (early hypothermia) and another where cooling began 1 hour later (delayed hypothermia), compared with normothermia (Norm). Both cooling paradigms reduced numbers of apoptotic cells, as well as Fas and dynamin compared with Norm. Fas and dynamin were co-expressed in neurons. Neuronal cultures were exposed to oxygen glucose deprivation. Hypothermia decreased dynamin as well as surface expression of Fas, and this correlated to reduced cell death. The results of this study suggest that dynamin may participate in the Fas-mediated apoptotic pathway, and its reduction may be linked to hypothermic neuroprotection.

Aim Livin, a member of the inhibitors of apoptosis proteins, is expressed in variable cancers, and its expression is considered a poor prognostic marker. The aims of this study were to observe the effect of Livin on the behaviors of hepatocellular carcinoma (HCC) cells and to evaluate its expression in HCC tissues and its relation to prognosis. Methods The biological effects of Livin on tumor cell behavior were investigated using siRNA in HepG2 and Chang cells. Migration, invasion and proliferation assays were performed. Flow cytometric analyses and western blotting were used to evaluate the impact of Livin on apoptosis and the cell cycle. In addition, western blotting and immunohistochemistry were used to investigate Livin expression in HCC tissues. Results Livin knockdown suppressed tumor cell migration, invasion and proliferation in HCC cells, and increased the proportion of apoptotic cells as compared with scrambled siRNA-transfected HCC cells. Furthermore, Livin knockdown resulted in the activation of caspases and increased apoptosis. In addition, Livin knockdown modulated cell cycle regulatory protein levels such as decrease of cyclins and cyclin-dependent kinase (CDK) level, and increase of CDK inhibitor (CDKI) level in HCC cells. The Livin protein level was significantly elevated in HCC tissues as compared with normal hepatic tissues. However, Livin expression was not found to be associated with clinicopathological parameters, which included patient survival. Conclusion These results suggest that Livin is associated with invasive and oncogenic phenotypes of human HCC cells.

Past studies of elections have shown that candidates whose names were listed at the beginning of a list on a ballot often received more votes by virtue of their position. This article tests speculations about the cognitive mechanisms that might be responsible for producing the effect. In an experiment embedded in a large national Internet survey, participants read about the issue positions of two hypothetical candidates and voted for one of them in a simulated election in which candidate name order was varied. The expected effect of position appeared and was strongest (1) when participants had less information about the candidates on which to base their choices, (2) when participants felt more ambivalent about their choices, (3) among participants with more limited cognitive skills, and (4) among participants who devoted less effort to the candidate evaluation process. The name-order effect was greater among left-handed people when the candidate names were arrayed horizontally, but there was no difference between left- and right-handed people when the names were arrayed vertically. These results reinforce some broad theoretical accounts of the cognitive process that yield name-order effects in elections.

The detection of coliforms requires incubation in a laboratory, generally powered using electricity. In many parts of the developing world, however, external energy sources such as electricity are not readily available. To develop a fast, reliable method for detecting coliforms in water without an external energy source, we assessed the efficacy of six test kits for the identification of coliforms in water samples. To assess the possibility of using body temperature as the sole source of heat for incubation, bacterial samples were then mixed with the enzymatic test kit reagent and attached to the human body surface using a patch system. The patches were attached to the bodies of volunteers for 24 hours and the practicality and accuracy of the patches were assessed. Coliforms were detected within 24 hours in all patches. This innovation will facilitate the testing of water quality by researchers and by economically disadvantaged people without electricity.

Early growth response-1 (Egr-1) is implicated in the regulation of cell growth, proliferation, differentiation and apoptosis. Egr-1 is considered tobe either a tumor-suppressor or tumor-promoter, depending on the cell type and environment. The aim of the present study was to evaluate the expression of Egr-1 in colorectal cancer and its correlation with tumor cell proliferation, apoptosis and clinicopathological features. The expression of Egr-1 in colorectal cancer tissues was investigated by reverse transcription-polymerase chain reaction (RT-PCR), western blotting and immunohistochemistry. Apoptosis was detected by terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), and cellular proliferative activity was evaluated by immunohistochemical staining with the Ki-67 antibody. Egr-1 expression was significantly elevated in colorectal cancer tissues, when compared to that in the paired normal mucosa at the mRNA and protein levels. In addition, Egr-1 expression was significantly increased in the metastatic lymph node tissues, when compared to that in the non‑metastatic lymph node tissues at the protein level. The mean Ki-67 labeling index (KI) and apoptotic index (AI) values for 158 tumors were 53.6±15.4 and 9.0±1.0, respectively. Higher KI values were significantly associated with distant metastasis. Lower AI values were significantly associated with lymph node metastasis. However, KI or AI values were not associated with patient survival. The mean KI value of Egr-1-positive tumors was significantly higher than that of Egr-1-negative tumors. However, there was no significant difference between Egr-1 expression and AI value. Positive expression of Egr-1 was significantly associated with age, lymphovascular invasion, lymph node and distant metastasis, tumor stage and poor survival. These results indicate that Egr-1 may be associated with colorectal cancer progression via tumor cell proliferation.

