Social consequences of subclinical negative symptoms: An EMG study of facial expressions within a social interaction.

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Riehle, Marcel; Lincoln, Tania M

2017-06-01

The negative symptoms of schizophrenia are related to lower social functioning even in non-clinical samples, but little is known about the distinct social consequences of motivational and expressive negative symptoms. In this study we focused on expressive negative symptoms and examined how these symptoms and varying degrees of pro-social facial expressiveness (smiling and mimicry of smiling) relate to the social evaluations by face-to-face interaction partners and to social support. We examined 30 dyadic interactions within a sample of non-clinical participants (N = 60) who were rated on motivational and expressive negative symptoms with the Clinical Assessment Interview for Negative Symptoms (CAINS). We collected data on both interaction partners' smiling-muscle (zygomaticus major) activation simultaneously with electromyography and assessed the general amount of smiling and the synchrony of smiling muscle activations between interaction partners (mimicry of smiling). Interaction partners rated their willingness for future interactions with each other after the interactions. Interaction partners of participants scoring higher on expressive negative symptoms expressed less willingness for future interactions with these participants (r = -0.37; p = 0.01). Smiling behavior was negatively related to expressive negative symptoms but also explained by motivational negative symptoms. Mimicry of smiling and both negative symptom domains were also associated with participants' satisfaction with their social support network. Non-clinical sample with (relatively) low levels of symptoms. Expressive negative symptoms have tangible negative interpersonal consequences and directly relate to diminished pro-social behavior and social support, even in non-clinical samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

The relationship of positive and negative expressiveness to the processing of emotion information.

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Knyazev, Gennady G; Barchard, Kimberly A; Razumnikova, Olga M; Mitrofanova, Larisa G

2012-06-01

The tendency to express emotions non-verbally is positively related to perception of emotions in oneself. This study examined its relationship to perception of emotions in others. In 40 healthy adults, EEG theta synchronization was used to indicate emotion processing following presentation of happy, angry, and neutral faces. Both positive and negative expressiveness were associated with higher emotional sensitivity, as shown by cortical responses to facial expressions during the early, unconscious processing stage. At the late, conscious processing stage, positive expressiveness was associated with higher sensitivity to happy faces but lower sensitivity to angry faces. Thus, positive expressiveness predisposes people to allocate fewer attentional resources for conscious perception of angry faces. In contrast, negative expressiveness was consistently associated with higher sensitivity. The effects of positive expressiveness occurred in cortical areas that deal with emotions, but the effects of negative expressiveness occurred in areas engaged in self-referential processes in the context of social relationships. © 2012 The Authors. Scandinavian Journal of Psychology © 2012 The Scandinavian Psychological Associations.

Expressive Suppression Tendencies, Projection Bias in Memory of Negative Emotions, and Well-Being.

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Chang, Valerie T; Overall, Nickola C; Madden, Helen; Low, Rachel S T

2018-02-01

The current research extends prior research linking negative emotions and emotion regulation tendencies to memory by investigating whether (a) naturally occurring negative emotions during routine weekly life are associated with more negatively biased memories of prior emotional experiences-a bias called projection; (b) tendencies to regulate emotions via expressive suppression are associated with greater projection bias in memory of negative emotions; and (c) greater projection bias in memory is associated with poorer future well-being. Participants (N = 308) completed a questionnaire assessing their general tendencies to engage in expressive suppression. Then, every week for 7 weeks, participants reported on (a) the negative emotions they experienced across the current week (e.g., "This week, I felt 'sad'"), (b) their memories of the negative emotions they experienced the prior week (e.g., "Last week, I felt 'sad'"), and (c) their well-being. First, participants demonstrated significant projection bias in memory: Greater negative emotions in a given week were associated with remembering emotions in the prior week more negatively than those prior emotions were originally reported. Second, projection bias in memory of negative emotions was greater for individuals who reported greater tendencies to regulate emotions via expressive suppression. Third, greater projection bias in memory of negative emotions was associated with reductions in well-being across weeks. These 3 novel findings indicate that (a) current negative emotions bias memory of past emotions, (b) this memory bias is magnified for people who habitually use expressive suppression to regulate emotions, and (c) this memory bias may undermine well-being over time. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Perils of intraoperative neurophysiological monitoring: analysis of "false-negative" results in spine surgeries.

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Tamkus, Arvydas A; Rice, Kent S; McCaffrey, Michael T

2018-02-01

Although some authors have published case reports describing false negatives in intraoperative neurophysiological monitoring (IONM), a systematic review of causes of false-negative IONM results is lacking. The objective of this study was to analyze false-negative IONM findings in spine surgery. This is a retrospective cohort analysis. A cohort of 109 patients with new postoperative neurologic deficits was analyzed for possible false-negative IONM reporting. The causes of false-negative IONM reporting were determined. From a cohort of 62,038 monitored spine surgeries, 109 consecutive patients with new postoperative neurologic deficits were reviewed for IONM alarms. Intraoperative neurophysiological monitoring alarms occurred in 87 of 109 surgeries. Nineteen patients with new postoperative neurologic deficits did not have an IONM alarm and surgeons were not warned. In addition, three patients had no interpretable IONM baseline data and no alarms were possible for the duration of the surgery. Therefore, 22 patients were included in the study. The absence of IONM alarms during these 22 surgeries had different origins: "true" false negatives where no waveform changes meeting the alarm criteria occurred despite the appropriate IONM (7); a postoperative development of a deficit (6); failure to monitor the pathway, which became injured (5); the absence of interpretable IONM baseline data which precluded any alarm (3); and technical IONM application issues (1). Overall, the rate of IONM method failing to predict the patient's outcome was very low (0.04%, 22/62,038). Minimizing false negatives requires the application of a proper IONM technique with the limitations of each modality considered in their selection and interpretation. Multimodality IONM provides the most inclusive information, and although it might be impractical to monitor every neural structure that can be at risk, a thorough preoperative consideration of available IONM modalities is important. Delayed

High ALK mRNA expression has a negative prognostic significance in rhabdomyosarcoma

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Bonvini, P; Zin, A; Alaggio, R; Pawel, B; Bisogno, G; Rosolen, A

2013-01-01

Background: Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase aberrantly expressed in cancer, but its clinical and functional importance remain controversial. Mutation or amplification of ALK, as well as its expression levels assessed by conventional immunohistochemistry methods, has been linked to prognosis in cancer, although with potential bias because of the semi-quantitative approaches. Herein, we measured ALK mRNA expression in rhabdomyosarcoma (RMS) and determined its clinical impact on patients' stratification and outcome. Methods: Specimens were obtained from RMS patients and cell lines, and ALK expression was analysed by quantitative RT–PCR, western blotting, IHC, and copy number analysis. Results: High ALK mRNA expression was detected in the vast majority of PAX3/7-FOXO1-positive tumours, whereas PAX3/7-FOXO1-negative RMS displayed considerably lower amounts of both mRNA and protein. Notably, ALK mRNA distinguished unfavourable PAX3/7-FOXO1-positive tumours from PAX3/7-FOXO1-negative RMS (Ptumour size (PALK mRNA levels were of prognostic relevance by Cox univariate regression analysis and correlated with increased risk of relapse (P=0.001) and survival (P=0.01), whereas by multivariate analysis elevated ALK mRNA expression resulted a negative prognostic marker when clinical stage was not included. Conclusion: Quantitative assessment of ALK mRNA expression helps to improve risk stratification of RMS patients and identifies tumours with adverse biological characteristics and aggressive behaviour. PMID:24149177

Nestin is expressed in HMB-45 negative melanoma cells in dermal parts of nodular melanoma.

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Kanoh, Maho; Amoh, Yasuyuki; Tanabe, Kenichi; Maejima, Hideki; Takasu, Hiroshi; Katsuoka, Kensei

2010-06-01

Nestin, a marker of neural stem cells, is expressed in the stem cells of the mouse hair follicle. The nestin-expressing hair follicle stem cells can differentiate into neurons, glia, keratocytes, smooth muscle cells and melanocytes in vitro. These pluripotent nestin-expressing stem cells are keratin 15 (K15)-negative, suggesting that they are in a relatively undifferentiated state. Recent studies suggest that the epithelial stem cells are important in tumorigenesis, and nestin expression is thought to be important in tumorigenesis. In the present study, we examined the expression of the hair follicle and neural stem cell marker nestin, as well as S-100 and HMB-45, in melanoma. Nestin immunoreactivity was observed in the HMB-45-negative melanoma cells in all five cases of amelanotic nodular melanomas. Moreover, nestin immunoreactivity was observed in the dermal parts in seven of 10 cases of melanotic nodular melanomas. Especially, nestin immunoreactivity was observed in the HMB-45-negative melanoma cells in the dermal parts of all 10 cases of HMB-45-negative amelanotic and melanotic nodular melanomas. On the other hand, nestin expression was negative in 10 of 12 cases of superficial spreading melanoma. These results suggest that nestin is an important marker of HMB-45-negative melanoma cells in the dermal parts of patients with nodular melanoma.

Positive expression of LSD1 and negative expression of E-cadherin correlate with metastasis and poor prognosis of colon cancer.

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Jie, Ding; Zhongmin, Zhang; Guoqing, Liao; Sheng, Liu; Yi, Zhang; Jing, Wen; Liang, Zeng

2013-06-01

The first identified lysine-specific demethylase, LSD1, plays an important role in the metastatic progression of several types of cancer. The aim of this study was to investigate LSD1, E-cadherin, and N-cadherin expression in colon cancer specimens and their clinical significance. The expression of LSD1, E-cadherin, and N-cadherin in colon cancer specimens was determined by immunohistochemistry, and the relationship between the expression of the respective molecules and clinicopathological characteristics was analyzed. The positive expression rates of LSD1, E-cadherin, and N-cadherin in colon cancer specimens were 66.7 % (72/108), 85.2 % (92/108), and 41.7 % (45/108), respectively. LSD1 was significantly more highly expressed in colon cancer specimens classified as high TNM stage lesions and with distant metastasis (P colon cancer specimens classified as high TNM stage lesions and with distant metastasis (P clinical and pathological characteristics (P > 0.05). Correlation analysis revealed that LSD1 expression was negatively correlated with E-cadherin expression (r s = -0.318, P = 0.001), but not evidently correlated with N-cadherin expression (r s = 0.182, P = 0.06). Colon cancer specimens with positive LSD1 expression and negative E-cadherin expression were correlated with significantly lower overall survival. LSD1 showed a significantly higher expression, in contrast to the significantly lower expression of E-cadherin, in colon cancer specimens classified as high TNM stage lesions and with distant metastasis. Positive expression of LSD1 and negative expression of E-cadherin may be predictors of a worse colon cancer prognosis.

mTOR in breast cancer: differential expression in triple-negative and non-triple-negative tumors.

LENUS (Irish Health Repository)

Walsh, S

2012-04-01

Triple-negative breast cancer (TNBC) is defined by the absence of estrogen receptors (ER), progesterone receptors (PR) and overexpression of HER2. Targeted therapy is currently unavailable for this subgroup of breast cancer patients. mTOR controls cancer cell growth, survival and invasion and is thus a potential target for the treatment of patients with TNBC. Using immunohistochemistry, mTOR and p-mTOR were measured in 89 TNBCs and 99 non-TNBCs. While mTOR expression was confined to tumor cell cytoplasm, p-mTOR staining was located in the nucleus, perinuclear area and in the cytoplasm. Potentially important, was our finding that nuclear p-mTOR was found more frequently in triple-negative than non triple-negative cancers (p < 0.001). These results suggest that mTOR may play a more important role in the progression of TNBC compared to non-TNBC. Based on these findings, we conclude that mTOR may be a new target for the treatment of triple-negative breast cancer.

Del-1 Expression as a Potential Biomarker in Triple-Negative Early Breast Cancer.

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Lee, Soo Jung; Lee, Jeeyeon; Kim, Wan Wook; Jung, Jin Hyang; Park, Ho Yong; Park, Ji-Young; Chae, Yee Soo

2018-01-01

A differential diagnostic role for plasma Del-1 was proposed for early breast cancer (EBC) in our previous study. We examined tumoral Del-1 expression and analyzed its prognostic impact among patients with EBC. Del-1 mRNA expression was assessed in breast epithelial and cancer cells. Meanwhile, the tumoral expression of Del-1 was determined based on tissue microarrays and immunohistochemistry results from 440 patients. While a high Del-1 mRNA expression was found in all the breast cancer cell lines, the expression was significantly higher in MDA-MB-231. Tumoral expression of Del-1 was also significantly associated with a negative expression of estrogen receptor or progesterone receptor, and low expression of Ki-67, particularly in the case of triple-negative breast cancer (TNBC) (p breast cancer cell lines exhibited Del-1 expression, the expression rate and intensity were specifically prominent in TNBC. In addition, based on its relationship to an unfavorable histology and worse survival trend, Del-1 could act as a molecular target in TNBC patients. © 2018 S. Karger AG, Basel.

NKG2H-Expressing T Cells Negatively Regulate Immune Responses

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Daniela Dukovska

2018-03-01

Full Text Available The biology and function of NKG2H receptor, unlike the better characterized members of the NKG2 family NKG2A, NKG2C, and NKG2D, remains largely unclear. Here, we show that NKG2H is able to associate with the signaling adapter molecules DAP12 and DAP10 suggesting that this receptor can signal for cell activation. Using a recently described NKG2H-specific monoclonal antibody (mAb, we have characterized the expression and function of lymphocytes that express this receptor. NKG2H is expressed at the cell surface of a small percentage of peripheral blood mononuclear cell (PBMC and is found more frequently on T cells, rather than NK cells. Moreover, although NKG2H is likely to trigger activation, co-cross-linking of this receptor with an NKG2H-specific mAb led to decreased T cell activation and proliferation in polyclonal PBMC cultures stimulated by anti-CD3 mAbs. This negative regulatory activity was seen only after cross-linking with NKG2H, but not NKG2A- or NKG2C-specific monoclonal antibodies. The mechanism underlying this negative effect is as yet unclear, but did not depend on the release of soluble factors or recognition of MHC class I molecules. These observations raise the intriguing possibility that NKG2H may be a novel marker for T cells able to negatively regulate T cell responses.

Differential Language Functioning of Monolinguals and Bilinguals on Positive-Negative Emotional Expression

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Kheirzadeh, Shiela; Hajiabed, Mohammadreza

2016-01-01

The present interdisciplinary research investigates the differential emotional expression between Persian monolinguals and Persian-English bilinguals. In other words, the article was an attempt to answer the questions whether bilinguals and monolinguals differ in the expression of positive and negative emotions elicited through sad and happy…

Facial Expression Recognition via Non-Negative Least-Squares Sparse Coding

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Ying Chen

2014-05-01

Full Text Available Sparse coding is an active research subject in signal processing, computer vision, and pattern recognition. A novel method of facial expression recognition via non-negative least squares (NNLS sparse coding is presented in this paper. The NNLS sparse coding is used to form a facial expression classifier. To testify the performance of the presented method, local binary patterns (LBP and the raw pixels are extracted for facial feature representation. Facial expression recognition experiments are conducted on the Japanese Female Facial Expression (JAFFE database. Compared with other widely used methods such as linear support vector machines (SVM, sparse representation-based classifier (SRC, nearest subspace classifier (NSC, K-nearest neighbor (KNN and radial basis function neural networks (RBFNN, the experiment results indicate that the presented NNLS method performs better than other used methods on facial expression recognition tasks.

Maternal negative emotional expression and discipline in Beijing, China: The moderating role of educational attainment.

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Cheng, Feng; Wang, Yifang; Wu, Xixian; Su, Zhuqing

2018-03-01

The current study shows that parental punitive discipline places children at risk of developing internalizing and externalizing problems. Although some studies have analyzed the reasons for the use of discipline methods, little to no research has analyzed the moderating effects. In this study, we examine the relationship between maternal negative emotional expression and mothers' use of disciplinary methods (psychological aggression, corporal punishment and physical maltreatment) and the moderating effects of educational attainment in Chinese societies. Five hundred and sixteen mothers with preschool-aged children were recruited to participate in this research. The Chinese versions of the Self-Expressiveness in the Family Questionnaire (SEFQ) and the Parent-Child Conflict Tactics Scales (CTSPC) were used to measure the mothers' negative emotional expression and discipline, respectively. The results suggested that the mothers' negative emotional expression was positively related to their disciplinary behaviors. Moreover, maternal educational attainment moderated the association between negative emotional expression and discipline. The findings of the current study highlight the importance of considering how mothers' educational backgrounds may interact with their emotions to influence maternal disciplinary behaviors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Socializing infants towards a cultural understanding of expressing negative affect

DEFF Research Database (Denmark)

Demuth, Carolin

2013-01-01

This article addresses the socialization of emotion expression in infancy. It argues that in order to adequately understand emotion development we need to consider the appraisal of emotion expression through caregivers in mundane, everyday interactions. Drawing on sociocultural and Bakhtinian...... theorizing, it claims that caregivers’ appraisals of infants’ emotion expression are dialogically intertwined with broader speech genres or “communicative genres” of a community and the emotional-volitional tone and normative orientations embedded in them. It aims to investigate how communicative genres......’ expression of negative affect. We found distinct patterns of coconstructing the interaction that point to different normative ori- entations and communicative genres that can be considered to be specific to the two sociocultural contexts. These communicative genres were found to be in line with broader...

Positive, but Not Negative, Facial Expressions Facilitate 3-Month-Olds' Recognition of an Individual Face

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Brenna, Viola; Proietti, Valentina; Montirosso, Rosario; Turati, Chiara

2013-01-01

The current study examined whether and how the presence of a positive or a negative emotional expression may affect the face recognition process at 3 months of age. Using a familiarization procedure, Experiment 1 demonstrated that positive (i.e., happiness), but not negative (i.e., fear and anger) facial expressions facilitate infants' ability to…

Physicians' responses to patients' expressions of negative emotions in hospital consultations: a video-based observational study.

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Mjaaland, Trond A; Finset, Arnstein; Jensen, Bård Fossli; Gulbrandsen, Pål

2011-09-01

Patients express their negative emotions in medical consultations either implicitly as cue to an underlying unpleasant emotion or explicitly as a clear, unambiguous concern. The health provider's response to such cues and concerns is important for the outcome of consultations. Yet, physicians often neglect patient's negative emotions. Most studies of this subject are from primary health care. We aimed to describe how physicians in a hospital respond to negative emotions in an outpatient setting. Ninety six consultations were videotaped in a general teaching hospital. The Verona Coding Definitions of Emotional Sequences was used to identify patients' expression of negative emotions in terms of cue and concern and to code physicians' subsequent responses. Cohen's kappa was used as interrater reliability measure. Acceptable kappa level was set to .60. We observed 163 expressions of negative emotions. In general, the physician responses to patients' cues and concerns did not include follow up or exploration. Concerns more often than cues led to lack of emotional exploration. When patients expressed negative emotions or cues to such, hospital physicians tended to move away from emotional communication, particularly if the emotion was expressed as an explicit concern. Medical training should enable physicians' to explore the patients' emotions in situations where it will improve the medical treatment. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression

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Makino, Yuichi; Cao, Renhai; Svensson, Kristian; Bertilsson, Göran; Asman, Mikael; Tanaka, Hirotoshi; Cao, Yihai; Berkenstam, Anders; Poellinger, Lorenz

2001-11-01

Alteration of gene expression is a crucial component of adaptive responses to hypoxia. These responses are mediated by hypoxia-inducible transcription factors (HIFs). Here we describe an inhibitory PAS (Per/Arnt/Sim) domain protein, IPAS, which is a basic helix-loop-helix (bHLH)/PAS protein structurally related to HIFs. IPAS contains no endogenous transactivation function but demonstrates dominant negative regulation of HIF-mediated control of gene expression. Ectopic expression of IPAS in hepatoma cells selectively impairs induction of genes involved in adaptation to a hypoxic environment, notably the vascular endothelial growth factor (VEGF) gene, and results in retarded tumour growth and tumour vascular density in vivo. In mice, IPAS was predominantly expressed in Purkinje cells of the cerebellum and in corneal epithelium of the eye. Expression of IPAS in the cornea correlates with low levels of expression of the VEGF gene under hypoxic conditions. Application of an IPAS antisense oligonucleotide to the mouse cornea induced angiogenesis under normal oxygen conditions, and demonstrated hypoxia-dependent induction of VEGF gene expression in hypoxic corneal cells. These results indicate a previously unknown mechanism for negative regulation of angiogenesis and maintenance of an avascular phenotype.