The effects of anger and information were experimentally tested in a small group deliberation setting. The participants were randomly assigned to one of four conditions varying in the level of induced anger and amount of information they received. After reading about a controversial local issue, they engaged in a group discussion about the topic. Content analysis revealed each individual’s level of participation. More informed participants expressed more opinions during deliberation than less informed participants. Participants made to feel angry were also more active than those in the control condition, but to a lesser degree than the more informed participants. Structural equation modeling suggested that the effect of anger on postdeliberation argument repertoire and knowledge was more direct, whereas the effect of information was mediated by active participation during deliberation.

The early growth response-1 (Egr-1) is crucial in many cell regulatory processes related to the progression of human cancers. Its overexpression has been demonstrated in variable human cancers and may have prognostic significance. The aims of this current study were to evaluate whether Egr-1 affects invasive and oncogenic phenotypes of human gastric cancer cells, and to examine the relationships between its expression and various clinicopathological parameters, including survival in human gastric cancer patients. We investigated the biologic role of Egr-1 in tumor cell behavior by using a small interfering RNA in human gastric cancer cell lines, AGS and TMK1. The expression of Egr-1 by reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and immunohistochemistry was investigated in human gastric cancer tissues. The knockdown of Egr-1 suppressed tumor cell migration and invasion in AGS and TMK1 cells. Egr-1 expression was significantly increased in human gastric cancer and metastatic lymph node tissues compared to the normal gastric mucosa and non-metastatic lymph node tissues. Positive expression of Egr-1 was significantly associated with tumor size, depth of invasion, lymph node metastasis, tumor stage and poor survival. These results indicate that Egr-1 is associated with human gastric cancer progression through the alteration of tumor cell behavior, such as migration and invasion. Egr-1 expression may help in predicting the clinical outcomes of human gastric cancer patients.

Livin is one of the most important members of the inhibitor of apoptosis protein family. It is overexpressed in several types of tumors and may have prognostic significance. The present study investigated the biological role of Livin in the oncogenic behavior of gastric cancer cells, the expression of Livin in gastric cancer tissue and the relationship of its expression with various clinicopathological parameters and patient survival. Small interfering RNA blocked Livin gene expression in AGS and SNU638 human gastric cancer cell lines. The expression of Livin was investigated in gastric cancer tissues by RT-PCR, western blotting and immunohistochemistry. The associations with various clinicopathological parameters and survival were analyzed. Livin knockdown inhibited tumor cell migration, invasion and proliferation in AGS and SNU638 cells. Livin knockdown induced apoptosis by activating caspase-3, caspase-7 and PARP. Livin knockdown induced cell cycle arrest by a decrease in cyclin D1, cyclin-dependent kinase 4 and 6 and an increase in expression of p21 and p27. The ERK1/2 and JNK signaling pathways were inhibited by Livin knockdown. Livin expression was upregulated in gastric cancer tissues at the mRNA and protein levels. However, no significant correlation was found between Livin expression and various clinicopathological parameters including survival. In conclusion, Livin expression may be important in the alteration of invasive and oncogenic phenotypes of gastric cancer cells. The prognostic relevance of Livin remains unclear.

Background and Purpose— The 70-kDa heat shock protein (Hsp70) protects brain cells in models of cerebral ischemia. Proteomic screening of mice subjected to middle cerebral artery occlusion identified dynamin as a major downregulated protein in Hsp70-overexpressing mice (Hsp70 transgenic mice). Dynamin-1 is expressed in neurons and participates in neurotransmission, but also transports the death receptor Fas to the cell surface, where it can be bound by its ligand and lead to apoptosis. Methods— Mice were subjected to distal middle cerebral artery occlusion. Neuro-2a cells were subjected to oxygen glucose deprivation. Hsp70 transgenic and Hsp70-deficient (Hsp70 knockout) mice were compared with wild-type mice for histological and behavioral outcomes. Some mice and neuro-2a cell cultures were given dynasore, a dynamin inhibitor. Results— Hsp70 transgenic mice had better outcomes, whereas Hsp70 knockout mice had worse outcomes compared with wild-type mice. This correlated with decreased and increased dynamin expression, respectively. Dynamin colocalized to neurons and Fas, with higher Fas levels and increased caspase-8 expression. Hsp70 induction in neuro-2a cells was protected from oxygen glucose deprivation, while downregulating dynamin and Fas expression. Further, dynamin inhibition was found to be neuroprotective. Conclusions— Dynamin may facilitate Fas-mediated apoptotic death in the brain, and Hsp70 may protect by preventing this trafficking. Dynamin should be explored as a new therapeutic target for neuroprotection.

One of the primary challenges in the field of psychiatric genetics is the lack of anin vivomodel system in which to functionally validate candidateneuropsychiatricriskgenes (NRGs) in a rapid and cost-effective manner1−3. To overcome this obstacle, we performed a candidate-based RNAi screen in whichC. elegansorthologs of human NRGs were assayed for dendritic arborization and cell specification defects usingC. elegansPVD neurons. Of 66 NRGs, identified via exome sequencing of autism (ASD)4or schizophrenia (SCZ)5−9probands and whose mutations arede novoand predicted to result in a complete or partial loss of protein function, theC. elegansorthologs of 7 NRGs were found to be required for proper neuronal development and represent a variety of functional classes, including transcriptional regulators and chromatin remodelers, molecular chaperones, and cytoskeleton-related proteins. Notably, the positive hit rate, when selectively assayingC. elegansorthologs of ASD and SCZ NRGs, is enriched >14-fold as compared to unbiased RNAi screening10. Furthermore, we find that RNAi phenotypes associated with the depletion of NRG orthologs is recapitulated in genetic mutant animals, and, via genetic interaction studies, we show that the NRG ortholog of ANK2,unc-44, is required for SAX-7/MNR-1/DMA-1 signaling. Collectively, our studies demonstrate thatC. elegansPVD neurons are a tractable model in which to discover and dissect the fundamental molecular mechanisms underlying neuropsychiatric disease pathogenesis.

Inflammation which accompanies traumatic brain injury (TBI) can exacerbate neurological deficits. Thus, anti-inflammatory treatments have the potential to improve outcome. Angiotensin II receptor type 1 (ART1) mediates vasoconstriction, and its inhibition has been widely used to treat hypertension. However, recent work has suggested that it may also modulate apoptosis, and neuroinflammation. Thus, treatment with already available ART1 blockers may have additional neuroprotective value. We explore the contribution of ART1 to neuroprotection and brain hemorrhage in a model of TBI. Male, wildtype (Wt) and ART1 knockout (Ko) mice were subjected to TBI using controlled cortical impact (CCI). This model leads to reproducible traumatic brain injury with disruption of motor function and hemorrhage into the area of injury. Sensorimotor function (adhesive removal & elevated body swing tests), brain hemorrhage and lesion size were assessed at 3, 7 and 14 days. To explore the clinical relevance of ART1 in brain injury, we also gave Wt mice an ATR1 inhibitor (candesartan, 0.1mg/kg IP). We found that ATR1 deficient mice were protected from CCI as evidenced by decreased lesion and hemorrhage volumes (decreases of ∼40% in lesion size amongst Ko mice, n=6/group, p

We propose a model of how messages about groups one personally dislikes affect individual attitudes. We build upon theories of message persuasion and out-group acceptance to account for evidence type (numerical vs. narrative), facilitating conditions (encouraging empathy vs. objectivity), and the underlying mechanisms (immersion). We test this model in a pretest-posttest experiment, in which a sample of Americans ( N = 601) read counter-attitudinal commentaries below articles presenting either narrative or numerical evidence about illegal immigrants or same-sex couples. Narratives led to greater message acceptance and greater immersion, especially in the empathetic condition. In turn, numerical messages led to self-perceived attitude change in the objective condition. Persuasive effects of narratives in the empathetic, but not the objective, condition were mediated by immersion.