Negative regulation of parathyroid hormone-related protein expression by steroid hormones

International Nuclear Information System (INIS)

Kajitani, Takashi; Tamamori-Adachi, Mimi; Okinaga, Hiroko; Chikamori, Minoru; Iizuka, Masayoshi; Okazaki, Tomoki

2011-01-01

Highlights: → Steroid hormones repress expression of PTHrP in the cell lines where the corresponding nuclear receptors are expressed. → Nuclear receptors are required for suppression of PTHrP expression by steroid hormones, except for androgen receptor. → Androgen-induced suppression of PTHrP expression appears to be mediated by estrogen receptor. -- Abstract: Elevated parathyroid hormone-related protein (PTHrP) is responsible for humoral hypercalcemia of malignancy (HHM), which is of clinical significance in treatment of terminal patients with malignancies. Steroid hormones were known to cause suppression of PTHrP expression. However, detailed studies linking multiple steroid hormones to PTHrP expression are lacking. Here we studied PTHrP expression in response to steroid hormones in four cell lines with excessive PTHrP production. Our study established that steroid hormones negatively regulate PTHrP expression. Vitamin D receptor, estrogen receptor α, glucocorticoid receptor, and progesterone receptor, were required for repression of PTHrP expression by the cognate ligands. A notable exception was the androgen receptor, which was dispensable for suppression of PTHrP expression in androgen-treated cells. We propose a pathway(s) involving nuclear receptors to suppress PTHrP expression.

Using the Positive and Negative Syndrome Scale (PANSS) to Define Different Domains of Negative Symptoms: Prediction of Everyday Functioning by Impairments in Emotional Expression and Emotional Experience.

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Harvey, Philip D; Khan, Anzalee; Keefe, Richard S E

2017-12-01

Background: Reduced emotional experience and expression are two domains of negative symptoms. The authors assessed these two domains of negative symptoms using previously developed Positive and Negative Syndrome Scale (PANSS) factors. Using an existing dataset, the authors predicted three different elements of everyday functioning (social, vocational, and everyday activities) with these two factors, as well as with performance on measures of functional capacity. Methods: A large (n=630) sample of people with schizophrenia was used as the data source of this study. Using regression analyses, the authors predicted the three different aspects of everyday functioning, first with just the two Positive and Negative Syndrome Scale factors and then with a global negative symptom factor. Finally, we added neurocognitive performance and functional capacity as predictors. Results: The Positive and Negative Syndrome Scale reduced emotional experience factor accounted for 21 percent of the variance in everyday social functioning, while reduced emotional expression accounted for no variance. The total Positive and Negative Syndrome Scale negative symptom factor accounted for less variance (19%) than the reduced experience factor alone. The Positive and Negative Syndrome Scale expression factor accounted for, at most, one percent of the variance in any of the functional outcomes, with or without the addition of other predictors. Implications: Reduced emotional experience measured with the Positive and Negative Syndrome Scale, often referred to as "avolition and anhedonia," specifically predicted impairments in social outcomes. Further, reduced experience predicted social impairments better than emotional expression or the total Positive and Negative Syndrome Scale negative symptom factor. In this cross-sectional study, reduced emotional experience was specifically related with social outcomes, accounting for essentially no variance in work or everyday activities, and being the

Osteoprotegerin expression in triple-negative breast cancer cells promotes metastasis

International Nuclear Information System (INIS)

Weichhaus, Michael; Segaran, Prabu; Renaud, Ashleigh; Geerts, Dirk; Connelly, Linda

2014-01-01

Osteoprotegerin (OPG) is a secreted member of the tumor necrosis factor (TNF) receptor superfamily that has been well characterized as a negative regulator of bone remodeling. OPG is also expressed in human breast cancer tissues and cell lines. In vitro studies suggest that OPG exerts tumor-promoting effects by binding to TNF-related apoptosis inducing ligand (TRAIL), thereby preventing induction of apoptosis. However, the in vivo effect of OPG expression by primary breast tumors has not been characterized. We knocked down OPG expression in MDA-MB-231 and MDA-MB-436 human breast cancer cells using shRNA and siRNA to investigate impact on metastasis in the chick embryo model. We observed a reduction in metastasis with OPG knockdown cells. We found that lowering OPG expression did not alter sensitivity to TRAIL-induced apoptosis; however, the OPG knockdown cells had a reduced level of invasion. In association with this we observed reduced expression of the proteases Cathepsin D and Matrix Metalloproteinase-2 upon OPG knockdown, indicating that OPG may promote metastasis via modulation of protease expression and invasion. We conclude that OPG has a metastasis-promoting effect in breast cancer cells

Treatment with escitalopram improves the attentional bias toward negative facial expressions in patients with major depressive disorders.

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Zhou, Zhenhe; Cao, Suxia; Li, Hengfen; Li, Youhui

2015-10-01

We hypothesized that treatment with escitalopram would improve cognitive bias and contribute to the recovery process for patients with major depressive disorder (MDD). Many previous studies have established that patients with MDD tend to pay selective attention to negative stimuli. The assessment of the level of cognitive bias is regarded as a crucial dimension of treatment outcomes for MDD. To our knowledge, no prior studies have been reported on the effects of treatment with escitalopram on attentional bias in MDD, employing a dot probe task of facial expression. We studied 25 patients with MDD and 25 controls, and used a dot probe task of facial expression to measure cognitive bias. The patients' psychopathologies were rated using the Hamilton Depression Scale (HAMD) at baseline and after 8 weeks of treatment with escitalopram. All participants performed the facial expression dot probe task. The results revealed that the 8 week escitalopram treatment decreased the HAMD scores. The patients with MDD at baseline exhibited an attentional bias towards negative faces, however, no significant bias toward either negative or happy faces were observed in the controls. After the 8 week escitalopram treatment, no significant bias toward negative faces was observed in the patient group. In conclusion, patients with MDD pay more attention to negative facial expressions, and treatment with escitalopram improves this attentional bias toward negative facial expressions. This is the first study, to our knowledge, on the effects of treatment with escitalopram on attentional bias in patients with MDD that has employed a dot probe task of facial expression. Copyright © 2015 Elsevier Ltd. All rights reserved.

IL-8 expression and its possible relationship with estrogen-receptor-negative status of breast cancer cells

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Freund, Ariane; Chauveau, Corine; Brouillet, Jean-Paul; Lucas, Annick; Lacroix, Matthieu; Licznar, Anne; Vignon, Françoise; Lazennec, Gwendal

2003-01-01

Estrogen receptor (ER) status is an important parameter in breast cancer management as ER-positive breast cancers have a better prognosis than ER-negative tumors. This difference comes essentially from the lower aggressiveness and invasiveness of ER-positive tumors. Here, we demonstrate, that IL-8 was clearly overexpressed in most ER-negative breast, ovary cell lines and breast tumor samples tested, whereas no significant IL-8 level could be detected in ER-positive breast or ovarian cell lines. We have also cloned human IL-8 from ER-negative MDA-MB-231 cells and we show that IL-8 produced by breast cancer cells is identical to monocyte-derived IL-8. Interestingly, the invasion potential of ER-negative breast cancer cells is associated at least in part with expression of interleukin-8 (IL-8), but not with IL-8 receptors levels. Moreover, IL-8 increases the invasiveness of ER-positive breast cancer cells by 2 fold, thus confirming the invasion-promoting role of IL-8. On the other hand, exogenous expression of estrogen receptors in ER-negative cells led to a decrease of IL-8 levels. In summary, our data show that IL-8 expression is negatively linked to ER-status of breast and ovarian cancer cells. We also support the idea that IL-8 expression is associated with a higher invasiveness potential of cancer cells in vitro, which suggests that IL-8 could be a novel marker of tumor aggressiveness. PMID:12527894

Partial Least Squares Based Gene Expression Analysis in EBV- Positive and EBV-Negative Posttransplant Lymphoproliferative Disorders.

Science.gov (United States)

Wu, Sa; Zhang, Xin; Li, Zhi-Ming; Shi, Yan-Xia; Huang, Jia-Jia; Xia, Yi; Yang, Hang; Jiang, Wen-Qi

2013-01-01

Post-transplant lymphoproliferative disorder (PTLD) is a common complication of therapeutic immunosuppression after organ transplantation. Gene expression profile facilitates the identification of biological difference between Epstein-Barr virus (EBV) positive and negative PTLDs. Previous studies mainly implemented variance/regression analysis without considering unaccounted array specific factors. The aim of this study is to investigate the gene expression difference between EBV positive and negative PTLDs through partial least squares (PLS) based analysis. With a microarray data set from the Gene Expression Omnibus database, we performed PLS based analysis. We acquired 1188 differentially expressed genes. Pathway and Gene Ontology enrichment analysis identified significantly over-representation of dysregulated genes in immune response and cancer related biological processes. Network analysis identified three hub genes with degrees higher than 15, including CREBBP, ATXN1, and PML. Proteins encoded by CREBBP and PML have been reported to be interact with EBV before. Our findings shed light on expression distinction of EBV positive and negative PTLDs with the hope to offer theoretical support for future therapeutic study.

Role of NeuroD1 on the negative regulation of Pomc expression by glucocorticoid.

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Rehana Parvin

Full Text Available The mechanism of the negative regulation of proopiomelanocortin gene (Pomc by glucocorticoids (Gcs is still unclear in many points. Here, we demonstrated the involvement of neurogenic differentiation factor 1 (NeuroD1 in the Gc-mediated negative regulation of Pomc. Murine pituitary adrenocorticotropic hormone (ACTH producing corticotroph tumor-derived AtT20 cells were treated with dexamethasone (DEX (1-100 nM and cultured for 24 hrs. Thereafter, Pomc mRNA expression was studied by quantitative real-time PCR and rat Pomc promoter (-703/+58 activity was examined by luciferase assay. Both Pomc mRNA expression and Pomc promoter activity were inhibited by DEX in a dose-dependent manner. Deletion and point mutant analyses of Pomc promoter suggested that the DEX-mediated transcriptional repression was mediated via E-box that exists at -376/-371 in the promoter. Since NeuroD1 is known to bind to and activate E-box of the Pomc promoter, we next examined the effect of DEX on NeuroD1 expression. Interestingly, DEX dose-dependently inhibited NeuroD1 mRNA expression, mouse NeuroD1 promoter (-2.2-kb activity, and NeuroD1 protein expression in AtT20 cells. In addition, we confirmed the inhibitory effect of DEX on the interaction of NeuroD1 and E-box on Pomc promoter by chromatin immunoprecipitation (ChIP assay. Finally, overexpression of mouse NeuroD1 could rescue the DEX-mediated inhibition of Pomc mRNA expression and Pomc promoter activity. Taken together, it is suggested that the suppression of NeuroD1 expression and the inhibition of NeuroD1/E-box interaction may play an important role in the Gc-mediated negative regulation of Pomc.

Gene expression variation to predict 10-year survival in lymph-node-negative breast cancer

International Nuclear Information System (INIS)

Karlsson, Elin; Delle, Ulla; Danielsson, Anna; Olsson, Björn; Abel, Frida; Karlsson, Per; Helou, Khalil

2008-01-01

It is of great significance to find better markers to correctly distinguish between high-risk and low-risk breast cancer patients since the majority of breast cancer cases are at present being overtreated. 46 tumours from node-negative breast cancer patients were studied with gene expression microarrays. A t-test was carried out in order to find a set of genes where the expression might predict clinical outcome. Two classifiers were used for evaluation of the gene lists, a correlation-based classifier and a Voting Features Interval (VFI) classifier. We then evaluated the predictive accuracy of this expression signature on tumour sets from two similar studies on lymph-node negative patients. They had both developed gene expression signatures superior to current methods in classifying node-negative breast tumours. These two signatures were also tested on our material. A list of 51 genes whose expression profiles could predict clinical outcome with high accuracy in our material (96% or 89% accuracy in cross-validation, depending on type of classifier) was developed. When tested on two independent data sets, the expression signature based on the 51 identified genes had good predictive qualities in one of the data sets (74% accuracy), whereas their predictive value on the other data set were poor, presumably due to the fact that only 23 of the 51 genes were found in that material. We also found that previously developed expression signatures could predict clinical outcome well to moderately well in our material (72% and 61%, respectively). The list of 51 genes derived in this study might have potential for clinical utility as a prognostic gene set, and may include candidate genes of potential relevance for clinical outcome in breast cancer. According to the predictions by this expression signature, 30 of the 46 patients may have benefited from different adjuvant treatment than they recieved. The research on these tumours was approved by the Medical Faculty Research

Branched-Chain Amino Acid Negatively Regulates KLF15 Expression via PI3K-AKT Pathway.

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Liu, Yunxia; Dong, Weibing; Shao, Jing; Wang, Yibin; Zhou, Meiyi; Sun, Haipeng

2017-01-01

Recent studies have linked branched-chain amino acid (BCAA) with numerous metabolic diseases. However, the molecular basis of BCAA's roles in metabolic regulation remains to be established. KLF15 (Krüppel-like factor 15) is a transcription factor and master regulator of glycemic, lipid, and amino acids metabolism. In the present study, we found high concentrations of BCAA suppressed KLF15 expression while BCAA starvation induced KLF15 expression, suggesting KLF15 expression is negatively controlled by BCAA.Interestingly, BCAA starvation induced PI3K-AKT signaling. KLF15 induction by BCAA starvation was blocked by PI3K and AKT inhibitors, indicating the activation of PI3K-AKT signaling pathway mediated the KLF15 induction. BCAA regulated KLF15 expression at transcriptional level but not post-transcriptional level. However, BCAA starvation failed to increase the KLF15-promoter-driven luciferase expression, suggesting KLF15 promoter activity was not directly controlled by BCAA. Finally, fasting reduced BCAA abundance in mice and KLF15 expression was dramatically induced in muscle and white adipose tissue, but not in liver. Together, these data demonstrated BCAA negatively regulated KLF15 expression, suggesting a novel molecular mechanism underlying BCAA's multiple functions in metabolic regulation.

Branched-Chain Amino Acid Negatively Regulates KLF15 Expression via PI3K-AKT Pathway

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Yunxia Liu

2017-10-01

Full Text Available Recent studies have linked branched-chain amino acid (BCAA with numerous metabolic diseases. However, the molecular basis of BCAA's roles in metabolic regulation remains to be established. KLF15 (Krüppel-like factor 15 is a transcription factor and master regulator of glycemic, lipid, and amino acids metabolism. In the present study, we found high concentrations of BCAA suppressed KLF15 expression while BCAA starvation induced KLF15 expression, suggesting KLF15 expression is negatively controlled by BCAA.Interestingly, BCAA starvation induced PI3K-AKT signaling. KLF15 induction by BCAA starvation was blocked by PI3K and AKT inhibitors, indicating the activation of PI3K-AKT signaling pathway mediated the KLF15 induction. BCAA regulated KLF15 expression at transcriptional level but not post-transcriptional level. However, BCAA starvation failed to increase the KLF15-promoter-driven luciferase expression, suggesting KLF15 promoter activity was not directly controlled by BCAA. Finally, fasting reduced BCAA abundance in mice and KLF15 expression was dramatically induced in muscle and white adipose tissue, but not in liver. Together, these data demonstrated BCAA negatively regulated KLF15 expression, suggesting a novel molecular mechanism underlying BCAA's multiple functions in metabolic regulation.

Monitoring of regulatory T cell frequencies and expression of CTLA-4 on T cells, before and after DC vaccination, can predict survival in GBM patients.

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Brendan Fong

Full Text Available PURPOSE: Dendritic cell (DC vaccines have recently emerged as an innovative therapeutic option for glioblastoma patients. To identify novel surrogates of anti-tumor immune responsiveness, we studied the dynamic expression of activation and inhibitory markers on peripheral blood lymphocyte (PBL subsets in glioblastoma patients treated with DC vaccination at UCLA. EXPERIMENTAL DESIGN: Pre-treatment and post-treatment PBL from 24 patients enrolled in two Phase I clinical trials of dendritic cell immunotherapy were stained and analyzed using flow cytometry. A univariate Cox proportional hazards model was utilized to investigate the association between continuous immune monitoring variables and survival. Finally, the immune monitoring variables were dichotomized and a recursive partitioning survival tree was built to obtain cut-off values predictive of survival. RESULTS: The change in regulatory T cell (CD3(+CD4(+CD25(+CD127(low frequency in PBL was significantly associated with survival (p = 0.0228; hazard ratio = 3.623 after DC vaccination. Furthermore, the dynamic expression of the negative co-stimulatory molecule, CTLA-4, was also significantly associated with survival on CD3(+CD4(+ T cells (p = 0.0191; hazard ratio = 2.840 and CD3(+CD8(+ T cells (p = 0.0273; hazard ratio = 2.690, while that of activation markers (CD25, CD69 was not. Finally, a recursive partitioning tree algorithm was utilized to dichotomize the post/pre fold change immune monitoring variables. The resultant cut-off values from these immune monitoring variables could effectively segregate these patients into groups with significantly different overall survival curves. CONCLUSIONS: Our results suggest that monitoring the change in regulatory T cell frequencies and dynamic expression of the negative co-stimulatory molecules on peripheral blood T cells, before and after DC vaccination, may predict survival. The cut-off point generated from these data can be utilized in future

Do Infants Show Distinct Negative Facial Expressions for Fear and Anger? Emotional Expression in 11-Month-Old European American, Chinese, and Japanese Infants

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Camras, Linda A.; Oster, Harriet; Bakeman, Roger; Meng, Zhaolan; Ujiie, Tatsuo; Campos, Joseph J.

2007-01-01

Do infants show distinct negative facial expressions for different negative emotions? To address this question, European American, Chinese, and Japanese 11-month-olds were videotaped during procedures designed to elicit mild anger or frustration and fear. Facial behavior was coded using Baby FACS, an anatomically based scoring system. Infants'…

Hessian regularization based non-negative matrix factorization for gene expression data clustering.

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Liu, Xiao; Shi, Jun; Wang, Congzhi

2015-01-01

Since a key step in the analysis of gene expression data is to detect groups of genes that have similar expression patterns, clustering technique is then commonly used to analyze gene expression data. Data representation plays an important role in clustering analysis. The non-negative matrix factorization (NMF) is a widely used data representation method with great success in machine learning. Although the traditional manifold regularization method, Laplacian regularization (LR), can improve the performance of NMF, LR still suffers from the problem of its weak extrapolating power. Hessian regularization (HR) is a newly developed manifold regularization method, whose natural properties make it more extrapolating, especially for small sample data. In this work, we propose the HR-based NMF (HR-NMF) algorithm, and then apply it to represent gene expression data for further clustering task. The clustering experiments are conducted on five commonly used gene datasets, and the results indicate that the proposed HR-NMF outperforms LR-based NMM and original NMF, which suggests the potential application of HR-NMF for gene expression data.

Amygdala and fusiform gyrus temporal dynamics: Responses to negative facial expressions

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Rauch Scott L

2008-05-01

Full Text Available Abstract Background The amygdala habituates in response to repeated human facial expressions; however, it is unclear whether this brain region habituates to schematic faces (i.e., simple line drawings or caricatures of faces. Using an fMRI block design, 16 healthy participants passively viewed repeated presentations of schematic and human neutral and negative facial expressions. Percent signal changes within anatomic regions-of-interest (amygdala and fusiform gyrus were calculated to examine the temporal dynamics of neural response and any response differences based on face type. Results The amygdala and fusiform gyrus had a within-run "U" response pattern of activity to facial expression blocks. The initial block within each run elicited the greatest activation (relative to baseline and the final block elicited greater activation than the preceding block. No significant differences between schematic and human faces were detected in the amygdala or fusiform gyrus. Conclusion The "U" pattern of response in the amygdala and fusiform gyrus to facial expressions suggests an initial orienting, habituation, and activation recovery in these regions. Furthermore, this study is the first to directly compare brain responses to schematic and human facial expressions, and the similarity in brain responses suggest that schematic faces may be useful in studying amygdala activation.

Branched-Chain Amino Acid Negatively Regulates KLF15 Expression via PI3K-AKT Pathway

OpenAIRE

Yunxia Liu; Weibing Dong; Jing Shao; Yibin Wang; Meiyi Zhou; Haipeng Sun

2017-01-01

Recent studies have linked branched-chain amino acid (BCAA) with numerous metabolic diseases. However, the molecular basis of BCAA's roles in metabolic regulation remains to be established. KLF15 (Krüppel-like factor 15) is a transcription factor and master regulator of glycemic, lipid, and amino acids metabolism. In the present study, we found high concentrations of BCAA suppressed KLF15 expression while BCAA starvation induced KLF15 expression, suggesting KLF15 expression is negatively cont...

Automatic Change Detection to Facial Expressions in Adolescents: Evidence from Visual Mismatch Negativity Responses

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Tongran eLiu

2016-03-01

Full Text Available Adolescence is a critical period for the neurodevelopment of social-emotional processing, wherein the automatic detection of changes in facial expressions is crucial for the development of interpersonal communication. Two groups of participants (an adolescent group and an adult group were recruited to complete an emotional oddball task featuring on happy and one fearful condition. The measurement of event-related potential (ERP was carried out via electroencephalography (EEG and electrooculography (EOG recording, to detect visual mismatch negativity (vMMN with regard to the automatic detection of changes in facial expressions between the two age groups. The current findings demonstrated that the adolescent group featured more negative vMMN amplitudes than the adult group in the fronto-central region during the 120-200 ms interval. During the time window of 370-450 ms, only the adult group showed better automatic processing on fearful faces than happy faces. The present study indicated that adolescents posses stronger automatic detection of changes in emotional expression relative to adults, and sheds light on the neurodevelopment of automatic processes concerning social-emotional information.

Integrating and differentiating aspects of self-regulation: effortful control, executive functioning, and links to negative affectivity.