The 70-kDa heat shock protein (Hsp70) is thought to protect the brain from a variety of insults. Although the mechanism has been largely limited to its chaperone functions, recent work indicates that Hsp70 also modulates inflammatory pathways. Brain injury and ischemia are associated with an immune response that is largely innate. Hsp70 appears to suppress this response and lead to improved neurological outcome. However, most of this work has relied on the use of genetic mutant models or Hsp70 overexpression using gene transfer or heat stress, thus limiting its translational utility. A few compounds have been studied by various disciplines which, through their ability to inhibit Hsp90, can cause induction of Hsp70. The investigation of Hsp70-inducing pharmacological compounds has obvious clinical implications in terms of potential therapies to mitigate neuroinflammation and lead to neuroprotection from stroke or traumatic brain injury. This review will focus on the inflammation modulating properties of Hsp70, and the current literature surrounding the pharmacological induction in acute neurological injury models with comments on potential applications at the clinical level.

This study explores the implications of political weblogs for theories of mediated public deliberation. Guided by contemporary questions surrounding the internet and the public sphere, we examine blog and newspaper coverage of the nomination and confirmation to the U.S. Supreme Court of Samuel Alito with an eye toward further development of theories of mass deliberation. Specifically, we pursue questions concerning volume of coverage, ideological polarization, and interactive features in the blogosphere, using newspaper coverage as a point of reference. Data come from content analyses of newspaper stories mentioning Alito in the headline or lead paragraphs from the initial nomination announcement through final confirmation, as well as archival impressions of blog posts featuring hyperlinks to the newspaper stories. Our analysis suggests that blogs may enhance as well as complicate processes of mediated deliberation. We conclude by discussing empirical and conceptual implications of these findings for future research on the role of blogs in the contemporary public sphere.

Angiogenesis and lymphangiogenesis are involved in the dissemination of tumor cells from solid tumors to regional lymph nodes and various distant sites. KAI1 COOH-terminal interacting tetraspanin (KITENIN) contributes to tumor progression and poor clinical outcomes in various cancers including colorectal cancer. The aim of the present study was to evaluate whether KITENIN affects tumor angiogenesis and lymphangiogenesis in colorectal cancer. A KITENIN small interfering RNA vector was used to silence KITENIN expression in colorectal cancer cell lines including DLD1 and SW480 cells. To evaluate the ability of KITENIN to induce angiogenesis and lymphangiogenesis in human umbilical vein endothelial cells (HUVECs) and lymphatic endothelial cells (HLECs), we performed Matrigel invasion and tube formation assays. Immunohistochemistry was used to determine the expression of KITENIN in colorectal cancer tissues. Angiogenesis and lymphangiogenesis were evaluated by immunostaining with CD34 and D2-40 antibodies. KITENIN silencing inhibited both HUVEC invasion and tube formation in the DLD1 and SW480 cells. KITENIN silencing led to decreased expression of the angiogenic inducers vascular endothelial growth factor (VEGF)-A and hypoxia-inducible factor-1α and increased expression of the angiogenic inhibitor angiostatin. KITENIN silencing did not inhibit either HLEC invasion or tube formation in all tested cells, but it resulted in decreased expression of the lymphangiogenic inducer VEGF-C. KITENIN expression was significantly associated with tumor stage, depth of invasion, lymph node and distant metastases and poor survival. The mean microvessel density was significantly higher in the KITENIN-positive tumors than that in the KITENIN-negative tumors. However, the mean lymphatic vessel density of KITENIN-positive tumors was not significantly higher than that of the KITENIN-negative tumors. These results suggest that KITENIN promotes tumor progression by enhancing angiogenesis in colorectal cancer.

Interleukin-18 (IL-18) is a pleiotropic, pro-inflammatory cytokine that is capable of promoting the Th1 response. A predominant Th1 response induces chronic and persistent inflammatory changes in the gastric mucosa in response to Helicobacter pylori (H. pylori) infection. The aim of this study was to investigate the potential association between IL-18 gene polymorphisms and susceptibility to H. pylori infection in the Korean population. A total of 678 subjects who underwent a routine health check-up were enrolled. The IL-18 gene polymorphisms at positions −656, −607, −137, +113, and +127 were genotyped. H. pylori positivity was demonstrated in 456 subjects (67.3%). The allele frequencies of IL-18 gene polymorphisms at position −137 (rs187238) were different based on the status of H. pylori infection (G vs. C, adjusted OR 0.64 CI: 0.47–0.87, P = 0.005). The results indicate that the genetic variants in the IL-18 gene may be associated with susceptibility to H. pylori infection in the Korean population, suggesting that IL-18 plays a role in the pathogenesis of H. pylori-associated diseases. However, this finding requires further replication and validation.