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Bridgett, David J; Oddi, Kate B; Laake, Lauren M; Murdock, Kyle W; Bachmann, Melissa N

2013-02-01

Subdisciplines within psychology frequently examine self-regulation from different frameworks despite conceptually similar definitions of constructs. In the current study, similarities and differences between effortful control, based on the psychobiological model of temperament (Rothbart, Derryberry, & Posner, 1994), and executive functioning are examined and empirically tested in three studies (n = 509). Structural equation modeling indicated that effortful control and executive functioning are strongly associated and overlapping constructs (Study 1). Additionally, results indicated that effortful control is related to the executive function of updating/monitoring information in working memory, but not inhibition (Studies 2 and 3). Study 3 also demonstrates that better updating/monitoring information in working memory and better effortful control were uniquely linked to lower dispositional negative affect, whereas the executive function of low/poor inhibition was uniquely associated with an increased tendency to express negative affect. Furthermore, dispositional negative affect mediated the links between effortful control and, separately, the executive function of updating/monitoring information in working memory and the tendency to express negative affect. The theoretical implications of these findings are discussed, and a potential framework for guiding future work directed at integrating and differentiating aspects of self-regulation is suggested. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Functional imaging: monitoring heme oxygenase-1 gene expression in vivo

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Zhang, Weisheng; Reilly-Contag, Pamela; Stevenson, David K.; Contag, Christopher H.

1999-07-01

The regulation of genetic elements can be monitored in living animals using photoproteins as reporters. Heme oxygenase (HO) is the key catabolic enzyme in the heme degradation pathway. Here, HO expression serves as a model for in vivo functional imaging of transcriptional regulation of a clinically relevant gene. HO enzymatic activity is inhibited by heme analogs, metalloporphyrins, but many members of this family of compounds also activate transcription of the HO-1 promoter. The degree of transcriptional activation by twelve metalloporphyrins, differing at the central metal and porphyrin ring substituents, was evaluated in both NIH 3T3 stable lines and transgenic animals containing HO-1 promoter-luciferase gene fusions. In the correlative cell culture assays, the metalloporphyrins increased transcription form the full length HO promoter fusion to varying degrees, but none increased transcription from a truncated HO-1 promoter. These results suggested that one or both of the two distal enhancer elements located at -4 and -10 Kb upstream from transcriptional start are required for HO-1 induction by heme and its analogs. The full-length HO-1-luc fusion was then evaluated as a transgene in mice. It was possible to monitor the effects of the metalloporphyrins, SnMP and ZnPP, in living animals over time. This spatiotemporal analyses of gene expression in vivo implied that alterations in porphyrin ring substituents and the central metal may affect the extent of gene activation. These data further indicate that using photoprotein reporters, subtle differences in gene expression can be monitored in living animals.

Using the Positive and Negative Syndrome Scale (PANSS) to Define Different Domains of Negative Symptoms: Prediction of Everyday Functioning by Impairments in Emotional Expression and Emotional Experience

OpenAIRE

Harvey, Philip D.; Khan, Anzalee; Keefe, Richard S. E.

2017-01-01

Background: Reduced emotional experience and expression are two domains of negative symptoms. The authors assessed these two domains of negative symptoms using previously developed Positive and Negative Syndrome Scale (PANSS) factors. Using an existing dataset, the authors predicted three different elements of everyday functioning (social, vocational, and everyday activities) with these two factors, as well as with performance on measures of functional capacity. Methods: A large (n=630) sampl...

The prognostic value of Her4 receptor isoform expression in triple-negative and Her2 positive breast cancer patients

International Nuclear Information System (INIS)

Machleidt, Anna; Buchholz, Stefan; Diermeier-Daucher, Simone; Zeman, Florian; Ortmann, Olaf; Brockhoff, Gero

2013-01-01

Not only four but rather seven different human epidermal growth factor receptor related (Her) receptor tyrosine kinases (RTKs) have been described to be expressed in a variety of normal and neoplastic tissues: Her1, Her2, Her3, and additionally four Her4 isoforms have been identified. A differential expression of Her4 isoforms does not, however, play any role in either the molecular diagnostics or treatment decision for breast cancer patients. The prognostic and predictive impact of Her4 expression in breast cancer is basically unclear. We quantified the Her4 variants JM-a/CYT1, JM-a/CYT2, JM-b/CYT1, and JM-b/CYT2 by isoform-specific polymerase chain reaction (qPCR) in (i) triple-negative, (ii) Her2 positive breast cancer tissues and (iii) in benign breast tissues. In all three tissue collectives we never found the JM-b/CYT1 or the JM-b/CYT2 isoform expressed. In contrast, the two JM-a/CYT1 and JM-a/CYT2 isoforms were always simultaneously expressed but at different ratios. We identified a positive prognostic impact on overall survival (OS) in triple-negative and event-free survival (EFS) in Her2 positive patients. This finding is independent of the absolute JM-a/CYT1 to JM-a/CYT2 expression ratio. In Her2 positive patients, Her4 expression only has a favorable effect in estrogen-receptor (ER)-positive but not in ER-negative individuals. In summary, JM-a/CYT1 and JM-a/CYT2 but not JM-b isoforms of the Her4 receptor are simultaneously expressed in both triple-negative and Her2 positive breast cancer tissues. Although different expression ratios of the two JM-a isoforms did not reveal any additional information, Her4 expression basically indicates a prolonged EFS and OFS. An extended expression analysis that takes all Her receptor homologs, including the Her4 isoforms, into account might render more precisely the molecular diagnostics required for the development of optimized targeted therapies

Heterogeneity of triple-negative breast cancer: mammographic, US, and MR imaging features according to androgen receptor expression

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Bae, Min Sun; Song, Sung Eun; Kim, Won Hwa; Lee, Su Hyun; Moon, Woo Kyung [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Park, So Yeon; Park, In-Ae [Seoul National University College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Han, Wonshik; Noh, Dong-Young [Seoul National University College of Medicine, Department of Surgery, Seoul (Korea, Republic of)

2014-09-16

Our aim was to determine whether triple-negative breast cancers (TNBCs) with and without androgen receptor (AR) expression have distinguishing imaging features on mammography, breast ultrasound (US), and magnetic resonance (MR) imaging. AR expression was assessed immunohistochemically in 125 patients with TNBC from a consecutive series of 1,086 operable invasive breast cancers. Two experienced radiologists blinded to clinicopathological findings reviewed all imaging studies in consensus using the BI-RADS lexicon. The imaging and pathological features of 33 AR-positive TNBCs were compared with those of 92 AR-negative TNBCs. The presence of mammographic calcifications with or without a mass (p < 0.001), non-mass enhancement on MR imaging (p < 0.001), and masses with irregular shape or spiculated margins on US (p < 0.001 and p = 0.002) and MR imaging (p = 0.001 and p < 0.001) were significantly associated with AR-positive TNBC. Compared with AR-negative TNBC, AR-positive TNBC was more likely to have a ductal carcinoma in situ component (59.8 % vs. 90.9 %, p = 0.001) and low Ki-67 expression (30.4 % vs. 51.5 %, p = 0.030). AR-positive and AR-negative TNBCs have different imaging features, and certain imaging findings can be useful to predict AR status in TNBC. (orig.)

Negative Facial Expressions - But Not Visual Scenes - Enhance Human Working Memory in Younger and Older Participants.

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Belham, Flávia Schechtman; Tavares, Maria Clotilde H; Satler, Corina; Garcia, Ana; Rodrigues, Rosângela C; Canabarro, Soraya L de Sá; Tomaz, Carlos

2017-01-01

Many studies have investigated the influence of emotion on memory processes across the human lifespan. Some results have shown older adults (OA) performing better with positive stimuli, some with negative items, whereas some found no impact of emotional valence. Here we tested, in two independent studies, how younger adults (YA) and OA would perform in a visuospatial working memory (VSWM) task with positive, negative, and neutral images. The task consisted of identifying the new location of a stimulus in a crescent set of identical stimuli presented in different locations in a touch-screen monitor. In other words, participants should memorize the locations previously occupied to identify the new location. For each trial, the number of occupied locations increased until 8 or until a mistake was made. In study 1, 56 YA and 38 OA completed the task using images from the International Affective Picture System (IAPS). Results showed that, although YA outperformed OA, no effects of emotion were found. In study 2, 26 YA and 25 OA were tested using facial expressions as stimuli. Data from this study showed that negative faces facilitated performance and this effect did not differ between age groups. No differences were found between men and women. Taken together, our findings suggest that YA and OA's VSWM can be influenced by the emotional valence of the information, though this effect was present only for facial stimuli. Presumably, this may have happened due to the social and biological importance of such stimuli, which are more effective in transmitting emotions than IAPS images. Critically, our results also indicate that the mixed findings in the literature about the influence of aging on the interactions between memory and emotion may be caused by the use of different stimuli and methods. This possibility should be kept in mind in future studies about memory and emotion across the lifespan.

Quorum sensing in gram-negative bacteria

DEFF Research Database (Denmark)

Wu, H.; Song, Z.J.; Høiby, N.

2004-01-01

Bacteria can communicate with each other by means of signal molecules to coordinate the behavior of the entire community, and the mechanism is referred to as quorum sensing (QS). Signal systems enable bacteria to sense the size of their densities by monitoring the concentration of the signal...... molecules. Among Gram-negative bacteria N-acyl-L-homoserine lactone (acyl-HSL)-dependent quorum sensing systems are particularly widespread. These systems are used to coordinate expression of phenotypes that are fundamental to the interaction of bacteria with each other and with their environment...

Negative argininosuccinate synthetase expression in melanoma tumours may predict clinical benefit from arginine-depleting therapy with pegylated arginine deiminase

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Feun, L G; Marini, A; Walker, G; Elgart, G; Moffat, F; Rodgers, S E; Wu, C J; You, M; Wangpaichitr, M; Kuo, M T; Sisson, W; Jungbluth, A A; Bomalaski, J; Savaraj, N

2012-01-01

Background: Arginine-depleting therapy with pegylated arginine deiminase (ADI-PEG20) was reported to have activity in advanced melanoma in early phase I–II trial, and clinical trials are currently underway in other cancers. However, the optimal patient population who benefit from this treatment is unknown. Methods: Advanced melanoma patients with accessible tumours had biopsy performed before the start of treatment with ADI-PEG20 and at the time of progression or relapse when amenable to determine whether argininosuccinate synthetase (ASS) expression in tumour was predictive of response to ADI-PEG20. Results: Twenty-seven of thirty-eight patients treated had melanoma tumours assessable for ASS staining before treatment. Clinical benefit rate (CBR) and longer time to progression were associated with negative expression of tumour ASS. Only 1 of 10 patients with ASS-positive tumours (ASS+) had stable disease, whereas 4 of 17 (24%) had partial response and 5 had stable disease, when ASS expression was negative (ASS−), giving CBR rates of 52.9 vs 10%, P=0.041. Two responding patients with negative ASS expression before therapy had rebiopsy after tumour progression and the ASS expression became positive. The survival of ASS− patients receiving at least four doses at 320 IU m−2 was significantly better than the ASS+ group at 26.5 vs 8.5 months, P=0.024. Conclusion: ADI-PEG20 is safe and the drug is only efficacious in melanoma patients whose tumour has negative ASS expression. Argininosuccinate synthetase tumour positivity is associated with drug resistance and tumour progression. PMID:22472884

The late posterior negativity in ERP studies of episodic memory: action monitoring and retrieval of attribute conjunctions.

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Johansson, Mikael; Mecklinger, Axel

2003-10-01

The focus of the present paper is a late posterior negative slow wave (LPN) that has frequently been reported in event-related potential (ERP) studies of memory. An overview of these studies suggests that two broad classes of experimental conditions tend to elicit this component: (a) item recognition tasks associated with enhanced action monitoring demands arising from response conflict and (b) memory tasks that require the binding of items with contextual information specifying the study episode. A combined stimulus- and response-locked analysis of data from two studies mapping onto these classes allowed a temporal and functional decomposition of the LPN. While only the LPN observed in the item recognition task could be attributed to the involvement of a posteriorly distributed response-locked error-related negativity (or error negativity; ERN/Ne) occurring immediately after the response, the source-memory task was associated with a stimulus-locked negative slow wave occurring prior and during response execution that was evident when data were matched for response latencies. We argue that the presence of the former reflects action monitoring due to high levels of response conflict, whereas the latter reflects retrieval processes that may act to reconstruct the prior study episode when task-relevant attribute conjunctions are not readily recovered or need continued evaluation.

Both positive and negative regulatory elements mediate expression of a photoregulated CAB gene from Nicotiana plumbaginifolia.

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Castresana, C; Garcia-Luque, I; Alonso, E; Malik, V S; Cashmore, A R

1988-01-01

We have analyzed promoter regulatory elements from a photoregulated CAB gene (Cab-E) isolated from Nicotiana plumbaginifolia. These studies have been performed by introducing chimeric gene constructs into tobacco cells via Agrobacterium tumefaciens-mediated transformation. Expression studies on the regenerated transgenic plants have allowed us to characterize three positive and one negative cis-acting elements that influence photoregulated expression of the Cab-E gene. Within the upstream sequences we have identified two positive regulatory elements (PRE1 and PRE2) which confer maximum levels of photoregulated expression. These sequences contain multiple repeated elements related to the sequence-ACCGGCCCACTT-. We have also identified within the upstream region a negative regulatory element (NRE) extremely rich in AT sequences, which reduces the level of gene expression in the light. We have defined a light regulatory element (LRE) within the promoter region extending from -396 to -186 bp which confers photoregulated expression when fused to a constitutive nopaline synthase ('nos') promoter. Within this region there is a 132-bp element, extending from -368 to -234 bp, which on deletion from the Cab-E promoter reduces gene expression from high levels to undetectable levels. Finally, we have demonstrated for a full length Cab-E promoter conferring high levels of photoregulated expression, that sequences proximal to the Cab-E TATA box are not replaceable by corresponding sequences from a 'nos' promoter. This contrasts with the apparent equivalence of these Cab-E and 'nos' TATA box-proximal sequences in truncated promoters conferring low levels of photoregulated expression. Images PMID:2901343

Do negative emotions expressed during follow-up consultations with adolescent survivors of childhood cancer reflect late effects?

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Mellblom, Anneli V; Ruud, Ellen; Loge, Jon Håvard; Lie, Hanne C

2017-11-01

To explore whether negative emotions expressed by adolescent cancer survivors during follow-up consultations were associated with potential late effects (persisting disease or treatment-related health problems). We video-recorded 66 follow-up consultations between 10 pediatricians and 66 adolescent survivors of leukemia, lymphoma or stem-cell transplantations. In transcripts of the recordings, we identified utterances coded as both 1) expressions of negative emotions (VR-CoDES), and 2) late effect-related discussions. Principles of thematic content analysis were used to investigate associations between the two. Of the 66 video-recorded consultations, 22 consultations contained 56 (49%) utterances coded as both emotional concerns and discussions of potential late effects. Negative emotions were most commonly associated with late effects such as fatigue ("I'm struggling with not having energy"), psychosocial distress ("When I touch this (scar) I become nauseous"), pain ("I'm wondering how long I am going to have this pain?"), and treatment-related effects on physical appearance ("Am I growing?"). Negative emotions expressed by adolescent cancer survivors during follow-up consultations were frequently associated with potential late effects. These late effects were not the medically most serious ones, but reflected issues affecting the adolescents' daily life. Eliciting and exploring patients' emotional concerns serve as means to obtain clinically relevant information regarding potential late effect and to provide emotional support. Copyright © 2017 Elsevier B.V. All rights reserved.

Teachers' Negative Experiences and Expressions of Emotion: Being True to Yourself or Keeping You in Your Place?

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Kitching, Karl

2009-01-01

This paper examines teachers' experiences and displays of negative emotion as a means of partially exploring how identities at work might be formed and regulated. It uses the concepts of emotional labour and subjectivation to interrogate the negative emotions teachers may experience and/or express at work. It suggests that emotion display rules…

Expression levels of matrix metalloproteinase-9 and gram-negative bacteria in symptomatic and asymptomatic periapical lesions.

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Ahmed, Geraldine M; El-Baz, Alaa A; Hashem, Ahmed Abdel Rahman; Shalaan, Abeer K

2013-04-01

The aim of this study was to test the hypothesis that the expression of matrix metalloproteinase (MMP)-9 is significantly elevated in patients with symptomatic apical periodontitis and to correlate this with the detected amount of gram-negative bacteria. Twenty-six patients with periapical lesions involving at least 2 teeth were included in this study. The patients were divided into 2 groups: the symptomatic (SYM) group included 13 patients expressing pain with periapical lesions, and the asymptomatic (ASYM) group included 13 patients expressing no pain. Root canal treatment was performed followed by endodontic surgery and periapical lesion collection. Periapical lesions were serially cut into 4-μ sections. Some sections were processed for histologic examination using hematoxylin-eosin stain. Other sections were processed for immunohistochemical examination. For MMP-9, the area fraction of the positive cells was measured, and the percentage of the MMP-9-immunopositive area to the total area of the microscopic field was calculated. For gram-negative stain cells, the number of cells showing the pink-red color was counted per microscopic field. The Student's t test was used to compare the SYM and ASYM groups. The Pearson correlation coefficient was used to determine a significant correlation between the number of cells and the MMP-9 level. The significance level was set at P ≤ .05. The SYM group showed a statistically significantly higher mean number of gram-negative cells (P = .001) and MMP-9 area percent (P < .001) than the ASYM group. There was a statistically significant positive (r = .927) correlation between the number of gram-negative cells and the MMP-9 area percent (P< .001). There is good evidence to suspect a significant role of gram-negative bacteria and MMP-9 in symptomatic periapical lesions. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Brain negativity as an indicator of predictive error processing: the contribution of visual action effect monitoring.

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Joch, Michael; Hegele, Mathias; Maurer, Heiko; Müller, Hermann; Maurer, Lisa Katharina

2017-07-01

The error (related) negativity (Ne/ERN) is an event-related potential in the electroencephalogram (EEG) correlating with error processing. Its conditions of appearance before terminal external error information suggest that the Ne/ERN is indicative of predictive processes in the evaluation of errors. The aim of the present study was to specifically examine the Ne/ERN in a complex motor task and to particularly rule out other explaining sources of the Ne/ERN aside from error prediction processes. To this end, we focused on the dependency of the Ne/ERN on visual monitoring about the action outcome after movement termination but before result feedback (action effect monitoring). Participants performed a semi-virtual throwing task by using a manipulandum to throw a virtual ball displayed on a computer screen to hit a target object. Visual feedback about the ball flying to the target was masked to prevent action effect monitoring. Participants received a static feedback about the action outcome (850 ms) after each trial. We found a significant negative deflection in the average EEG curves of the error trials peaking at ~250 ms after ball release, i.e., before error feedback. Furthermore, this Ne/ERN signal did not depend on visual ball-flight monitoring after release. We conclude that the Ne/ERN has the potential to indicate error prediction in motor tasks and that it exists even in the absence of action effect monitoring. NEW & NOTEWORTHY In this study, we are separating different kinds of possible contributors to an electroencephalogram (EEG) error correlate (Ne/ERN) in a throwing task. We tested the influence of action effect monitoring on the Ne/ERN amplitude in the EEG. We used a task that allows us to restrict movement correction and action effect monitoring and to control the onset of result feedback. We ascribe the Ne/ERN to predictive error processing where a conscious feeling of failure is not a prerequisite. Copyright © 2017 the American Physiological

Expression of aurora kinase A is associated with metastasis-free survival in node-negative breast cancer patients

Directory of Open Access Journals (Sweden)

Siggelkow Wulf

2012-11-01

Full Text Available Abstract Background Inhibitors targeting the cell cycle-regulated aurora kinase A (AURKA are currently being developed. Here, we examine the prognostic impact of AURKA in node-negative breast cancer patients without adjuvant systemic therapy (n = 766. Methods AURKA was analyzed using microarray-based gene-expression data from three independent cohorts of node-negative breast cancer patients. In multivariate Cox analyses, the prognostic impact of age, histological grade, tumor size, estrogen receptor (ER, and HER2 were considered. Results Patients with higher AURKA expression had a shorter metastasis-free survival (MFS in the Mainz (HR 1.93; 95% CI 1.34 – 2.78; P Conclusions AURKA is associated with worse prognosis in estrogen receptor positive breast carcinomas. Patients with the highest AURKA expression (>75% percentile have a particularly bad prognosis and may profit from therapy with AURKA inhibitors.

Why should I talk about emotion? Communication patterns associated with physician discussion of patient expressions of negative emotion in hospital admission encounters.

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Adams, Kristen; Cimino, Jenica E W; Arnold, Robert M; Anderson, Wendy G

2012-10-01

To describe hospital-based physicians' responses to patients' verbal expressions of negative emotion and identify patterns of further communication associated with different responses. Qualitative analysis of physician-patient admission encounters audio-recorded between August 2008 and March 2009 at two hospitals within a university system. A codebook was iteratively developed to identify patients' verbal expressions of negative emotion. We categorized physicians' responses by their immediate effect on further discussion of emotion - focused away (away), focused neither toward nor away (neutral), and focused toward (toward) - and examined further communication patterns following each response type. In 79 patients' encounters with 27 physicians, the median expression of negative emotion was 1, range 0-14. Physician responses were 25% away, 43% neutral, and 32% toward. Neutral and toward responses elicited patient perspectives, concerns, social and spiritual issues, and goals for care. Toward responses demonstrated physicians' support, contributing to physician-patient alignment and agreement about treatment. Responding to expressions of negative emotion neutrally or with statements that focus toward emotion elicits clinically relevant information and is associated with positive physician-patient relationship and care outcomes. Providers should respond to expressions of negative emotion with statements that allow for or explicitly encourage further discussion of emotion. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Sustained Expression of Negative Regulators of Myelination Protects Schwann Cells from Dysmyelination in a Charcot-Marie-Tooth 1B Mouse Model.

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Florio, Francesca; Ferri, Cinzia; Scapin, Cristina; Feltri, M Laura; Wrabetz, Lawrence; D'Antonio, Maurizio

2018-05-02

Schwann cell differentiation and myelination in the PNS are the result of fine-tuning of positive and negative transcriptional regulators. As myelination starts, negative regulators are downregulated, whereas positive ones are upregulated. Fully differentiated Schwann cells maintain an extraordinary plasticity and can transdifferentiate into "repair" Schwann cells after nerve injury. Reactivation of negative regulators of myelination is essential to generate repair Schwann cells. Negative regulators have also been implicated in demyelinating neuropathies, although their role in disease remains elusive. Here, we used a mouse model of Charcot-Marie-Tooth neuropathy type 1B (CMT1B), the P0S63del mouse characterized by ER stress and the activation of the unfolded protein response, to show that adult Schwann cells are in a partial differentiation state because they overexpress transcription factors that are normally expressed only before myelination. We provide evidence that two of these factors, Sox2 and Id2, act as negative regulators of myelination in vivo However, their sustained expression in neuropathy is protective because ablation of Sox2 or/and Id2 from S63del mice of both sexes results in worsening of the dysmyelinating phenotype. This is accompanied by increased levels of mutant P0 expression and exacerbation of ER stress, suggesting that limited differentiation may represent a novel adaptive mechanism through which Schwann cells counter the toxic effect of a mutant terminal differentiation protein. SIGNIFICANCE STATEMENT In many neuropathies, Schwann cells express high levels of early differentiation genes, but the significance of these altered expression remained unclear. Because many of these factors may act as negative regulators of myelination, it was suggested that their misexpression could contribute to dysmyelination. Here, we show that the transcription factors Sox2 and Id2 act as negative regulators of myelination in vivo , but that their sustained

Development of the work function monitoring method for a converter of a negative ion source

International Nuclear Information System (INIS)

Yamaoka, Hitoshi; Sasao, Mamiko; Wada, Motoi; Ramos, H.J.

1988-07-01

A method to monitor the change in the work function of the converter surface in a self-extraction negative ion source is developed. The photoelectron emission from the Cs-Mo surface in a plasma is detected by irradiating surface with laser lights. Negative ions produced at the surface shows a strong correlation with the photoelectron current from the surface in hydrogen and helium discharges. The photoelectron current induced by the Ar + laser is used to detect the change in the cesium coverage, or the work function, while that by the dye laser is found to be suitable to confirm the region of the work function minimum. (author)

Mothers' pupillary responses to infant facial expressions.

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Yrttiaho, Santeri; Niehaus, Dana; Thomas, Eileen; Leppänen, Jukka M

2017-02-06

Human parental care relies heavily on the ability to monitor and respond to a child's affective states. The current study examined pupil diameter as a potential physiological index of mothers' affective response to infant facial expressions. Pupillary time-series were measured from 86 mothers of young infants in response to an array of photographic infant faces falling into four emotive categories based on valence (positive vs. negative) and arousal (mild vs. strong). Pupil dilation was highly sensitive to the valence of facial expressions, being larger for negative vs. positive facial expressions. A separate control experiment with luminance-matched non-face stimuli indicated that the valence effect was specific to facial expressions and cannot be explained by luminance confounds. Pupil response was not sensitive to the arousal level of facial expressions. The results show the feasibility of using pupil diameter as a marker of mothers' affective responses to ecologically valid infant stimuli and point to a particularly prompt maternal response to infant distress cues.

Fat mass and obesity associated gene (FTO expression is regulated negatively by the transcription factor Foxa2.

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Jianjin Guo

Full Text Available Fat mass and obesity associated gene (FTO is the first gene associated with body mass index (BMI and risk for diabetes. FTO is highly expressed in the brain and pancreas, and is involved in regulating dietary intake and energy expenditure. To investigate the transcriptional regulation of FTO expression, we created 5'-deletion constructs of the FTO promoter to determine which transcription factors are most relevant to FTO expression. The presence of an activation region at -201/+34 was confirmed by luciferase activity analysis. A potential Foxa2 (called HNF-3β binding site and an upstream stimulatory factor (USF-binding site was identified in the -100 bp fragment upstream of the transcription start site (TSS. Furthermore, using mutagenesis, we identified the Foxa2 binding sequence (-26/-14 as a negative regulatory element to the activity of the human FTO promoter. The USF binding site did not affect the FTO promoter activity. Chromatin immunoprecipitation (ChIP assays were performed to confirm Foxa2 binding to the FTO promoter. Overexpression of Foxa2 in HEK 293 cells significantly down-regulated FTO promoter activity and expression. Conversely, knockdown of Foxa2 by siRNA significantly up-regulated FTO expression. These findings suggest that Foxa2 negatively regulates the basal transcription and expression of the human FTO gene.

Immunohistochemical expression profiles of mucin antigens in salivary gland mucoepidermoid carcinoma: MUC4- and MUC6-negative expression predicts a shortened survival in the early postoperative phase.

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Honjo, Kie; Hiraki, Tsubasa; Higashi, Michiyo; Noguchi, Hirotsugu; Nomoto, Mitsuharu; Yoshimura, Takuya; Batra, Surinder K; Yonezawa, Suguru; Semba, Ichiro; Nakamura, Norifumi; Tanimoto, Akihide; Yamada, Sohsuke

2018-02-01

In mucoepidermoid carcinoma (MEC), the most common salivary gland carcinoma, there is a lack of novel prognostic markers, but post-operative early recurrence strongly affects the clinical course and a poor outcome. It is critical to predict which MEC patients are prone to develop recurrence/metastases. Mucins play pivotal roles in influencing cancer biology, thus affecting cell differentiation, adhesion, carcinoma invasion, aggressiveness and/or metastatic potential. Our aim is to elucidate the significance of expression profiles for mucins, particularly MUC4 and MUC6, and their correlations with various clinicopathological features and recurrence in salivary gland MECs. We performed immunohistochemical analyses on patients with surgically resected primary MEC using antibodies against mucin core proteins MUC4/8G7 and MUC6/CLH5 in 73 paraffin-embedded samples. Recurrence was noted in 15 of 73 (20.5%) patients. MUC4 or MUC6 expression was considered to be negative when <30% or 0% of the MEC cells showed positive staining, respectively. MUC4- and/or MUC6-negative expression respectively and variably showed a significant relationship to pathological tumor high-grade, the presence of lymphovascular invasion, lymph node metastasis and/or tumor-related death. In addition, MUC4 showed significantly negative co-expression with MUC6. Kaplan-Meier analyses revealed that not only single MUC4/6-negative expression but also the combination of both predicted significantly shorter disease-free and disease-specific survivals in MECs, especially within the first two years postoperatively. Therefore, each mucin plays a pivotal role in the pathogenesis of MEC progression. The detection of MUC4 and/or MUC6 might be a powerful parameter in the clinical management of MECs in the early postsurgical phase.

Facial expression judgments support a socio-relational model, rather than a negativity bias model of political psychology.

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Vigil, Jacob M; Strenth, Chance

2014-06-01

Self-reported opinions and judgments may be more rooted in expressive biases than in cognitive processing biases, and ultimately operate within a broader behavioral style for advertising the capacity - versus the trustworthiness - dimension of human reciprocity potential. Our analyses of facial expression judgments of likely voters are consistent with this thesis, and directly contradict one major prediction from the authors' "negativity-bias" model.

Validation of expression patterns for nine miRNAs in 204 lymph-node negative breast cancers.

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Kristin Jonsdottir

Full Text Available INTRODUCTION: Although lymph node negative (LN- breast cancer patients have a good 10-years survival (∼85%, most of them still receive adjuvant therapy, while only some benefit from this. More accurate prognostication of LN- breast cancer patient may reduce over- and under-treatment. Until now proliferation is the strongest prognostic factor for LN- breast cancer patients. The small molecule microRNA (miRNA has opened a new window for prognostic markers, therapeutic targets and/or therapeutic components. Previously it has been shown that miR-18a/b, miR-25, miR-29c and miR-106b correlate to high proliferation. METHODS: The current study validates nine miRNAs (miR-18a/b miR-25, miR-29c, miR-106b, miR375, miR-424, miR-505 and let-7b significantly correlated with established prognostic breast cancer biomarkers. Total RNA was isolated from 204 formaldehyde-fixed paraffin embedded (FFPE LN- breast cancers and analyzed with quantitative real-time Polymerase Chain Reaction (qPCR. Independent T-test was used to detect significant correlation between miRNA expression level and the different clinicopathological features for breast cancer. RESULTS: Strong and significant associations were observed for high expression of miR-18a/b, miR-106b, miR-25 and miR-505 to high proliferation, oestrogen receptor negativity and cytokeratin 5/6 positivity. High expression of let-7b, miR-29c and miR-375 was detected in more differentiated tumours. Kaplan-Meier survival analysis showed that patients with high miR-106b expression had an 81% survival rate vs. 95% (P = 0.004 for patients with low expression. CONCLUSION: High expression of miR-18a/b are strongly associated with basal-like breast cancer features, while miR-106b can identify a group with higher risk for developing distant metastases in the subgroup of Her2 negatives. Furthermore miR-106b can identify a group of patients with 100% survival within the otherwise considered high risk group of patients with

Nuclear Kaiso expression is associated with high grade and triple-negative invasive breast cancer.

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Jeroen F Vermeulen

Full Text Available Kaiso is a BTB/POZ transcription factor that is ubiquitously expressed in multiple cell types and functions as a transcriptional repressor and activator. Little is known about Kaiso expression and localization in breast cancer. Here, we have related pathological features and molecular subtypes to Kaiso expression in 477 cases of human invasive breast cancer. Nuclear Kaiso was predominantly found in invasive ductal carcinoma (IDC (p = 0.007, while cytoplasmic Kaiso expression was linked to invasive lobular carcinoma (ILC (p = 0.006. Although cytoplasmic Kaiso did not correlate to clinicopathological features, we found a significant correlation between nuclear Kaiso, high histological grade (p = 0.023, ERα negativity (p = 0.001, and the HER2-driven and basal/triple-negative breast cancers (p = 0.018. Interestingly, nuclear Kaiso was also abundant in BRCA1-associated breast cancer (p<0.001 and invasive breast cancer overexpressing EGFR (p = 0.019. We observed a correlation between nuclear Kaiso and membrane-localized E-cadherin and p120-catenin (p120 (p<0.01. In contrast, cytoplasmic p120 strongly correlated with loss of E-cadherin and low nuclear Kaiso (p = 0.005. We could confirm these findings in human ILC cells and cell lines derived from conditional mouse models of ILC. Moreover, we present functional data that substantiate a mechanism whereby E-cadherin controls p120-mediated relief of Kaiso-dependent gene repression. In conclusion, our data indicate that nuclear Kaiso is common in clinically aggressive ductal breast cancer, while cytoplasmic Kaiso and a p120-mediated relief of Kaiso-dependent transcriptional repression characterize ILC.

Negative Leadership

Science.gov (United States)

2013-03-01

Negative Leadership by Colonel David M. Oberlander United States Army United States Army War...SUBTITLE Negative Leadership 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Colonel David M...Dr. Richard C. Bullis Department of Command Leadership , and Management 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING

Why expressive suppression does not pay? Cognitive costs of negative emotion suppression: The mediating role of subjective tense-arousal

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Szczygieł Dorota

2015-09-01

Full Text Available The aim of this paper was to contribute to a broader understanding of the cognitive consequences of expressive suppression. Specifically, we examined whether the deteriorating effect of expressive suppression on cognitive functioning is caused by tense arousal enhanced by suppression. Two experiments were performed in order to test this prediction. In both studies we tested the effect of expressive suppression on working memory, as measured with a backwards digit-span task (Study 1, N = 43 and anagram problem-solving task (Study 2, N = 60. In addition, in Study 2 we tested whether expressive suppression degrades memory of the events that emerged during the period of expressive suppression. Both studies were conducted in a similar design: Participants watched a film clip which evoked negative emotions (i.e. disgust in Study 1 and a combination of sadness and anxiety in Study 2 under the instruction to suppress those negative emotions or (in the control condition to simply watch the film. The results of these experiments lead to three conclusions. First, the results reveal that expressive suppression degrades memory of the events that emerged during the period of expressive suppression and leads to poorer performance on working memory tasks, as measured with a backwards digit-span task and anagram problem-solving task. Second, the results indicate that expressive suppression leads to a significant increase in subjective tense arousal. Third, the results support our prediction that expressive suppression decreases cognitive performance through its effects on subjective tense arousal. The results of the Study 1 show that tense arousal activated during expressive suppression of disgust fully mediates the negative effect of suppression on working memory as measured with a backwards digit-span task. The results of Study 2 reveal that subjective tense arousal elicited while suppressing sadness and anxiety mediates both the effect of suppression on

Gene expression in triple-negative breast cancer in relation to survival.

Science.gov (United States)

Wang, Shuyang; Beeghly-Fadiel, Alicia; Cai, Qiuyin; Cai, Hui; Guo, Xingyi; Shi, Liang; Wu, Jie; Ye, Fei; Qiu, Qingchao; Zheng, Ying; Zheng, Wei; Bao, Ping-Ping; Shu, Xiao-Ou

2018-05-10

The identification of biomarkers related to the prognosis of triple-negative breast cancer (TNBC) is critically important for improved understanding of the biology that drives TNBC progression. We evaluated gene expression in total RNA isolated from formalin-fixed paraffin-embedded tumor samples using the NanoString nCounter assay for 469 TNBC cases from the Shanghai Breast Cancer Survival Study. We used Cox regression to quantify Hazard Ratios (HR) and corresponding confidence intervals (CI) for overall survival (OS) and disease-free survival (DFS) in models that included adjustment for breast cancer intrinsic subtype. Of 302 genes in our discovery analysis, 22 were further evaluated in relation to OS among 134 TNBC cases from the Nashville Breast Health Study and the Southern Community Cohort Study; 16 genes were further evaluated in relation to DFS in 335 TNBC cases from four gene expression omnibus datasets. Fixed-effect meta-analysis was used to combine results across data sources. Twofold higher expression of EOMES (HR 0.90, 95% CI 0.83-0.97), RASGRP1 (HR 0.89, 95% CI 0.82-0.97), and SOD2 (HR 0.80, 95% CI 0.66-0.96) was associated with better OS. Twofold higher expression of EOMES (HR 0.89, 95% CI 0.81-0.97) and RASGRP1 (HR 0.87, 95% CI 0.81-0.95) was also associated with better DFS. On the contrary, a doubling of FA2H (HR 1.14, 95% CI 1.06-1.22) and GSPT1 (HR 1.33, 95% CI 1.14-1.55) expression was associated with shorter DFS. We identified five genes (EOMES, FA2H, GSPT1, RASGRP1, and SOD2) that may serve as potential prognostic biomarkers and/or therapeutic targets for TNBC.

A CLDN1-negative phenotype predicts poor prognosis in triple-negative breast cancer.

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Fei Ma

Full Text Available INTRODUCTION: Triple-negative breast cancer (TNBC is a heterogeneous disease with no definitive prognostic markers. As a major component of tight junctions, claudins (CLDNs presumably play an important role in carcinogenesis and progression of breast cancer. This study was aimed at determining the relationship between the expression of CLDNs and the clinical outcomes of TNBCs. MATERIALS AND METHODS: The surgical specimens of primary breast tumors from a consecutive cohort of 173 TNBC patients were retrospectively collected. The membranous expression of CLDN1, CLDN2, CLDN4, and CLDN7 was measured by immunohistochemistry. Then, the associations between CLDN expression, clinicopathological features, and clinical outcomes were assessed. RESULTS: Positive CLDN1, CLDN2, CLDN4, and CLDN7 membrane expression was detected in 44.5%, 54.9%, 76.9%, and 73.4% of the cohort specimens, respectively. A lack of CLDN1 expression was related to only lymph node metastasis (P = 0.014. The rate of CLDN4-positive tumors was significantly increased in tumors of a higher grade (P = 0.003. Importantly, negative CLDN1 expression was associated with worse relapse-free survival (RFS in both lymph node positive (LN+ and negative (LN- cases (both P<0.001. Similarly it was also associated with shorter overall survival (OS(P = 0.003 in LN+ cases; P = 0.018 in LN- cases. In the LN+ subgroup, CLDN2-negative cases had a significantly higher risk of recurrence (P = 0.008. Multivariate analysis revealed that negative CLDN1 expression was an independent prognostic factor for high risk of both recurrence and death (HR 5.529, 95% CI 2.664-11.475, P<0.001; HR 3.459, 95% CI 1.555-7.696, P = 0.002. However, neither CLDN4 nor CLDN7 expression was associated with survival. CONCLUSION: In TNBC, the CLDN1-negative phenotype predicts a high risk of recurrence and death. The absence of CLDN1 expression is strongly suggested to be an independent adverse prognostic factor

Negative Facial Expressions – But Not Visual Scenes – Enhance Human Working Memory in Younger and Older Participants

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Flávia Schechtman Belham

2017-09-01

Full Text Available Many studies have investigated the influence of emotion on memory processes across the human lifespan. Some results have shown older adults (OA performing better with positive stimuli, some with negative items, whereas some found no impact of emotional valence. Here we tested, in two independent studies, how younger adults (YA and OA would perform in a visuospatial working memory (VSWM task with positive, negative, and neutral images. The task consisted of identifying the new location of a stimulus in a crescent set of identical stimuli presented in different locations in a touch-screen monitor. In other words, participants should memorize the locations previously occupied to identify the new location. For each trial, the number of occupied locations increased until 8 or until a mistake was made. In study 1, 56 YA and 38 OA completed the task using images from the International Affective Picture System (IAPS. Results showed that, although YA outperformed OA, no effects of emotion were found. In study 2, 26 YA and 25 OA were tested using facial expressions as stimuli. Data from this study showed that negative faces facilitated performance and this effect did not differ between age groups. No differences were found between men and women. Taken together, our findings suggest that YA and OA’s VSWM can be influenced by the emotional valence of the information, though this effect was present only for facial stimuli. Presumably, this may have happened due to the social and biological importance of such stimuli, which are more effective in transmitting emotions than IAPS images. Critically, our results also indicate that the mixed findings in the literature about the influence of aging on the interactions between memory and emotion may be caused by the use of different stimuli and methods. This possibility should be kept in mind in future studies about memory and emotion across the lifespan.

Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

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Pistelli, Mirco, E-mail: mirco.pistelli@alice.it; Caramanti, Miriam [Clinica di Oncologia Medica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona 60020 (Italy); Biscotti, Tommasina; Santinelli, Alfredo [Anatomia Patologica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona 60020 (Italy); Pagliacci, Alessandra; De Lisa, Mariagrazia; Ballatore, Zelmira; Ridolfi, Francesca; Maccaroni, Elena; Bracci, Raffaella; Berardi, Rossana; Battelli, Nicola; Cascinu, Stefano [Clinica di Oncologia Medica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona 60020 (Italy)

2014-06-27

Background: Triple-negative breast cancers (TNBC) are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR) is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001) and a lympho-vascular invasion (p = 0.01), but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72) or overall survival (p = 0.93). Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target.

Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

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Mirco Pistelli

2014-06-01

Full Text Available Background: Triple-negative breast cancers (TNBC are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001 and a lympho-vascular invasion (p = 0.01, but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72 or overall survival (p = 0.93. Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target.

Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

International Nuclear Information System (INIS)

Pistelli, Mirco; Caramanti, Miriam; Biscotti, Tommasina; Santinelli, Alfredo; Pagliacci, Alessandra; De Lisa, Mariagrazia; Ballatore, Zelmira; Ridolfi, Francesca; Maccaroni, Elena; Bracci, Raffaella; Berardi, Rossana; Battelli, Nicola; Cascinu, Stefano

2014-01-01

Background: Triple-negative breast cancers (TNBC) are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR) is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001) and a lympho-vascular invasion (p = 0.01), but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72) or overall survival (p = 0.93). Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target

Negative Effects of Psychological Treatments: An Exploratory Factor Analysis of the Negative Effects Questionnaire for Monitoring and Reporting Adverse and Unwanted Events.