© Published 2014. This article is a U.S. Government work and is in the public domain in the USA. As the resident immune cells of the central nervous system, microglia rapidly respond to brain insults, including stroke and traumatic brain injury. Microglial activation plays a major role in neuronal cell damage and death by releasing a variety of inflammatory and neurotoxic mediators. Their activation is an early response that may exacerbate brain injury and many other stressors, especially in the acute stages, but are also essential to brain recovery and repair. The full range of microglial activities is still not completely understood, but there is accumulating knowledge about their role following brain injury. We review recent progress related to the deleterious and beneficial effects of microglia in the setting of acute neurological insults and the current literature surrounding pharmacological interventions for intervention.

Epithelial-mesenchymal transition (EMT) is a critical process that occurs during cancer progression, and cancer stem cells have been shown to acquire the EMT phenotype. Myeloid cell leukemia-1 (Mcl-1) has been implicated in cancer progression and is overexpressed in a variety of human cancers. However, the interaction between Mcl-1 and EMT in human gastric cancer (GC) is unclear. We investigated the impact of Mcl-1 expression levels on EMT and the underlying signaling pathways in human GC cells. We used the human GC cell lines, AGS and SNU638, and small interfering RNAs (siRNAs) to evaluate the effects of Mcl-1 knockdown on cell adhesion, migration and invasion. Expression of Mcl-1 and other target genes was determined using reverse transcription-polymerase chain reaction assays and western blotting. The results revealed that expression levels of Mcl-1 mRNA and protein in the AGS and SNU638 cells were reduced following transfection with Mcl-1 siRNAs. Knockdown of Mcl-1 led to increased cellular adhesion to fibronectin and collagen. Expression levels of vimentin, MMP-2, MMP-9 and Snail protein were decreased following knockdown of Mcl-1. However, expression of E-cadherin was increased in the AGS cells following knockdown of Mcl-1. The expression of cancer stemness markers, such as CD44 and CD133, was not altered by knockdown of Mcl-1. Knockdown of Mcl-1 suppressed tumor cell migration and invasion in both human GC cell lines. Signaling cascades, including the β-catenin, MEK1/2, ERK1/2 and p38 pathways, were significantly blocked by knockdown of Mcl-1. Our results indicate that Mcl-1 expression induces EMT via β-catenin, MEK1/2 and MAPK signaling pathways, which subsequently stimulates the invasive and migratory capacity of human GC cells.

Intact protein masses can be measured directly from immobilized pH gradient (IPG) isoelectric focusing (IEF) gels loaded with mammalian and prokaryotic samples, as demonstrated here with murine macrophage and Methanosarcina acetivorans cell lysates. Mass accuracy and resolution is improved by employing instruments which decouple the desorption event from mass measurement; e.g., quadrupole time-of-flight instruments. MALDI in-source dissociation (ISD) is discussed as a means to pursue top-down sequencing for protein identification. Methods have been developed to enzymatically digest all proteins in an IEF gel simultaneously, leaving the polyacrylamide gel attached to its polyester support. By retaining all gel pieces and their placement relative to one another, sample handling and tracking are minimized, and comparison to 2-D gel images is facilitated. MALDI-MS and MS/MS can then be performed directly from dried, matrix-treated IPG strips following whole-gel trypsin digestion, bottom-up methodology. Side-to-side proteomics, highlighting the link between virtual and classical 2-D gel electrophoresis, is introduced to describe a method whereby intact masses are measured from one side (the IEF gel), while proteins are identified based on analyses performed from the other side (the SDS-PAGE gel).