Science.gov (United States)

Rozental, Alexander; Kottorp, Anders; Boettcher, Johanna; Andersson, Gerhard; Carlbring, Per

2016-01-01

Research conducted during the last decades has provided increasing evidence for the use of psychological treatments for a number of psychiatric disorders and somatic complaints. However, by focusing only on the positive outcomes, less attention has been given to the potential of negative effects. Despite indications of deterioration and other adverse and unwanted events during treatment, little is known about their occurrence and characteristics. Hence, in order to facilitate research of negative effects, a new instrument for monitoring and reporting their incidence and impact was developed using a consensus among researchers, self-reports by patients, and a literature review: the Negative Effects Questionnaire. Participants were recruited via a smartphone-delivered self-help treatment for social anxiety disorder and through the media (N = 653). An exploratory factor analysis was performed, resulting in a six-factor solution with 32 items, accounting for 57.64% of the variance. The derived factors were: symptoms, quality, dependency, stigma, hopelessness, and failure. Items related to unpleasant memories, stress, and anxiety were experienced by more than one-third of the participants. Further, increased or novel symptoms, as well as lack of quality in the treatment and therapeutic relationship rendered the highest self-reported negative impact. In addition, the findings were discussed in relation to prior research and other similar instruments of adverse and unwanted events, giving credence to the items that are included. The instrument is presently available in eleven different languages and can be freely downloaded and used from www.neqscale.com.

amiA is a negative regulator of acetamidase expression in Mycobacterium smegmatis

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Turner Jane

2001-08-01

Full Text Available Abstract Background The acetamidase of Mycobacterium smegmatis is a highly inducible enzyme. Expression of this enzyme is increased 100-fold when the substrate acetamide is present. The acetamidase gene is found immediately downstream of three open reading frames. Two of these are proposed to be involved in regulation. Results We constructed a deletion mutant in one of the upstream ORFs (amiA. This mutant (Mad1 showed a constitutively high level of acetamidase expression. We identified four promoters in the upstream region using a β-galactosidase reporter gene. One of these (P2 was inducible in the wild-type, but was constitutively active in Mad1. Conclusions These results demonstrate that amiA encodes a negative regulatory protein which interacts with P2. Since amiA has homology to DNA-binding proteins, it is likely that it exerts the regulatory effect by binding to the promoter to prevent transcription.

Ribavirin restores ESR1 gene expression and tamoxifen sensitivity in ESR1 negative breast cancer cell lines

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Sappok Anne

2011-12-01

Full Text Available Abstract Tumor growth is estrogen independent in approximately one-third of all breast cancers, which makes these patients unresponsive to hormonal treatment. This unresponsiveness to hormonal treatment may be explained through the absence of the estrogen receptor alpha (ESR1. The ESR1 gene re-expression through epigenetic modulators such as DNA methyltransferase inhibitors and/or histone deacetylase inhibitors restores tamoxifen sensitivity in ESR1 negative breast cancer cell lines and opens new treatment horizons in patients who were previously associated with a poor prognosis. In the study presented herein, we tested the ability of ribavirin, which shares some structural similarities with the DNA-methyltransferase inhibitor 5-azacytidine and which is widely known as an anti-viral agent in the treatment of hepatitis C, to restore ESR1 gene re-expression in ESR1 negative breast cancer cell lines. In our study we identified ribavirin to restore ESR1 gene re-expression alone and even more in combination with suberoylanilide hydroxamic acid (SAHA - up to 276 fold induction. Ribavirin and analogs could pave the way to novel translational research projects that aim to restore ESR1 gene re-expression and thus the susceptibility to tamoxifen-based endocrine treatment strategies.

Triggering receptor expressed on myeloid cells-2 fine-tunes inflammatory responses in murine Gram-negative sepsis

DEFF Research Database (Denmark)

Schmidt Thøgersen, Mariane; Gawish, Riem; Martins, Rui

2015-01-01

During infections, TLR-mediated responses require tight regulation to allow for pathogen removal, while preventing overwhelming inflammation and immunopathology. The triggering receptor expressed on myeloid cells (TREM)-2 negatively regulates inflammation by macrophages and impacts on phagocytosis...... was followed by an accelerated resolution and ultimately improved survival, associated with the induction of the negative regulator A20. Upon infection with Escherichia coli, the otherwise beneficial effect of an exaggerated early immune response in TREM-2(-/-) animals was counteracted by a 50% reduction...... in bacterial phagocytosis. In line with this, TREM-2(-/-) peritoneal macrophages (PMs) exhibited augmented inflammation following TLR4 stimulation, demonstrating the presence and negative regulatory functionality of TREM-2 on primary PMs. Significantly, we identified a high turnover rate because TREM-2 RNA...

Human apolipoprotein CIII gene expression is regulated by positive and negative cis-acting elements and tissue-specific protein factors

International Nuclear Information System (INIS)

Reue, K.; Leff, T.; Breslow, J.L.

1988-01-01

Apolipoprotein CIII (apoCIII) is a major protein constituent of triglyceride-rich lipoproteins and is synthesized primarily in the liver. Cis-acting DNA elements required for liver-specific apoCIII gene transcription were identified with transient expression assays in the human hepatoma (HepG2) and epithelial carcinoma (HeLa) cell lines. In liver cells, 821 nucleotides of the human apoCIII gene 5'-flanking sequence were required for maximum levels of gene expression, while the proximal 110 nucleotides alone were sufficient. No expression was observed in similar studies with HeLa cells. The level of expression was modulated by a combination of positive and negative cis-acting sequences, which interact with distinct sets of proteins from liver and HeLa cell nuclear extracts. The proximal positive regulatory region shares homology with similarly located sequences of other genes strongly expressed in the liver, including α 1 -antitrypsin and other apolipoprotein genes. The negative regulatory region is striking homologous to the human β-interferon gene regulatory element. The distal positive region shares homology with some viral enhancers and has properties of a tissue-specific enhancer. The regulation of the apoCIII gene is complex but shares features with other genes, suggesting shuffling of regulatory elements as a common mechanism for cell type-specific gene expression

Partial least squares based gene expression analysis in estrogen receptor positive and negative breast tumors.

Science.gov (United States)

Ma, W; Zhang, T-F; Lu, P; Lu, S H

2014-01-01

Breast cancer is categorized into two broad groups: estrogen receptor positive (ER+) and ER negative (ER-) groups. Previous study proposed that under trastuzumab-based neoadjuvant chemotherapy, tumor initiating cell (TIC) featured ER- tumors response better than ER+ tumors. Exploration of the molecular difference of these two groups may help developing new therapeutic strategies, especially for ER- patients. With gene expression profile from the Gene Expression Omnibus (GEO) database, we performed partial least squares (PLS) based analysis, which is more sensitive than common variance/regression analysis. We acquired 512 differentially expressed genes. Four pathways were found to be enriched with differentially expressed genes, involving immune system, metabolism and genetic information processing process. Network analysis identified five hub genes with degrees higher than 10, including APP, ESR1, SMAD3, HDAC2, and PRKAA1. Our findings provide new understanding for the molecular difference between TIC featured ER- and ER+ breast tumors with the hope offer supports for therapeutic studies.

Remote sensing of gene expression in Planta: transgenic plants as monitors of exogenous stress perception in extraterrestrial environments

Science.gov (United States)

Manak, Michael S.; Paul, Anna-Lisa; Sehnke, Paul C.; Ferl, Robert J.

2002-01-01

Transgenic arabidopsis plants containing the alcohol dehydrogenase (Adh) gene promoter fused to the green fluorescent protein (GFP) reporter gene were developed as biological sensors for monitoring physiological responses to unique environments. Plants were monitored in vivo during exposure to hypoxia, high salt, cold, and abcissic acid in experiments designed to characterize the utility and responses of the Adh/GFP biosensors. Plants in the presence of environmental stimuli that induced the Adh promoter responded by expressing GFP, which in turn generated a detectable fluorescent signal. The GFP signal degraded when the inducing stimulus was removed. Digital imaging of the Adh/GFP plants exposed to each of the exogenous stresses demonstrated that the stress-induced gene expression could be followed in real time. The experimental results established the feasibility of using a digital monitoring system for collecting gene expression data in real time from Transgenic Arabidopsis Gene Expression System (TAGES) biosensor plants during space exploration experiments.

THE PROGNOSIS SIGNIFICANCE OF CATHEPSIN-D EXPRESSION IN THE DIFFERENT LOCATIONS IN AXILLARY NODES NEGATIVE CARCINOMA

Institute of Scientific and Technical Information of China (English)

无

2001-01-01

Objective: The aim of this study was to investigate Cathepsin-D (Cath-D) expression in different location and its relationship with prognosis in the axillary lymph nodes negative (ANN) breast cancer patients. Methods: Cath-D expression in 192 cases of breast carcinoma were examined by immunohistochemistry. Depending on different parts of expression, three evaluating methods were used, compared and analysed. Results: The positive rate of Cath-D expression in ANN breast cancer with poor prognosis group and axillary nodes positive (ANP) group were significantly higher than that in ANN breast cancer with good prognosis group (x2=23.20, P0.05). Cath-D expression in stromal cells had no statistical difference among the three groups (x2=1.56, P>0.05). When the Cath-D expression in cancer and stromal cells were counted into the positive rate, it was near the same (u1=0.47, u2=1.41, P>0.05). Conclusion: These results suggest that Cath-D expression is one of the powerful prognostic markers in ANN breast cancer. It's a reliable, practical, and convenient method to observe and evaluate Cath-D expression in cancer cells.

Expression profiling of nuclear receptors in breast cancer identifies TLX as a mediator of growth and invasion in triple-negative breast cancer.

Science.gov (United States)

Lin, Meng-Lay; Patel, Hetal; Remenyi, Judit; Banerji, Christopher R S; Lai, Chun-Fui; Periyasamy, Manikandan; Lombardo, Ylenia; Busonero, Claudia; Ottaviani, Silvia; Passey, Alun; Quinlan, Philip R; Purdie, Colin A; Jordan, Lee B; Thompson, Alastair M; Finn, Richard S; Rueda, Oscar M; Caldas, Carlos; Gil, Jesus; Coombes, R Charles; Fuller-Pace, Frances V; Teschendorff, Andrew E; Buluwela, Laki; Ali, Simak

2015-08-28

The Nuclear Receptor (NR) superfamily of transcription factors comprises 48 members, several of which have been implicated in breast cancer. Most important is estrogen receptor-α (ERα), which is a key therapeutic target. ERα action is facilitated by co-operativity with other NR and there is evidence that ERα function may be recapitulated by other NRs in ERα-negative breast cancer. In order to examine the inter-relationships between nuclear receptors, and to obtain evidence for previously unsuspected roles for any NRs, we undertook quantitative RT-PCR and bioinformatics analysis to examine their expression in breast cancer. While most NRs were expressed, bioinformatic analyses differentiated tumours into distinct prognostic groups that were validated by analyzing public microarray data sets. Although ERα and progesterone receptor were dominant in distinguishing prognostic groups, other NR strengthened these groups. Clustering analysis identified several family members with potential importance in breast cancer. Specifically, RORγ is identified as being co-expressed with ERα, whilst several NRs are preferentially expressed in ERα-negative disease, with TLX expression being prognostic in this subtype. Functional studies demonstrated the importance of TLX in regulating growth and invasion in ERα-negative breast cancer cells.

Bioactive dietary supplements reactivate ER expression in ER-negative breast cancer cells by active chromatin modifications.

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Syed M Meeran

Full Text Available Breast cancer is the most common cancer and the leading cause of cancer death in women. Although tamoxifen therapy is successful for some patients, it does not provide adequate benefit for those who have estrogen receptor (ER-negative cancers. Therefore, we approached novel treatment strategies by combining two potential bioactive dietary supplements for the reactivation of ERα expression for effective treatment of ERα-negative breast cancer with tamoxifen. Bioactive dietary supplements such as green tea polyphenols (GTPs and sulforaphane (SFN inhibit DNA methyltransferases (DNMTs and histone deacetylases (HDACs, respectively, which are of central importance to cancer prevention. In the present study, we have observed that treatment of ERα-negative breast cancer cells with GTPs and SFN alone or in combination leads to the reactivation of ERα expression. The combination of 20 µg/mL GTPs and 5 µM SFN was found to be the optimal dose of ERα-reactivation at 3 days in MDA-MB-231 cells. The reactivation of ERα expression was consistently correlated with ERα promoter hypomethylation and hyperacetylation. Chromatin immunoprecipitation (ChIP analysis of the ERα promoter revealed that GTPs and SFN altered the binding of ERα-transcriptional co-repressor complex thereby contributing to ERα-reactivation. In addition, treatment with tamoxifen in combination with GTPs and SFN significantly increased both cell death and inhibition of cellular proliferation in MDA-MB-231 cells in comparison to treatment with tamoxifen alone. Collectively, our findings suggest that a novel combination of bioactive-HDAC inhibitors with bioactive-demethylating agents is a promising strategy for the effective treatment of hormonal refractory breast cancer with available anti-estrogens.

Role of negative affects in pathophysiology and clinical expression of irritable bowel syndrome.

Science.gov (United States)

Muscatello, Maria Rosaria A; Bruno, Antonio; Scimeca, Giuseppe; Pandolfo, Gianluca; Zoccali, Rocco A

2014-06-28

Irritable bowel syndrome (IBS) is regarded as a multifactorial disease in which alterations in the brain-gut axis signaling play a major role. The biopsychosocial model applied to the understanding of IBS pathophysiology assumes that psychosocial factors, interacting with peripheral/central neuroendocrine and immune changes, may induce symptoms of IBS, modulate symptom severity, influence illness experience and quality of life, and affect outcome. The present review focuses on the role of negative affects, including depression, anxiety, and anger, on pathogenesis and clinical expression of IBS. The potential role of the autonomic nervous system, stress-hormone system, and immune system in the pathophysiology of both negative affects and IBS are taken into account. Psychiatric comorbidity and subclinical variations in levels of depression, anxiety, and anger are further discussed in relation to the main pathophysiological and symptomatic correlates of IBS, such as sensorimotor functions, gut microbiota, inflammation/immunity, and symptom reporting.

Negative Effects of Psychological Treatments: An Exploratory Factor Analysis of the Negative Effects Questionnaire for Monitoring and Reporting Adverse and Unwanted Events

Science.gov (United States)

Kottorp, Anders; Boettcher, Johanna; Andersson, Gerhard; Carlbring, Per

2016-01-01

Research conducted during the last decades has provided increasing evidence for the use of psychological treatments for a number of psychiatric disorders and somatic complaints. However, by focusing only on the positive outcomes, less attention has been given to the potential of negative effects. Despite indications of deterioration and other adverse and unwanted events during treatment, little is known about their occurrence and characteristics. Hence, in order to facilitate research of negative effects, a new instrument for monitoring and reporting their incidence and impact was developed using a consensus among researchers, self-reports by patients, and a literature review: the Negative Effects Questionnaire. Participants were recruited via a smartphone-delivered self-help treatment for social anxiety disorder and through the media (N = 653). An exploratory factor analysis was performed, resulting in a six-factor solution with 32 items, accounting for 57.64% of the variance. The derived factors were: symptoms, quality, dependency, stigma, hopelessness, and failure. Items related to unpleasant memories, stress, and anxiety were experienced by more than one-third of the participants. Further, increased or novel symptoms, as well as lack of quality in the treatment and therapeutic relationship rendered the highest self-reported negative impact. In addition, the findings were discussed in relation to prior research and other similar instruments of adverse and unwanted events, giving credence to the items that are included. The instrument is presently available in eleven different languages and can be freely downloaded and used from www.neqscale.com. PMID:27331907

Negative Effects of Psychological Treatments: An Exploratory Factor Analysis of the Negative Effects Questionnaire for Monitoring and Reporting Adverse and Unwanted Events.

Directory of Open Access Journals (Sweden)

Alexander Rozental

Full Text Available Research conducted during the last decades has provided increasing evidence for the use of psychological treatments for a number of psychiatric disorders and somatic complaints. However, by focusing only on the positive outcomes, less attention has been given to the potential of negative effects. Despite indications of deterioration and other adverse and unwanted events during treatment, little is known about their occurrence and characteristics. Hence, in order to facilitate research of negative effects, a new instrument for monitoring and reporting their incidence and impact was developed using a consensus among researchers, self-reports by patients, and a literature review: the Negative Effects Questionnaire. Participants were recruited via a smartphone-delivered self-help treatment for social anxiety disorder and through the media (N = 653. An exploratory factor analysis was performed, resulting in a six-factor solution with 32 items, accounting for 57.64% of the variance. The derived factors were: symptoms, quality, dependency, stigma, hopelessness, and failure. Items related to unpleasant memories, stress, and anxiety were experienced by more than one-third of the participants. Further, increased or novel symptoms, as well as lack of quality in the treatment and therapeutic relationship rendered the highest self-reported negative impact. In addition, the findings were discussed in relation to prior research and other similar instruments of adverse and unwanted events, giving credence to the items that are included. The instrument is presently available in eleven different languages and can be freely downloaded and used from www.neqscale.com.

[Expression of negative emotional responses to the 2011 Great East Japan Earthquake: Analysis of big data from social media].

Science.gov (United States)

Miura, Asako; Komori, Masashi; Matsumura, Naohiro; Maeda, Kazutoshi

2015-06-01

In this article, we investigated the expression of emotional responses to the 2011 Great East Japan Earthquake by analyzing the frequency of negative emotional terms in tweets posted on Twitter, one of the most popular social media platforms. We focused on differences in time-series variations and diurnal changes between two kinds of disasters: natural disasters (earthquakes and tsunamis) and nuclear accidents. The number of tweets containing negative emotional responses increased sharply shortly after the first huge earthquake and decreased over time, whereas tweets about nuclear accidents showed no correlation with elapsed time. Expressions of anxiety about natural disasters had a circadian rhythm, with a peak at midnight, whereas expressions of anger about the nuclear accident were highly sensitive to critical events related to the accident. These findings were discussed in terms of similarities and differences compared to earlier studies on emotional responses in social media.

Orphan nuclear receptor Nur77 is a novel negative regulator of endothelin-1 expression in vascular endothelial cells.

Science.gov (United States)

Qin, Qing; Chen, Ming; Yi, Bing; You, Xiaohua; Yang, Ping; Sun, Jianxin

2014-12-01

Endothelin-1 (ET-1) produced by vascular endothelial cells plays essential roles in the regulation of vascular tone and development of cardiovascular diseases. The objective of this study is to identify novel regulators implicated in the regulation of ET-1 expression in vascular endothelial cells (ECs). By using quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), we show that either ectopic expression of orphan nuclear receptor Nur77 or pharmacological activation of Nur77 by 6-mercaptopurine (6-MP) substantially inhibits ET-1 expression in human umbilical vein endothelial cells (HUVECs), under both basal and thrombin-stimulated conditions. Furthermore, thrombin-stimulated ET expression is significantly augmented in both Nur77 knockdown ECs and aort from Nur77 knockout mice, suggesting that Nur77 is a negative regulator of ET-1 expression. Inhibition of ET-1 expression by Nur77 occurs at gene transcriptional levels, since Nur77 potently inhibits ET-1 promoter activity, without affecting ET-1 mRNA stability. As shown in electrophoretic mobility shift assay (EMSA), Nur77 overexpression markedly inhibits both basal and thrombin-stimulated transcriptional activity of AP-1. Mechanistically, we demonstrate that Nur77 specially interacts with c-Jun and inhibits AP-1 dependent c-Jun promoter activity, which leads to a decreased expression of c-Jun, a critical component involved in both AP-1 transcriptional activity and ET-1 expression in ECs. These findings demonstrate that Nur77 is a novel negative regulator of ET-1 expression in vascular ECs through an inhibitory interaction with the c-Jun/AP-1 pathway. Activation of Nur77 may represent a useful therapeutic strategy for preventing certain cardiovascular diseases, such as atherosclerosis and pulmonary artery hypertension. Copyright © 2014 Elsevier Ltd. All rights reserved.

Positive and negative expressions of shyness in toddlers: are they related to anxiety in the same way?

NARCIS (Netherlands)

Colonnesi, C.; Napoleone, E.; Bögels, S.M.

2014-01-01

Shyness has generally been investigated as a negative and unpleasant emotional state, strongly related to social anxiety and loneliness. However, recent evidence suggests that shyness may have a positive and socially adaptive form. We examined whether the positive expression of shyness differs from

An error-related negativity potential investigation of response monitoring function in individuals with Internet addiction disorder

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Zhenhe eZhou

2013-09-01

Full Text Available Internet addiction disorder (IAD is an impulse disorder or at least related to impulse control disorder. Deficits in executive functioning, including response monitoring, have been proposed as a hallmark feature of impulse control disorders. The error-related negativity (ERN reflects individual’s ability to monitor behavior. Since IAD belongs to a compulsive-impulsive spectrum disorder, theoretically, it should present response monitoring functional deficit characteristics of some disorders, such as substance dependence, ADHD or alcohol abuse, testing with an Erikson flanker task. Up to now, no studies on response monitoring functional deficit in IAD were reported. The purpose of the present study was to examine whether IAD displays response monitoring functional deficit characteristics in a modified Erikson flanker task.23 subjects were recruited as IAD group. 23 matched age, gender and education healthy persons were recruited as control group. All participants completed the modified Erikson flanker task while measured with event-related potentials (ERPs. IAD group made more total error rates than did controls (P < 0.01; Reactive times for total error responses in IAD group were shorter than did controls (P < 0.01. The mean ERN amplitudes of total error response conditions at frontal electrode sites and at central electrode sites of IAD group were reduced compared with control group (all P < 0.01. These results revealed that IAD displays response monitoring functional deficit characteristics and shares ERN characteristics of compulsive-impulsive spectrum disorder.

Response and binding elements for ligand-dependent positive transcription factors integrate positive and negative regulation of gene expression

International Nuclear Information System (INIS)

Rosenfeld, M.G.; Glass, C.K.; Adler, S.; Crenshaw, E.B. III; He, X.; Lira, S.A.; Elsholtz, H.P.; Mangalam, H.J.; Holloway, J.M.; Nelson, C.; Albert, V.R.; Ingraham, H.A.

1988-01-01

Accurate, regulated initiation of mRNA transcription by RNA polymerase II is dependent on the actions of a variety of positive and negative trans-acting factors that bind cis-acting promoter and enhancer elements. These transcription factors may exert their actions in a tissue-specific manner or function under control of plasma membrane or intracellular ligand-dependent receptors. A major goal in the authors' laboratory has been to identify the molecular mechanisms responsible for the serial activation of hormone-encoding genes in the pituitary during development and the positive and negative regulation of their transcription. The anterior pituitary gland contains phenotypically distinct cell types, each of which expresses unique trophic hormones: adrenocorticotropic hormone, thyroid-stimulating hormone, prolactin, growth hormone, and follicle-stimulating hormone/luteinizing hormone. The structurally related prolactin and growth hormone genes are expressed in lactotrophs and somatotrophs, respectively, with their expression virtually limited to the pituitary gland. The reported transient coexpression of these two structurally related neuroendocrine genes raises the possibility that the prolactin and growth hormone genes are developmentally controlled by a common factor(s)

Gibberellin Application at Pre-Bloom in Grapevines Down-Regulates the Expressions of VvIAA9 and VvARF7, Negative Regulators of Fruit Set Initiation, during Parthenocarpic Fruit Development

Science.gov (United States)

Jung, Chan Jin; Hur, Youn Young; Yu, Hee-Ju; Noh, Jung-Ho; Park, Kyo-Sun; Lee, Hee Jae

2014-01-01

Fruit set is initiated only after fertilization and is tightly regulated primarily by gibberellins (GAs) and auxins. The application of either of these hormones induces parthenocarpy, fruit set without fertilization, but the molecular mechanism underlying this induction is poorly understood. In the present study, we have shown that the parthenocarpic fruits induced by GA application at pre-bloom result from the interaction of GA with auxin signaling. The transcriptional levels of the putative negative regulators of fruit set initiation, including Vitis auxin/indole-3-acetic acid transcription factor 9 (VvIAA9), Vitis auxin response factor 7 (VvARF7), and VvARF8 were monitored during inflorescence development in seeded diploid ‘Tamnara’ grapevines with or without GA application. Without GA application, VvIAA9, VvARF7, and VvARF8 were expressed at a relatively high level before full bloom, but decreased thereafter following pollination. After GA application at 14 days before full bloom (DBF); however, the expression levels of VvIAA9 and VvARF7 declined at 5 DBF prior to pollination. The effects of GA application on auxin levels or auxin signaling were also analyzed by monitoring the expression patterns of auxin biosynthesis genes and auxin-responsive genes with or without GA application. Transcription levels of the auxin biosynthesis genes Vitis anthranilate synthase β subunit (VvASB1-like), Vitis YUCCA2 (VvYUC2), and VvYUC6 were not significantly changed by GA application. However, the expressions of Vitis Gretchen Hagen3.2 (VvGH3.2) and VvGH3.3, auxin-responsive genes, were up-regulated from 2 DBF to full bloom with GA application. Furthermore, the Vitis GA signaling gene, VvDELLA was up-regulated by GA application during 12 DBF to 7 DBF, prior to down-regulation of VvIAA9 and VvARF7. These results suggest that VvIAA9 and VvARF7 are negative regulators of fruit set initiation in grapevines, and GA signaling is integrated with auxin signaling via VvDELLA during

How do non-physician clinicians respond to advanced cancer patients' negative expressions of emotions?

Science.gov (United States)

Alexander, Stewart C; Pollak, Kathryn I; Morgan, Perri A; Strand, Justine; Abernethy, Amy P; Jeffreys, Amy S; Arnold, Robert M; Olsen, Maren; Rodriguez, Keri L; Garrigues, Sarah K; Manusov, Justin R E; Tulsky, James A

2011-01-01

Patients with advanced cancer often experience negative emotion; clinicians' empathic responses can alleviate patient distress. Much is known about how physicians respond to patient emotion; less is known about non-physician clinicians. Given that oncology care is increasingly provided by an interdisciplinary team, it is important to know more about how patients with advanced cancer express emotions to non-physician clinicians (NPCs) and how NPCs respond to those empathic opportunities. We audio recorded conversations between non-physician clinicians and patients with advanced cancer. We analyzed 45 conversations between patients and oncology physician assistants, nurse practitioners, and nurse clinicians in which patients or their loved ones expressed at least one negative emotion to the NPC (i.e., an empathic opportunity). Empathic opportunities were coded three ways: type of emotion (anger, sadness, or fear), severity of emotion (least, moderate, or most severe), and NPC response to emotion (not empathic, on-topic medical response, and empathic response). We identified 103 empathic opportunities presented to 25 different NPCs during 45 visits. Approximately half of the empathic opportunities contained anger (53%), followed by sadness (25%) and fear (21%). The majority of emotions expressed were moderately severe (73%), followed by most severe (16%), and least severe (12%). The severity of emotions presented was not found to be statistically different between types of NPCs. NPCs responded to empathic opportunities with empathic statements 30% of the time. Additionally, 40% of the time, NPCs responded to empathic opportunities with on-topic, medical explanations and 30% of the responses were not empathic. Patients expressed emotional concerns to NPCs typically in the form of anger; most emotions were moderately severe, with no statistical differences among types of NPC. On average, NPCs responded to patient emotion with empathic language only 30% of the time. A

5-FU and ixabepilone modify the microRNA expression profiles in MDA-MB-453 triple-negative breast cancer cells

OpenAIRE

YAO, YONGSHAN; CHEN, SHENGHAN; ZHOU, XIN; XIE, LI; CHEN, AIJUN

2013-01-01

This study aimed to discover new potential mechanisms of chemotherapy with drugs used in the treatment of luminal androgen receptor (LAR)-type triple-negative breast cancer (TNBC). We examined the microRNA (miRNA) expression profiles of LAR-type TNBC in vitro, and explored the variation in miRNA expression profiles in cells when treated with the chemotherapy drugs capecitabine and ixabepilone. The present study revealed that the expression levels of the three antitumor miRNAs, miR-122a, miR-1...

Correlation of circRNAs’ differential expression to negative- positive symptoms of patients with schizophrenia

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Ling-ming KONG

2017-11-01

Full Text Available Objective To explore the correlation of circRNAs' expression level to the negative- and positive symptoms of patients with schizophrenia (SZ. Methods Gene chip screening was performed with the peripheral blood samples from each five of SZ patients and normal controls. Nine circRNAs showing differentiate expression were confirmed, and further verification was done by real-time fluorescence quantitative PCR in 102 SZ patients and 103 normal controls. All the SZ patients were assessed with Positive and Negative Symptom Scale (PANSS. Results It was revealed that the expression levels of circRNA_102101, circRNA_102315, circRNA_104597, circRNA_101835 and circRNA_101836 were significantly down-regulated (P<0.01 or P<0.05, and circRNA_103102 and circRNA_103704 were up-regulated in SZ group (P<0.01. The ΔCT value of circRNA_102101 and circRNA_103102 was positively correlated to the positive symptoms (P<0.01 or P<0.05, and the ΔCT value of circRNA_103704 also showed positive correlation with positive symptoms and general psychopathological symptoms (P<0.01 or P<0.05. The ΔCT values of circRNA_102101, circRNA_103102, circRNA_102315, circRNA_103704 and circRNA_102802 were correlated with thinking disorder (P<0.01 or P<0.05, and the ΔCT values of circRNA_102101, circRNA_103102, circRNA_104597, circRNA_103704 and circRNA_102802 were correlated with the activation (P<0.01 or P<0.05. The ΔCT values of circRNA_102101, circRNA_103102, circRNA_103704 and circRNA_102802 were positively correlated with paranoid (P<0.01 or P<0.05, and of circRNA_102101, circRNA_103102, circRNA_103704 and circRNA_102802 were markedly correlated with assault (P<0.01 or P<0.05. Therefore, circRNA_103704 was chosen into regressive equation of positive symptoms (P<0.01, and circRNA_103704 and circRNA_102315 were chosen into regressive equation of general pathological findings (P<0.01 or P<0.05. Conclusion The expression levels of circRNA_103704 and circRNA_103102 are obviously up

Seeing red; the development of pON.mCherry, a broad-host range constitutive expression plasmid for Gram-negative bacteria.

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Michael J Gebhardt

Full Text Available The development of plasmid-mediated gene expression control in bacteria revolutionized the field of bacteriology. Many of these expression control systems rely on the addition of small molecules, generally metabolites or non-metabolized analogs thereof, to the growth medium to induce expression of the genes of interest. The paradigmatic example of an expression control system is the lac system from Escherichia coli, which typically relies on the Ptac promoter and the Lac repressor, LacI. In many cases, however, constitutive gene expression is desired, and other experimental approaches require the coordinated control of multiple genes. While multiple systems have been developed for use in E. coli and its close relatives, the utility and/or functionality of these tools does not always translate to other species. For example, for the Gram-negative pathogen, Legionella pneumophila, a causative agent of Legionnaires' Disease, the aforementioned Ptac system represents the only well-established expression control system. In order to enhance the tools available to study bacterial gene expression in L. pneumophila, we developed a plasmid, pON.mCherry, which confers constitutive gene expression from a mutagenized LacI binding site. We demonstrate that pON.mCherry neither interferes with other plasmids harboring an intact LacI-Ptac expression system nor alters the growth of Legionella species during intracellular growth. Furthermore, the broad-host range plasmid backbone of pON.mCherry allows constitutive gene expression in a wide variety of Gram-negative bacterial species, making pON.mCherry a useful tool for the greater research community.

[{sup 18}F]FBEM-Z{sub HER2:342}-Affibody molecule - a new molecular tracer for in vivo monitoring of HER2 expression by positron emission tomography

Energy Technology Data Exchange (ETDEWEB)

Kramer-Marek, Gabriela; Lee, Sang Bong; Capala, Jacek [National Institutes of Health, National Cancer Institute, Bethesda, MD (United States); Kiesewetter, Dale O.; Jagoda, Elaine [National Institutes of Health, National Institute of Biomedical Imaging and Bioengineering, Bethesda, MD (United States); Martiniova, Lucia [National Institutes of Health, National Institute of Child Health and Human Development, Bethesda, MD (United States)

2008-05-15

The expression of human epidermal growth factor receptor-2 (HER2) receptors in cancers is correlated with a poor prognosis. If assessed in vivo, it could be used for selection of appropriate therapy for individual patients and for monitoring of the tumor response to targeted therapies. We have radiolabeled a HER2-binding Affibody molecule with fluorine-18 for in vivo monitoring of the HER2 expression by positron emission tomography (PET). The HER2-binding Z{sub HER2:342}-Cys Affibody molecule was conjugated with N-2-(4-[{sup 18}F]fluorobenzamido)ethylmaleimide ([{sup 18}F]FBEM). The in vitro binding of the resulting radioconjugate was characterized by receptor saturation and competition assays. For in vivo studies, the radioconjugate was injected into the tail vein of mice bearing subcutaneous HER2-positive or HER2-negative tumors. Some of the mice were pre-treated with non-labeled Z{sub HER2:342}-Cys. The animals were sacrificed at different times post-injection, and the radioactivity in selected tissues was measured. PET images were obtained using an animal PET scanner. In vitro experiments indicated specific, high-affinity binding to HER2. PET imaging revealed a high accumulation of the radioactivity in the tumor as early as 20 min after injection, with a plateau being reached after 60 min. These results were confirmed by biodistribution studies demonstrating that, as early as 1 h post-injection, the tumor to blood concentration ratio was 7.5 and increased to 27 at 4 h. Pre-saturation of the receptors with unlabeled Z{sub HER2:342}-Cys lowered the accumulation of radioactivity in HER2-positive tumors to the levels observed in HER2-negative ones. Our results suggest that the [{sup 18}F]FBEM-Z{sub HER2:342} radioconjugate can be used to assess HER2 expression in vivo. (orig.)

Development of a Laser-based Emittance Monitor for Negative Hydrogen Beams

CERN Document Server

AUTHOR|(CDS)2078368; Schmauss, Bernhard; Gibson, Stephen; Boorman, Gary; Bosco, Alessio

High energy particle accelerators are designed to collide charged particle beams and thus study the collision products. Maximising the collision rate, to generate sufficient statistics for precise measurements of rare processes, is one of the key parameters for optimising the overall collider performance. The CERN Large Hadron Collider (LHC) Injectors Upgrade (LIU) includes the construction of LINAC4, a completely new machine working as a first linear acceleration stage for the LHC beam. By accelerating a negative hydrogen beam (H-) instead of protons, it aims to double the beam brightness via a more efficient transfer to the first circular accelerator and subsequently boost the LHC collision rate. To achieve this, a precise knowledge of the transverse beam characteristics in terms of beam emittance is essential. This thesis work covers the development of a laser-based monitor meant to measure non-destructively the LINAC4 beam transverse profile and emittance. This included the implementation of dif...

Early prostate cancer antigen expression in predicting presence of prostate cancer in men with histologically negative biopsies.

Science.gov (United States)

Hansel, D E; DeMarzo, A M; Platz, E A; Jadallah, S; Hicks, J; Epstein, J I; Partin, A W; Netto, G J

2007-05-01

Early prostate cancer antigen is a nuclear matrix protein that was recently shown to be expressed in prostate adenocarcinoma and adjacent benign tissue. Previous studies have demonstrated early prostate cancer antigen expression in benign prostate tissue up to 5 years before a diagnosis of prostate carcinoma, suggesting that early prostate cancer antigen could be used as a potential predictive marker. We evaluated early prostate cancer antigen expression by immunohistochemistry using a polyclonal antibody (Onconome Inc., Seattle, Washington) on benign biopsies from 98 patients. Biopsies were obtained from 4 groups that included 39 patients with first time negative biopsy (group 1), 24 patients with persistently negative biopsies (group 2), 8 patients with initially negative biopsies who were subsequently diagnosed with prostate carcinoma (group 3) and negative biopsies obtained from 27 cases where other concurrent biopsies contained prostate carcinoma (group 4). Early prostate cancer antigen staining was assessed by 2 of the authors who were blind to the group of the examined sections. Staining intensity (range 0 to 3) and extent (range 1 to 3) scores were assigned. The presence of intensity 3 staining in any of the blocks of a biopsy specimen was considered as positive for early prostate cancer antigen for the primary outcome in the statistical analysis. In addition, as secondary outcomes we evaluated the data using the proportion of blocks with intensity 3 early prostate cancer antigen staining, the mean of the product of staining intensity and staining extent of all blocks within a biopsy, and the mean of the product of intensity 3 staining and extent. Primary outcome analysis revealed the proportion of early prostate cancer antigen positivity to be highest in group 3 (6 of 8, 75%) and lowest in group 2 (7 of 24, 29%, p=0.04 for differences among groups). A relatively higher than expected proportion of early prostate cancer antigen positivity was present in

The cellular prion protein negatively regulates phagocytosis and cytokine expression in murine bone marrow-derived macrophages.

Directory of Open Access Journals (Sweden)

Min Wang

Full Text Available The cellular prion protein (PrP(C is a glycosylphosphatidylinositol (GPI-anchored glycoprotein on the cell surface. Previous studies have demonstrated contradictory roles for PrP(C in connection with the phagocytic ability of macrophages. In the present work, we investigated the function of PrP(C in phagocytosis and cytokine expression in bone marrow-derived macrophages infected with Escherichia coli. E. coli infection induced an increase in the PRNP mRNA level. Knockout of PrP(C promoted bacterial uptake; upregulated Rab5, Rab7, and Eea1 mRNA expression; and increased the recruitment of lysosomal-associated membrane protein-2 to phagosomes, suggesting enhanced microbicidal activity. Remarkably, knockout of PrP(C suppressed the proliferation of internalized bacteria and increased the expression of cytokines such as interleukin-1β. Collectively, our data reveal an important role of PrP(C as a negative regulator for phagocytosis, phagosome maturation, cytokine expression, and macrophage microbicidal activity.

Nanobarcode gene expression monitoring system for potential miniaturized space applications

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Ruan, Weiming; Eastman, P. Scott; Cooke, Patrick A.; Park, Jennifer S.; Chu, Julia S. F.; Gray, Joe W.; Li, Song; Chen, Fanqing Frank

Manned mission to space has been threatened by various cosmos risks including radiation, mirogravity, vacuum, confinement, etc., which may cause genetic variations of astronauts and eventually lead to damages of their health. Thus, the development of small biomedical devices, which can monitor astronaut gene expression changes, is useful for future long-term space missions. Using magnetic microbeads packed with nanocrystal quantum dots at controlled ratios, we were able to generate highly multiplexed nanobarcodes, which can encode a flexible panel of genes. Also, by using a reporter quantum dot, this nanobarcode platform can monitor and quantify gene expression level with improved speed and sensitivity. As a comparison, we studied TGF-β1 induced transcription changes in human bone marrow mesenchymal stem cells with both the nanobarcode microbead system and the Affymetrix GeneChip ® HTA system, which is currently considered as the industrial standard. Though using only 1/20 of the sample RNA, the nanobarcode system showed sensitivity equivalent to Affymetrix GeneChip ® system. The coefficient of variation, dynamic range, and accuracy of the nanobarcodes measurement is equivalent to that of the GeneChip ® HTA system. Therefore, this newly invented nanobarcode microbead platform is thought to be sensitive, flexible, cost-effective and accurate in a level equivalent to the conventional methods. As an extension of the use of this new platform, spacecrafts may carry this miniaturized system as a diagnostic tool for the astronauts.

PD-L1 expression in EBV-negative diffuse large B-cell lymphoma: clinicopathologic features and prognostic implications.

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Xing, Wei; Dresser, Karen; Zhang, Rui; Evens, Andrew M; Yu, Hongbo; Woda, Bruce A; Chen, Benjamin J

2016-09-13

Programmed cell death ligand 1 (PD-L1) is a cell surface glycoprotein that regulates the cellular immune response and serves as a targetable immune checkpoint molecule. PD-L1 is expressed on tumor cells and the immune microenvironment of several human malignancies, including a subset of aggressive lymphomas. We sought to investigate further the clinical and pathologic features of EBV-negative diffuse large B-cell lymphoma (DLBCL) cases that express PD-L1. Immunohistochemical staining using an anti-PD-L1 monoclonal antibody was performed on DLBCL cases from 86 patients. These patients received standard chemotherapy treatment and were followed for up to 175 months. Overall, 14 cases (16%) were considered positive for PD-L1 in tumor cells. In comparison with PD-L1 negative cases, PD-L1 positive cases had a higher rate of non-GCB type (71% vs. 30%, P=0.0060), and higher Ann Arbor stage (II-IV) (100% vs. 73%, P=0.0327). No significant differences were seen in the immunohistochemical expression of BCL2, MYC, or Ki67. Patients with tumors expressing PD-L1 demonstrated inferior overall survival (OS) upon long term follow up (P=0.0447). Both age/sex-adjusted and multivariate analyses identified PD-L1 as an independent predictor for OS (P=0.0101 and P=0.0424). There was no significant difference, however, in terms of remission rates after first treatment, relapse rates, and progression free survival between the groups. Identification of DLBCL cases that express PD-L1 may serve to select a subset of patients that could further benefit from targeted immunotherapy.

A rapid screening method to monitor expression of various recombinant proteins from prokaryotic and eukaryotic expression systems using MALDI-TOF mass spectrometry

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Jebanathirajah, J.A.; Andersen, S.; Blagoev, B.

2002-01-01

Rapid methods using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry to monitor recombinant protein expression from various prokaryotic and eukaryotic cell culture systems were devised. Intracellular as well as secreted proteins from both induced and constitutive...

Critical role of types 2 and 3 deiodinases in the negative regulation of gene expression by T₃in the mouse cerebral cortex.

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Hernandez, Arturo; Morte, Beatriz; Belinchón, Mónica M; Ceballos, Ainhoa; Bernal, Juan

2012-06-01

Thyroid hormones regulate brain development and function through the control of gene expression, mediated by binding of T(3) to nuclear receptors. Brain T(3) concentration is tightly controlled by homeostatic mechanisms regulating transport and metabolism of T(4) and T(3). We have examined the role of the inactivating enzyme type 3 deiodinase (D3) in the regulation of 43 thyroid hormone-dependent genes in the cerebral cortex of 30-d-old mice. D3 inactivation increased slightly the expression of two of 22 positively regulated genes and significantly decreased the expression of seven of 21 negatively regulated genes. Administration of high doses of T(3) led to significant changes in the expression of 12 positive genes and three negative genes in wild-type mice. The response to T(3) treatment was enhanced in D3-deficient mice, both in the number of genes and in the amplitude of the response, demonstrating the role of D3 in modulating T(3) action. Comparison of the effects on gene expression observed in D3 deficiency with those in hypothyroidism, hyperthyroidism, and type 2 deiodinase (D2) deficiency revealed that the negative genes are more sensitive to D2 and D3 deficiencies than the positive genes. This observation indicates that, in normal physiological conditions, D2 and D3 play critical roles in maintaining local T(3) concentrations within a very narrow range. It also suggests that negatively and positively regulated genes do not have the same physiological significance or that their regulation by thyroid hormone obeys different paradigms at the molecular or cellular levels.