Myeloid cell leukemia-1 (Mcl-1) is a highly expressed anti-apoptotic Bcl-2 protein in cancer. Therefore, inhibition of its expression induces apoptosis in cancer cells and enhances sensitivity to cancer treatment. The aims of this study were to evaluate whether Mcl-1 affects the oncogenic behaviors of colorectal cancer cells, and to document the relationship of its expression with various clinicopathological parameters in colorectal cancer. Mcl-1 knockdown induced apoptosis by activating cleaved caspase-3 and -9, and increasing the expression of the pro-apoptotic protein, PUMA. Mcl-1 knockdown induced cell cycle arrest by decreasing cyclin D1, CDK4 and 6, and by increasing p27 expression. Mcl-1 knockdown decreased both endothelial cell invasion and tube formation, and decreased the expression of VEGF. The phosphorylation level of STAT3 was decreased by Mcl-1 knockdown. The mean apoptotic index value of Mcl-1 positive tumors was significantly lower than that of Mcl-1 negative tumors. The mean microvessel density value of Mcl-1 positive tumors was significantly higher than that of negative tumors. Mcl-1 expression was significantly increased in colorectal cancer, also associated with tumor stage, lymph node metastasis, and poor survival. These results indicate Mcl-1 is associated with tumor progression through its inhibition of apoptosis and enhancement of angiogenesis in colorectal cancer.

Object Ischemic brain injury is the leading cause for death and long-term disability in patients who suffer cardiac arrest and embolic stroke. Excitotoxicity and subsequent Ca2+-overload lead to ischemic neuron death. We explore a novel mechanism concerning the role of the excitatory extracellular calcium-sensing receptor (CaSR) in the induction of ischemic brain injury. Method Mice were exposed to forebrain ischemia and the actions of CaSR were determined after its genes were ablated specifically in hippocampal neurons or its activities were inhibited pharmacologically. Since the CaSR forms a heteromeric complex with the inhibitory type B γ-aminobutyric acid receptor 1 (GABABR1), we compared neuronal responses to ischemia in mice deficient in CaSR, GABABR1, or both, and in mice injected locally or systemically with a specific CaSR antagonist (or calcilytic) in the presence or absence of a GABABR1 agonist (baclofen). Results Both global and focal brain ischemia led to CaSR overexpression and GABABR1 downregulation in injured neurons. Genetic ablation of Casr genes or blocking CaSR activities by calcilytics rendered robust neuroprotection and preserved learning and memory functions in ischemic mice, partly by restoring GABABR1 expression. Concurrent ablation of Gabbr1 gene blocked the neuroprotection caused by the Casr gene knockout. Coinjection of calcilytics with baclofen synergistically enhanced neuroprotection. This combined therapy remained robust when given 6 h after ischemia. Interpretation Our study demonstrates a novel receptor interaction, which contributes to ischemic neuron death through CaSR upregulation and GABABR1 downregulation, and feasibility of neuroprotection by concurrently targeting these two receptors.

Traumatic brain injury (TBI) leads to acute functional deficit in the brain. Molecular events underlying TBI remain unclear. In mouse brains, we found controlled cortical impact (CCI) injury induced overexpression of the extracellular calcium-sensing receptor (CaSR), which is known to stimulate neuronal activity and accumulation of intracellular Ca2+ and concurrent down-regulation of type B or metabotropic GABA receptor 1 (GABA-B-R1), a prominent inhibitory pathway in the brain. These changes in protein expression preceded and were closely associated with the loss of brain tissue, as indicated by the increased size of cortical cavity at impact sites, and the development of motor deficit, as indicated by the increased frequency of right-biased swing and turn in the CCI mice. Mild hypothermia, an established practice of neuroprotection for brain ischemia, partially but significantly blunted all of the above effects of CCI. Administration of CaSR antagonist NPS89636 mimicked hypothermia to reduce loss of brain tissue and motor functions in the CCI mice. These data together support the concept that CaSR overexpression and overactivity play a causal role in potentiating TBI potentially by stimulating excitatory neuronal responses and by interfering with inhibitory GABA-B-R signaling and that the CaSR could be a novel target for neuroprotection against TBI. © 2013 Mary Ann Liebert, Inc.

Hypothermia improves neurological outcome from cardiac arrest. The mechanisms of protection are multifold, but identifying some may be useful in exploring potential therapeutic targets. The extracellular calcium-sensing receptor (CaSR) was originally found in parathyroid cells in which the receptor senses minute changes in extracellular [Ca(2+)] and promotes Ca(2+) influx and intracellular Ca(2+) release. The CaSR is broadly expressed in the CNS and colocalized with the inhibitory γ-aminobutyric acid-B receptor 1 (GABA-B-R1). In hippocampal neurons, GABA-B-R1 heterodimerizes with CaSR and suppresses CaSR expression. To study the interplay between these two receptors in the development of ischemic cell death and neuroprotection by hypothermia, we subjected C57/BL6 mice to global cerebral ischemia by performing bilateral carotid artery occlusion (10 min) followed by reperfusion for 1-3 days with or without therapeutic hypothermia (33°C for 3 h at the onset of reperfusion). Terminal deoxynucleotidyl transferase dUTP nick end labeling staining and immunohistochemistry showed that forebrain ischemia increased CaSR expression, decreased GABA-B-R1 expression, and promoted cell death. These changes were particularly evident in hippocampal neurons and could be reversed by mild hypothermia. The induction of CaSR, along with reciprocal decreases in GABA-B-R1 expression, may together potentiate ischemic neuronal death, suggesting a new therapeutic target for treatment of ischemic brain injury.

Objective: The present study aims to examine gender differences in attitudes toward professional psychological help–seeking behavior and how gender differences could be affected by other cultural factor such as race. Participants: The authors selected studies that involved undergraduate and graduate students as samples, making the total number of participants in this meta-analysis 5,713. Methods: Statistical procedures were administrated by the MIX (Meta-analysis with Interactive eXplanations) program, which does meta-analyses. Results and Conclusions: The results indicated that gender itself was a significant predictor on attitudes toward seeking professional psychological help. In addition, individual's cultural background (eg, Western versus non-Western ethnicity) moderated the gender differences on attitudes toward seeking professional psychological help. Practical implications for mental health professionals in college settings were discussed.

The expression of myeloid cell leukemia-1 (Mcl‑1), a member of the anti-apoptotic Bcl-2 protein family, has been associated with tumor progression and adverse patient outcome. The aims of current study were to evaluate whether Mcl-1 affects the survival or death of gastric cancer cells, and to investigate the prognostic value of its expression in gastric cancer. PcDNA3.1-Mcl-1 expression and Mcl-1 siRNA vectors were used to overexpress and silence Mcl-1 expression in gastric cancer cell lines including SNU638 and TMK1, respectively. Immunohistochemistry was used to determine the expression of Mcl-1 in gastric cancer tissues. Apoptosis was determined by the TUNEL assay, and cell proliferation was determined by immunostaining with a Ki-67 antibody. Mcl-1 knockdown induced apoptosis through the upregulation of caspase-3, and -7, and PARP activity, and the release of Smac/DIABLO and Omi/HtrA2 into the cytoplasm. Additionally, cell cycle arrest occurred due to decrease of cyclin D1, cell division cycle gene 2 (cdc2), and cyclin-dependent kinase 4 and 6. In contrast, overexpression of Mcl-1 inhibited apoptosis and cell cycle arrest. Mcl-1 knockdown did not suppress tumor cell proliferation in gastric cancer cells, whereas overexpression of Mcl-1 enhanced tumor cell proliferation. The JAK2 and STAT3 signaling cascades were significantly blocked by Mcl-1 knockdown. The mean Ki-67 labeling index (KI) value of Mcl-1 positive tumors was significantly lower than that of Mcl-1 negative tumors. However, there was no significant difference between Mcl-1 expression and the apoptotic index (AI). Mcl-1 expression was significantly increased in gastric cancer tissues compared to normal gastric mucosa tissues, and was associated with age, tumor size, stage, depth of invasion, lymph node metastasis and poor survival. Our study showed that Mcl-1 regulates the cell growth and might be a potential prognostic marker for gastric cancer.

Most somatic cells encounter an inevitable destiny, senescence. Little progress has been made in identifying small molecules that extend the finite lifespan of normal human cells. Here we show that the intrinsic 'senescence clock' can be reset in a reversible manner by selective modulation of the ataxia telangiectasia-mutated (ATM) protein and ATM- and Rad3-related (ATR) protein with a small molecule, CGK733. This compound was identified by a high-throughput phenotypic screen with automated imaging. Employing a magnetic nanoprobe technology, magnetism-based interaction capture (MAGIC), we identified ATM as the molecular target of CGK733 from a genome-wide screen. CGK733 inhibits ATM and ATR kinase activities and blocks their checkpoint signaling pathways with great selectivity. Consistently, siRNA-mediated knockdown of ATM and ATR induced the proliferation of senescent cells, although with lesser efficiency than CGK733. These results might reflect the specific targeting of the kinase activities of ATM and ATR by CGK733 without affecting any other domains required for cell proliferation.