Non-negative Tensor Factorization with missing data for the modeling of gene expressions in the Human Brain

DEFF Research Database (Denmark)

Nielsen, Søren Føns Vind; Mørup, Morten

2014-01-01

Non-negative Tensor Factorization (NTF) has become a prominent tool for analyzing high dimensional multi-way structured data. In this paper we set out to analyze gene expression across brain regions in multiple subjects based on data from the Allen Human Brain Atlas [1] with more than 40 % data m...

Loss of PTEN expression is associated with aggressive behavior and poor prognosis in Middle Eastern triple-negative breast cancer.

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Beg, Shaham; Siraj, Abdul K; Prabhakaran, Sarita; Jehan, Zeenath; Ajarim, Dahish; Al-Dayel, Fouad; Tulbah, Asma; Al-Kuraya, Khawla S

2015-06-01

PTEN is a tumor suppressor that negatively regulates the PI3 K-AKT signaling pathway which is involved in the pathogenesis of many different tumor types and serves as a prognostic marker in breast cancer. However, the significance of the role of PTEN in Middle Eastern ethnic breast cancer has not been explored especially with the fact that breast cancer originating from this ethnic population tend to behave more aggressively than breast cancer in the west. In this study, we analyzed PTEN alteration in a tissue microarray format containing more than 1000 primary breast cancers with clinical follow-up data. Tissue Microarray sections were analyzed for protein expression and copy number change using immunohistochemistry and fluorescence in situ hybridization. Loss of PTEN immunostaining was observed in 77 % of the cases. PTEN loss was significantly associated with large tumor size (p = 0.0030), high grade (p = 0.0281), tumor recurrence (p = 0.0333), and triple-negative breast cancers (p = 0.0086). PTEN loss in triple-negative breast cancers was significantly associated with rapid tumor cell proliferation (p = 0.0396) and poor prognosis (p = 0.0408). PTEN deletion was found only in 60 cases (6.4 %). Loss of PTEN protein expression occurs at high frequency in Middle Eastern breast cancer. PTEN inactivation may potentially lead to an aggressive behavior of tumor cells through stimulation of tumor cell proliferation. Furthermore, PTEN signaling pathway might be used as potential therapeutic target in triple-negative breast cancers since loss of its expression is shown to be significantly associated with this aggressive subtype of breast cancer.

Negative-Pressure Hydrocephalus: A Case Report on Successful Treatment Under Intracranial Pressure Monitoring with Bilateral Ventriculoperitoneal Shunts.

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Pandey, Sajan; Jin, Yi; Gao, Liang; Zhou, Cheng Cheng; Cui, Da Ming

2017-03-01

Negative-pressure hydrocephalus (NegPH), a very rare condition of unknown etiology and optimal treatment, usually presents postneurosurgery with clinical and imaging features of hydrocephalus, but with negative cerebrospinal fluid pressure. We describe a NegPH case of -3 mm Hg intracranial pressure that was successfully treated to achieve 5 mm Hg under continuous intracranial pressure monitoring with horizontal positioning, head down and legs elevated to 10°-15°, neck wrapping for controlled venous drainage, chest and abdomen bandages, infusion of 5% dextrose fluid to lower plasma osmolarity (Na + , 130-135 mmol/L), daily cerebrospinal fluid drainage >200 mL, and arterial blood gas partial pressure of carbon dioxide >40 mm Hg. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of Negative Pressure on Proliferation, Virulence Factor Secretion, Biofilm Formation, and Virulence-Regulated Gene Expression of Pseudomonas aeruginosa In Vitro

Directory of Open Access Journals (Sweden)

Guo-Qi Wang

2016-01-01

Full Text Available Objective. To investigate the effect of negative pressure conditions induced by NPWT on P. aeruginosa. Methods. P. aeruginosa was cultured in a Luria–Bertani medium at negative pressure of −125 mmHg for 24 h in the experimental group and at atmospheric pressure in the control group. The diameters of the colonies of P. aeruginosa were measured after 24 h. ELISA kit, orcinol method, and elastin-Congo red assay were used to quantify the virulence factors. Biofilm formation was observed by staining with Alexa Fluor® 647 conjugate of concanavalin A (Con A. Virulence-regulated genes were determined by quantitative RT-PCR. Results. As compared with the control group, growth of P. aeruginosa was inhibited by negative pressure. The colony size under negative pressure was significantly smaller in the experimental group than that in the controls (p<0.01. Besides, reductions in the total amount of virulence factors were observed in the negative pressure group, including exotoxin A, rhamnolipid, and elastase. RT-PCR results revealed a significant inhibition in the expression level of virulence-regulated genes. Conclusion. Negative pressure could significantly inhibit the growth of P. aeruginosa. It led to a decrease in the virulence factor secretion, biofilm formation, and a reduction in the expression level of virulence-regulated genes.

Expression of the hypoxia-inducible monocarboxylate transporter MCT4 is increased in triple negative breast cancer and correlates independently with clinical outcome

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Doyen, J. [Department of Radiation Oncology, Centre A. Lacassagne, Nice (France); Trastour, C. [Department of Gynecology, Archet II Hospital, 06202 Nice (France); Ettore, F.; Peyrottes, I.; Toussant, N. [Department of Pathology, Centre A. Lacassagne, Nice (France); Gal, J. [Department of Medical Statistics, Centre A. Lacassagne, Nice (France); Ilc, K.; Roux, D. [Institute for Research on Cancer and Aging (IRCAN), University of Nice, Centre A. Lacassagne, 06189 Nice (France); Parks, S.K. [Centre Scientifique de Monaco (CSM) (Monaco); Ferrero, J.M. [Department of Medical Oncology, Centre A. Lacassagne, Nice (France); Pouysségur, J., E-mail: jacques.pouyssegur@unice.fr [Institute for Research on Cancer and Aging (IRCAN), University of Nice, Centre A. Lacassagne, 06189 Nice (France); Centre Scientifique de Monaco (CSM) (Monaco)

2014-08-15

Highlights: • Glycolytic markers are highly expressed in triple negative breast cancers. • Lactate/H{sup +} symporter MCT4 demonstrated the strongest deleterious impact on survival. • MCT4 should serve as a new prognostic factor in node-negative breast cancers. - Abstract: Background: {sup 18}Fluor-deoxy-glucose PET-scanning of glycolytic metabolism is being used for staging in many tumors however its impact on prognosis has never been studied in breast cancer. Methods: Glycolytic and hypoxic markers: glucose transporter (GLUT1), carbonic anhydrase IX (CAIX), monocarboxylate transporter 1 and 4 (MCT1, 4), MCT accessory protein basigin and lactate-dehydrogenase A (LDH-A) were assessed by immunohistochemistry in two cohorts of breast cancer comprising 643 node-negative and 127 triple negative breast cancers (TNBC) respectively. Results: In the 643 node-negative breast tumor cohort with a median follow-up of 124 months, TNBC were the most glycolytic (≈70%), followed by Her-2 (≈50%) and RH-positive cancers (≈30%). Tumoral MCT4 staining (without stromal staining) was a strong independent prognostic factor for metastasis-free survival (HR = 0.47, P = 0.02) and overall-survival (HR = 0.38, P = 0.002). These results were confirmed in the independent cohort of 127 cancer patients. Conclusion: Glycolytic markers are expressed in all breast tumors with highest expression occurring in TNBC. MCT4, the hypoxia-inducible lactate/H{sup +} symporter demonstrated the strongest deleterious impact on survival. We propose that MCT4 serves as a new prognostic factor in node-negative breast cancer and can perhaps act soon as a theranostic factor considering the current pharmacological development of MCT4 inhibitors.

Associations Between Exposure to and Expression of Negative Opinions About Human Papillomavirus Vaccines on Social Media: An Observational Study.

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Dunn, Adam G; Leask, Julie; Zhou, Xujuan; Mandl, Kenneth D; Coiera, Enrico

2015-06-10

Groups and individuals that seek to negatively influence public opinion about the safety and value of vaccination are active in online and social media and may influence decision making within some communities. We sought to measure whether exposure to negative opinions about human papillomavirus (HPV) vaccines in Twitter communities is associated with the subsequent expression of negative opinions by explicitly measuring potential information exposure over the social structure of Twitter communities. We hypothesized that prior exposure to opinions rejecting the safety or value of HPV vaccines would be associated with an increased risk of posting similar opinions and tested this hypothesis by analyzing temporal sequences of messages posted on Twitter (tweets). The study design was a retrospective analysis of tweets related to HPV vaccines and the social connections between users. Between October 2013 and April 2014, we collected 83,551 English-language tweets that included terms related to HPV vaccines and the 957,865 social connections among 30,621 users posting or reposting the tweets. Tweets were classified as expressing negative or neutral/positive opinions using a machine learning classifier previously trained on a manually labeled sample. During the 6-month period, 25.13% (20,994/83,551) of tweets were classified as negative; among the 30,621 users that tweeted about HPV vaccines, 9046 (29.54%) were exposed to a majority of negative tweets. The likelihood of a user posting a negative tweet after exposure to a majority of negative opinions was 37.78% (2780/7361) compared to 10.92% (1234/11,296) for users who were exposed to a majority of positive and neutral tweets corresponding to a relative risk of 3.46 (95% CI 3.25-3.67, Prelation to HPV vaccines. We found that among users that tweeted about HPV vaccines, those who were more often exposed to negative opinions were more likely to subsequently post negative opinions. Although this research may be useful for

The Role of Monitoring Gentamicin Levels in Patients with Gram-Negative Peritoneal Dialysis-Associated Peritonitis

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Tang, Wen; Cho, Yeoungjee; Hawley, Carmel M.; Badve, Sunil V.; Johnson, David W.

2014-01-01

♦ Background: There is limited available evidence regarding the role of monitoring serum gentamicin concentrations in peritoneal dialysis (PD) patients receiving this antimicrobial agent in gram-negative PD-associated peritonitis. ♦ Methods: Using data collected in all patients receiving PD at a single center who experienced a gram-negative peritonitis episode between 1 January 2005 and 31 December 2011, we investigated the relationship between measured serum gentamicin levels on day 2 following initial empiric antibiotic therapy and subsequent clinical outcomes of confirmed gram-negative peritonitis. ♦ Results: Serum gentamicin levels were performed on day 2 in 51 (77%) of 66 first gram-negative peritonitis episodes. Average serum gentamicin levels on day 2 were 1.83 ± 0.84 mg/L with levels exceeding 2 mg/L in 22 (43%) cases. The overall cure rate was 64%. No cases of ototoxicity were observed. Day-2 gentamicin levels were not significantly different between patients who did and did not have a complication or cure. Using multivariable logistic regression analysis, failure to cure peritonitis was not associated with either day-2 gentamicin level (adjusted odds ratio (OR) 0.96, 95% confidence interval (CI) 0.25 - 3.73) or continuation of gentamicin therapy beyond day 2 (OR 0.28, 0.02 - 3.56). The only exception was polymicrobial peritonitis, where day-2 gentamicin levels were significantly higher in episodes that were cured (2.06 ± 0.41 vs 1.29 ± 0.71, p = 0.01). In 17 (26%) patients receiving extended gentamicin therapy, day-5 gentamicin levels were not significantly related to peritonitis cure. ♦ Conclusion: Day-2 gentamicin levels did not predict gentamicin-related harm or efficacy during short-course gentamicin therapy for gram-negative PD-related peritonitis, except in cases of polymicrobial peritonitis, where higher levels were associated with cure. PMID:24385334

Equanimity to Excess: Inhibiting the Expression of Negative Emotion is Associated with Depression Symptoms in Girls

OpenAIRE

Keenan, Kate; Hipwell, Alison; Hinze, Amanda; Babinski, Dara

2009-01-01

Emotion dysregulation is often invoked as an important construct for understanding risk for psychopathology, but specificity of domains of emotion regulation in clinically relevant research is often lacking. In the present study Gross’ (2001) model of emotion regulation is used to generate hypotheses regarding the relative contribution of two specific types of deficits in emotion regulation, inhibited and disinhibited expression of negative emotion, to individual differences in depressive sym...

Effects of Cultural Tightness-Looseness and Social Network Density on Expression of Positive and Negative Emotions: A Large-Scale Study of Impression Management by Facebook Users.

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Liu, Pan; Chan, David; Qiu, Lin; Tov, William; Tong, Victor Joo Chuan

2018-05-01

Using data from 13,789 Facebook users across U.S. states, this study examined the main effects of societal-level cultural tightness-looseness and its interaction effects with individuals' social network density on impression management (IM) in terms of online emotional expression. Results showed that individuals from culturally tight (vs. loose) states were more likely to express positive emotions and less likely to express negative emotions. Meanwhile, for positive emotional expression, there was a tightness-looseness by social network density interaction effect. In culturally tight states, individuals with dense (vs. sparse) networks were more likely to express positive emotions, while in culturally loose states this pattern was reversed. For negative emotional expression, however, no such interaction was observed. Our findings highlight the influence of cultural norms and social network structure on emotional expressions as IM strategies.

Elongated Hypocotyl 5-Homolog (HYH Negatively Regulates Expression of the Ambient Temperature-Responsive MicroRNA Gene MIR169

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Phanu T. Serivichyaswat

2017-12-01

Full Text Available Arabidopsis microRNA169 (miR169 is an ambient temperature-responsive microRNA that plays an important role in stress responses and the floral transition. However, the transcription factors that regulate the expression of MIR169 have remained unknown. In this study, we show that Elongated Hypocotyl 5-Homolog (HYH directly binds to the promoter of MIR169a and negatively regulates its expression. Absolute quantification identified MIR169a as the major locus producing miR169. GUS reporter assays revealed that the deletion of a 498-bp fragment (–1,505 to –1,007, relative to the major transcriptional start site of MIR169a abolished its ambient temperature-responsive expression. DNA-affinity chromatography followed by liquid chromatography-mass spectrometry analysis identified transcription factor HYH as a trans-acting factor that binds to the 498-bp promoter fragment of pri-miR169a. Electrophoretic mobility shift assays and chromatin immunoprecipitation–quantitative PCR demonstrated that the HYH.2 protein, a predominant isoform of HYH, directly associated with a G-box-like motif in the 498-bp fragment of pri-miR169a. Higher enrichment of HYH.2 protein on the promoter region of MIR169a was seen at 23°C, consistent with the presence of more HYH.2 protein in the cell at the temperature. Transcript levels of pri-miR169a increased in hyh mutants and decreased in transgenic plants overexpressing HYH. Consistent with the negative regulation of MIR169a by HYH, the diurnal levels of HYH mRNA and pri-miR169a showed opposite patterns. Taken together, our results suggest that HYH is a transcription factor that binds to a G-box-like motif in the MIR169a promoter and negatively regulates ambient temperature-responsive expression of MIR169a at higher temperatures in Arabidopsis.

Application of anti-listerial bacteriocins: monitoring enterocin expression by multiplex relative reverse transcription-PCR.

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Williams, D Ross; Chanos, Panagiotis

2012-12-01

Listeriosis is a deadly food-borne disease, and its incidence may be limited through the biotechnological exploitation of a number of anti-listerial biocontrol agents. The most widely used of these agents are bacteriocins and the Class II enterocins are characterized by their activity against Listeria. Enterocins are primarily produced by enterococci, particularly Enterococcus faecium and many strains have been described, often encoding multiple bacteriocins. The use of these strains in food will require that they are free of virulence functions and that they exhibit a high level expression of anti-listerial enterocins in fermentation conditions. Multiplex relative RT (reverse transcription)-PCR is a technique that is useful in the discovery of advantageous expression characteristics among enterocin-producing strains. It allows the levels of individual enterocin gene expression to be monitored and determination of how expression is altered under different growth conditions.

Defective interleukin-4/Stat6 activity correlates with increased constitutive expression of negative regulators SOCS-3, SOCS-7, and CISH in colon cancer cells.

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Liu, Xiao Hong; Xu, Shuang Bing; Yuan, Jia; Li, Ben Hui; Zhang, Yan; Yuan, Qin; Li, Pin Dong; Li, Feng; Zhang, Wen Jie

2009-12-01

Interleukin-4 (IL-4)-induced Stat6 activities (phenotypes) vary among human cancer cells, of which the HT-29 cell line carries an active Stat6(high) phenotype, while Caco-2 carries a defective Stat6(null) phenotype, respectively. Cancer cells with Stat6(high) show resistance to apoptosis and exaggerated metastasis, suggesting the clinical significance of Stat6 phenotypes. We previously showed that Stat6(high) HT-29 cells exhibited low constitutive expression of Stat6-negative regulators SOCS-1 and SHP-1 because of gene hypermethylation. This study further examined the constitutive expression of other closely related SOCS family numbers including SOCS-3, SOCS-5, SOCS-7, and CISH using RT-PCR. Similar to SOCS-1 and SHP-1, Stat6(high) HT-29 cells expressed low constitutive mRNA of SOCS-3, SOCS-7, and CISH than Stat6(null) Caco-2 cells. Interestingly, DNA demethylation using 5-aza-2'-deoxycytidine in HT-29 cells up-regulated mRNA expression of the above genes, indicating a hypermethylation status, which was confirmed by methylation-specific sequencing in selected SOCS-3 gene. Furthermore, defective Stat6(null) Caco-2 exhibited impaired phosphorylation of Stat6 after IL-4 stimulation by flow cytometry, in keeping with the notion of an over-performed negative regulation. The findings that IL-4/Stat6 phenotypes show differential expression of multiple negative regulators suggest a model that a collective force of powerful negative regulators, directly and indirectly, acts on Stat6 activation, which may result in differential Stat6 phenotypes.

Multilevel analysis of facial expressions of emotion and script: self-report (arousal and valence) and psychophysiological correlates

OpenAIRE

Balconi, Michela; Vanutelli, Maria Elide; Finocchiaro, Roberta

2014-01-01

Background The paper explored emotion comprehension in children with regard to facial expression of emotion. The effect of valence and arousal evaluation, of context and of psychophysiological measures was monitored. Indeed subjective evaluation of valence (positive vs. negative) and arousal (high vs. low), and contextual (facial expression vs. facial expression and script) variables were supposed to modulate the psychophysiological responses. Methods Self-report measures (in terms of correct...

Web-based visualisation of head pose and facial expressions changes: monitoring human activity using depth data

OpenAIRE

Kalliatakis, Grigorios; Vidakis, Nikolaos; Triantafyllidis, Georgios

2017-01-01

Despite significant recent advances in the field of head pose estimation and facial expression recognition, raising the cognitive level when analysing human activity presents serious challenges to current concepts. Motivated by the need of generating comprehensible visual representations from different sets of data, we introduce a system capable of monitoring human activity through head pose and facial expression changes, utilising an affordable 3D sensing technology (Microsoft Kinect sensor)...

Electrocortical reactivity to negative and positive facial expressions in individuals with a family history of major depression.

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Watters, Anna J; Harris, Anthony W F; Williams, Leanne M

2018-05-21

Facial expressions signaling threat and mood-congruent loss have been used to probe abnormal neural reactivity in major depressive disorder (MDD) and may be implicated in genetic vulnerability to MDD. This study investigated electro-cortical reactivity to facial expressions 101 unaffected, adult first degree relatives of probands with MDD and non-relative controls (n = 101). We investigated event-related potentials (ERPs) to five facial expressions of basic emotion: fear, anger, disgust, sadness and happiness under both subliminal (masked) and conscious (unmasked) presentation conditions, and the source localization of group differences. In the conscious condition, controls showed a distinctly positive-going shift in responsive to negative versus happy faces, reflected in a greater positivity for the VPP frontally and the P300 parietally, and less negativity for the N200. By contrast, relatives showed less differentiation of emotions, reflected in less VPP and P300 positivity, particularly for anger and disgust, and which produced an enhanced N200 for sadness. These group differences were consistently source localized to the anterior cingulate cortex. The findings contribute new evidence for neural disruptions underlying the differentiation of salient emotions in familial risk for depression. These disruptions occur in the appraisal (∼200 ms post-stimulus) through to the context evaluation (∼300 ms+ post-stimulus) phases of of emotion processing, consistent with theories that risk for depression involves biased or attenuated processing of emotion. Copyright © 2018. Published by Elsevier B.V.

Caveolin-1 expression as a prognostic marker in triple negative breast cancers of Asian women.

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Yeong, Joe; Thike, Aye Aye; Ikeda, Murasaki; Lim, Jeffrey Chun Tatt; Lee, Bernett; Nakamura, Seigo; Iqbal, Jabed; Tan, Puay Hoon

2018-02-01

Triple-negative breast cancers (TNBCs) are defined by their lack of oestrogen receptor, progesterone receptor and epidermal growth factor receptor 2. Although heterogeneous, the majority are aggressive and treatment options are limited. Caveolin acts as tumour suppressor or promoter depending on the cancer type. In this study, we aimed to determine if the expression levels of the candidate biomarker caveolin-1 on stromal or tumour cells were associated with clinicopathological parameters and disease outcomes in TNBCs from an ethnically diverse cohort of Asian women. Tumour specimens from 699 women with TNBC were subjected to immunohistochemical analysis of the frequency and intensity of caveolin-1 expression in tumour and stromal cells. A subset of 141 tumour samples also underwent Nanostring measurement of CAV1 mRNA. Results were correlated with clinicopathological parameters and disease outcomes. Expression of caveolin-1 in stromal cells was observed in 14.4% of TNBC cases. TNBCs of the basal-like phenotype (85% of samples) were significantly more likely to exhibit stromal cell caveolin-1 expression (p=0.028), as were those with a trabecular growth pattern (p=0.007). Lack of stromal caveolin-1 expression in both TNBCs and those with the basal-like phenotype was significantly associated with worse overall survival (p=0.009 and p=0.026, respectively): accordingly, increasing mRNA levels of CAV1 in TNBC samples predicted better overall survival. Caveolin-1 expression on TNBC tumour cells was not associated with clinical outcome. Stromal, but not tumoural, caveolin-1 expression is significantly associated with survival in Asian women with TNBC. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Predictive value of BRCA1/2 mRNA expression for response to neoadjuvant chemotherapy in BRCA-negative breast cancers.

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Xu, Ye; Ouyang, Tao; Li, Jinfeng; Wang, Tianfeng; Fan, Zhaoqing; Fan, Tie; Lin, Benyao; Xie, Yuntao

2018-01-01

It is well known that BRCA1 and BRCA2 play a central role in DNA repair, but the relationship between BRCA1 and BRCA2 mRNA expression and response to neoadjuvant chemotherapy in sporadic breast cancer patients has not been well established. Here, we investigate the association between BRCA1 or BRCA2 mRNA expression levels and pathological response in 674 BRCA1/2 mutation-negative breast cancer patients who received neoadjuvant chemotherapy. BRCA1 and BRCA2 mRNA expression were assessed using quantitative real-time polymerase chain reaction in core biopsy breast cancer tissue obtained prior to the initiation of neoadjuvant chemotherapy. A total 129 patients (19.1%) achieved pathological complete response (pCR) after neoadjuvant chemotherapy. Among patients treated with anthracycline-based chemotherapy (n = 531), BRCA1 mRNA low expression patients had a significantly higher pCR rate than intermediate or high BRCA1 mRNA expression groups (24.6% vs 16.8% or 14.0%, P = .031) and retained borderline significance (OR = 1.54, 95% CI = 0.93-2.56, P = .094) in multivariate analysis. Among the 129 patients who received a taxane-based regimen, pCR rate showed no differences in BRCA1 low, intermediate, and high mRNA level subgroups (19.6%, 26.8% and 21.4%, respectively; P = .71). BRCA2 mRNA level was not associated with pCR rate in the anthracyline-based treated subgroup (P = .60) or the taxane-based regimen subgroup (P = .82). Taken together, our findings suggested that BRCA1 mRNA expression could be used as a predictive marker in BRCA1/2 mutation-negative breast cancer patients who received neoadjuvant anthracycline-based treatment. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Expression of aurora kinase A is associated with metastasis-free survival in node-negative breast cancer patients

International Nuclear Information System (INIS)

Siggelkow, Wulf; Koelbl, Heinz; Gehrmann, Mathias; Marchan, Rosemarie; Cadenas, Cristina; Hengstler, Jan G; Schmidt, Marcus; Boehm, Daniel; Gebhard, Susanne; Battista, Marco; Sicking, Isabel; Lebrecht, Antje; Solbach, Christine; Hellwig, Birte; Rahnenführer, Jörg

2012-01-01

Inhibitors targeting the cell cycle-regulated aurora kinase A (AURKA) are currently being developed. Here, we examine the prognostic impact of AURKA in node-negative breast cancer patients without adjuvant systemic therapy (n = 766). AURKA was analyzed using microarray-based gene-expression data from three independent cohorts of node-negative breast cancer patients. In multivariate Cox analyses, the prognostic impact of age, histological grade, tumor size, estrogen receptor (ER), and HER2 were considered. Patients with higher AURKA expression had a shorter metastasis-free survival (MFS) in the Mainz (HR 1.93; 95% CI 1.34 – 2.78; P < 0.001), Rotterdam (HR 1.95; 95% CI 1.45– 2.63; P<0.001) and Transbig (HR 1.52; 95% CI 1.14–2.04; P=0.005) cohorts. AURKA was also associated with MFS in the molecular subtype ER+/HER2- carcinomas (HR 2.10; 95% CI 1.70–2.59; P<0.001), but not in ER-/HER2- nor in HER2+ carcinomas. In the multivariate Cox regression adjusted to age, grade and tumor size, AURKA showed independent prognostic significance in the ER+/HER2- subtype (HR 1.73; 95% CI 1.24–2.42; P=0.001). Prognosis of patients in the highest quartile of AURKA expression was particularly poor. In addition, AURKA correlated with the proliferation metagene (R=0.880; P<0.001), showed a positive association with grade (P<0.001), tumor size (P<0.001) and HER2 (P<0.001), and was inversely associated with ER status (P<0.001). AURKA is associated with worse prognosis in estrogen receptor positive breast carcinomas. Patients with the highest AURKA expression (>75% percentile) have a particularly bad prognosis and may profit from therapy with AURKA inhibitors

Keratin-6 driven ODC expression to hair follicle keratinocytes enhances stemness and tumorigenesis by negatively regulating Notch

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Arumugam, Aadithya; Weng, Zhiping; Chaudhary, Sandeep C.; Afaq, Farrukh [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294-0019 (United States); Elmets, Craig A. [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294-0019 (United States); Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294-0019 (United States); Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL 35294 (United States)

2014-08-29

Highlights: • Targeting ODC to hair follicle augments skin carcinogenesis and invasive SCCs. • Hair follicle ODC expands stem cell compartment carrying CD34{sup +}/K15{sup +}/p63{sup +} keratinocytes. • Negatively regulated Notch1 is associated with expansion of stem cell compartment. - Abstract: Over-expression of ornithine decarboxylase (ODC) is known to be involved in the epidermal carcinogenesis. However, the mechanism by which it enhances skin carcinogenesis remains undefined. Recently, role of stem cells localized in various epidermal compartments has been shown in the pathogenesis of skin cancer. To direct ODC expression in distinct epidermal compartments, we have developed keratin 6 (K6)-ODC/SKH-1 and keratin 14 (K14)-ODC/SKH-1 mice and employed them to investigate the role of ODC directed to these epidermal compartments on UVB-induced carcinogenesis. K6-driven ODC over-expression directed to outer root sheath (ORS) of hair follicle was more effective in augmenting tumorigenesis as compared to mice where K14-driven ODC expression was directed to inter-follicular epidermal keratinocytes. Chronically UVB-irradiated K6-ODC/SKH-1 developed 15 ± 2.5 tumors/mouse whereas K14-ODC/SKH-1 developed only 6.8 ± 1.5 tumors/mouse. K6-ODC/SKH-1 showed augmented UVB-induced proliferation and much higher pro-inflammatory responses than K14-ODC/SKH-1 mice. Tumors induced in K6-ODC/SKH-1 were rapidly growing, invasive and ulcerative squamous cell carcinoma (SCC) showing decreased expression of epidermal polarity marker E-cadherin and enhanced mesenchymal marker, fibronectin. Interestingly, the number of CD34/CK15/p63 positive stem-like cells was significantly higher in chronically UVB-irradiated K6-ODC/SKH-1 as compared to K14-ODC/SKH-1 mice. Reduced Notch1 expression was correlated with the expansion of stem cell compartment in these animals. However, other signaling pathways such as DNA damage response or mTOR signaling pathways were not significantly different in

Keratin-6 driven ODC expression to hair follicle keratinocytes enhances stemness and tumorigenesis by negatively regulating Notch

International Nuclear Information System (INIS)

Arumugam, Aadithya; Weng, Zhiping; Chaudhary, Sandeep C.; Afaq, Farrukh; Elmets, Craig A.; Athar, Mohammad

2014-01-01

Highlights: • Targeting ODC to hair follicle augments skin carcinogenesis and invasive SCCs. • Hair follicle ODC expands stem cell compartment carrying CD34 + /K15 + /p63 + keratinocytes. • Negatively regulated Notch1 is associated with expansion of stem cell compartment. - Abstract: Over-expression of ornithine decarboxylase (ODC) is known to be involved in the epidermal carcinogenesis. However, the mechanism by which it enhances skin carcinogenesis remains undefined. Recently, role of stem cells localized in various epidermal compartments has been shown in the pathogenesis of skin cancer. To direct ODC expression in distinct epidermal compartments, we have developed keratin 6 (K6)-ODC/SKH-1 and keratin 14 (K14)-ODC/SKH-1 mice and employed them to investigate the role of ODC directed to these epidermal compartments on UVB-induced carcinogenesis. K6-driven ODC over-expression directed to outer root sheath (ORS) of hair follicle was more effective in augmenting tumorigenesis as compared to mice where K14-driven ODC expression was directed to inter-follicular epidermal keratinocytes. Chronically UVB-irradiated K6-ODC/SKH-1 developed 15 ± 2.5 tumors/mouse whereas K14-ODC/SKH-1 developed only 6.8 ± 1.5 tumors/mouse. K6-ODC/SKH-1 showed augmented UVB-induced proliferation and much higher pro-inflammatory responses than K14-ODC/SKH-1 mice. Tumors induced in K6-ODC/SKH-1 were rapidly growing, invasive and ulcerative squamous cell carcinoma (SCC) showing decreased expression of epidermal polarity marker E-cadherin and enhanced mesenchymal marker, fibronectin. Interestingly, the number of CD34/CK15/p63 positive stem-like cells was significantly higher in chronically UVB-irradiated K6-ODC/SKH-1 as compared to K14-ODC/SKH-1 mice. Reduced Notch1 expression was correlated with the expansion of stem cell compartment in these animals. However, other signaling pathways such as DNA damage response or mTOR signaling pathways were not significantly different in tumors induced

Novel stimuli are negative stimuli: evidence that negative affect is reduced in the mere exposure effect.

Science.gov (United States)

Robinson, Brent M; Elias, Lorin J

2005-04-01

Repeated exposure of a nonreinforced stimulus results in an increased preference for that stimulus, the mere exposure effect. The present study repeatedly presented positive, negative, and neutrally affective faces to 48 participants while they made judgments about the emotional expression. Participants then rated the likeability of novel neutrally expressive faces and some of these previously presented faces, this time in their neutral expression. Faces originally presented as happy were rated as the most likeable, followed by faces originally presented as neutral. Negative and novel faces were not rated significantly differently from each other. These findings support the notion that the increase in preference towards repeatedly presented stimuli is the result of the reduction in negative affect, consistent with the modified two-factor uncertainty-reduction model and classical conditioning model of the mere exposure effect.

Evidence for the negative regulation of phytase gene expression in Streptomyces lividans and Streptomyces coelicolor.

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Boukhris, Ines; Dulermo, Thierry; Chouayekh, Hichem; Virolle, Marie-Joëlle

2016-01-01

Sco7697, a gene encoding a phytase, enzyme able to degrade phytate (myo-inositol 1,2,3,4,5,6-hexakis phosphate), the most abundant phosphorus storing compound in plants is present in the genome of S. coelicolor, a soil born bacteria with a saprophytic lifestyle. The expression of this gene was previously shown to be induced in conditions of Pi limitation by the response regulator PhoP binding to an operator sequence, the PHO box, located upstream of the -35 promoter sequence. A close examination of the promoter region of sco7697 revealed the presence of another putative operator site, a Direct Repeat (DR), located downstream of the -10 promoter sequence. In order to determine whether this DR played a role in regulation of sco7697 expression, different variants of the phytase gene promoter region were transcriptionally fused to the ß-glucuronidase reporter gene (GUS). As expected, deletion of the PHO box led to abolition of sco7697 induction in conditions of Pi limitation. Interestingly, alteration of the DR correlated with a dramatic increase of GUS expression but only when PhoP was present. These results demonstrated that this DR is the site of strong negative regulation by an unknown repressor. The latter would impede the necessary activation of phytase expression by PhoP. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pacific white shrimp (Litopenaeus vannamei) vitellogenesis-inhibiting hormone (VIH) is predominantly expressed in the brain and negatively regulates hepatopancreatic vitellogenin (VTG) gene expression.

Science.gov (United States)

Chen, Ting; Zhang, Lv-Ping; Wong, Nai-Kei; Zhong, Ming; Ren, Chun-Hua; Hu, Chao-Qun

2014-03-01

Ovarian maturation in crustaceans is temporally orchestrated by two processes: oogenesis and vitellogenesis. The peptide hormone vitellogenesis-inhibiting hormone (VIH), by far the most potent negative regulator of crustacean reproduction known, critically modulates crustacean ovarian maturation by suppressing vitellogenin (VTG) synthesis. In this study, cDNA encoding VIH was cloned from the eyestalk of Pacific white shrimp, Litopenaeus vannamei, a highly significant commercial culture species. Phylogenetic analysis suggests that L. vannamei VIH (lvVIH) can be classified as a member of the type II crustacean hyperglycemic hormone family. Northern blot and RT-PCR results reveal that both the brain and eyestalk were the major sources for lvVIH mRNA expression. In in vitro experiments on primary culture of shrimp hepatopancreatic cells, it was confirmed that some endogenous inhibitory factors existed in L. vannamei hemolymph, brain, and eyestalk that suppressed hepatopancreatic VTG gene expression. Purified recombinant lvVIH protein was effective in inhibiting VTG mRNA expression in both in vitro primary hepatopancreatic cell culture and in vivo injection experiments. Injection of recombinant VIH could also reverse ovarian growth induced by eyestalk ablation. Furthermore, unilateral eyestalk ablation reduced the mRNA level of lvVIH in the brain but not in the remaining contralateral eyestalk. Our study, as a whole, provides new insights on VIH regulation of shrimp reproduction: 1) the brain and eyestalk are both important sites of VIH expression and therefore possible coregulators of hepatopancreatic VTG mRNA expression and 2) eyestalk ablation could increase hepatopancreatic VTG expression by transcriptionally abolishing eyestalk-derived VIH and diminishing brain-derived VIH.

Mammary gene expression profiles during an intramammary challenge reveal potential mechanisms linking negative energy balance with impaired immune response

DEFF Research Database (Denmark)

Moyes, Kasey; Drackley, J K; Morin, D E

2010-01-01

Our objective was to compare mammary tissue gene expression profiles during a Streptococcus uberis (S. uberis) mastitis challenge between lactating cows subjected to dietary-induced negative energy balance (NEB; n = 5) and cows fed ad libitum to maintain positive energy balance (PEB; n = 5...... 0.05), with 86 DEG up-regulated and 201 DEG down-regulated. Canonical pathways most affected by NEB were IL-8 Signaling (10 genes), Glucocorticoid Receptor Signaling (13), and NRF2-mediated Oxidative Stress Response (10). Among genes differentially expressed by NEB, Cell Growth and Proliferation (48...

Value of post-operative reassessment of estrogen receptor α expression following neoadjuvant chemotherapy with or without gefitinib for estrogen receptor negative breast cancer

DEFF Research Database (Denmark)

Bernsdorf, Mogens; Balslev, Eva; Lykkesfeldt, Anne

2011-01-01

The NICE trial was designed to evaluate the possible benefits of adding epidermal growth factor receptor targeted therapy to neoadjuvant chemotherapy in patients with estrogen receptor α (ER) negative and operable breast cancer. Preclinical data have suggested that signalling through the Erb......B receptors or downstream effectors may repress ER expression. Here the authors investigated whether gefitinib, given neoadjuvant in combination with epirubicin and cyclophosphamide (EC), could restore ER expression. Eligible patients in the NICE trial were women with unilateral, primary operable, ER negative...... to positive. A change was seen in three patients in the gefitinib (5.1%) and in two patients in the placebo (3.6%) group with a difference of 1.51% (95% CI, -6.1-9.1). Results of the NICE trial have been reported previously. Post-operative reassessment of ER expression changed the assessment of ER status...

SDF-1/CXCR4 expression in bladder cancer tissue and the correlation with negative costimulatory molecule PD-L1, cell apoptosis and invasion

Directory of Open Access Journals (Sweden)

Ming-Bao Ye

2017-06-01

Full Text Available Objective: To study the SDF-1/CXCR4 expression in bladder cancer tissue and the correlation with negative costimulatory molecule PD-L1, cell apoptosis and invasion. Methods: A total of 118 cases of bladder cancer tissue and para-carcinoma tissue surgically removed in our hospital between May 2014 and May 2016 were selected as the research samples, the RNA was extracted and then reverse-transcribed into cDNA, and the expression levels of SDF-1/ CXCR4, PD-L1/PD-1, cell apoptosis-related molecules and cell invasion-related molecules were detected. Results: SDF-1 and CXCR4 mRNA expression in bladder cancer tissue were significantly higher than those in para-carcinoma tissue; PD-L1, PD-1, Rec1, Survivin, MRPS5, Nanog, BCAPP2Ac, TRPM8, TRPV2, ILK, β-catenin and GUGBP1 mRNA expression in bladder cancer tissue were significantly higher than those in para-carcinoma tissue and positively correlated with SDF-1 and CXCR4 mRNA expression. Conclusion: Highly expressed SDF-1/CXCR4 in bladder cancer tissue are closely related to the high expression of negative costimulatory molecule PD-L1, pro-proliferation molecules and proinvasion molecules, and SDF-1/CXCR4 can promote the immune escape, proliferation and invasion of bladder cancer cells.

Microbial trophic interactions and mcrA gene expression in monitoring of anaerobic digesters

Science.gov (United States)

Alvarado, Alejandra; Montañez-Hernández, Lilia E.; Palacio-Molina, Sandra L.; Oropeza-Navarro, Ricardo; Luévanos-Escareño, Miriam P.; Balagurusamy, Nagamani

2014-01-01

Anaerobic digestion (AD) is a biological process where different trophic groups of microorganisms break down biodegradable organic materials in the absence of oxygen. A wide range of AD technologies is being used to convert livestock manure, municipal and industrial wastewaters, and solid organic wastes into biogas. AD gains importance not only because of its relevance in waste treatment but also because of the recovery of carbon in the form of methane, which is a renewable energy and is used to generate electricity and heat. Despite the advances on the engineering and design of new bioreactors for AD, the microbiology component always poses challenges. Microbiology of AD processes is complicated as the efficiency of the process depends on the interactions of various trophic groups involved. Due to the complex interdependence of microbial activities for the functionality of the anaerobic bioreactors, the genetic expression of mcrA, which encodes a key enzyme in methane formation, is proposed as a parameter to monitor the process performance in real time. This review evaluates the current knowledge on microbial groups, their interactions, and their relationship to the performance of anaerobic biodigesters with a focus on using mcrA gene expression as a tool to monitor the process. PMID:25429286

Microbial trophic interactions and mcrA gene expression in monitoring of anaerobic digesters

Directory of Open Access Journals (Sweden)

Alejandra eAlvarado

2014-11-01

Full Text Available Anaerobic digestion (AD is a biological process where different trophic groups of microorganisms break down biodegradable organic materials in the absence of oxygen. A wide range of anaerobic digestion technologies is being used to convert livestock manure, municipal and industrial wastewaters, and solid organic wastes into biogas. AD gains importance not only because of its relevance in waste treatment but also because of the recovery of carbon in the form of methane, which is a renewable energy and is used to generate electricity and heat. Despite the advances on the engineering and design of new bioreactors for anaerobic digestion, the microbiology component always poses challenges. Microbiology of AD processes is complicated as the efficiency of the process depends on the interactions of various trophic groups involved. Due to the complex interdependence of microbial activities for the functionality of the anaerobic bioreactors, the genetic expression of mcrA, which encodes a key enzyme in methane formation, is proposed as a parameter to monitor the process performance in real time. This review evaluates the current knowledge on microbial groups, their interactions and their relationship to the performance of anaerobic biodigesters with a focus on using mcrA gene expression as a tool to monitor the process.

Use of Wilms Tumor 1 Gene Expression as a Reliable Marker for Prognosis and Minimal Residual Disease Monitoring in Acute Myeloid Leukemia With Normal Karyotype Patients.

Science.gov (United States)

Marjanovic, Irena; Karan-Djurasevic, Teodora; Ugrin, Milena; Virijevic, Marijana; Vidovic, Ana; Tomin, Dragica; Suvajdzic Vukovic, Nada; Pavlovic, Sonja; Tosic, Natasa

2017-05-01

Acute myeloid leukemia with normal karyotype (AML-NK) represents the largest group of AML patients classified with an intermediate prognosis. A constant need exists to introduce new molecular markers for more precise risk stratification and for minimal residual disease (MRD) monitoring. Quantitative assessment of Wilms tumor 1 (WT1) gene transcripts was performed using real-time polymerase chain reaction. The bone marrow samples were collected at the diagnosis from 104 AML-NK patients and from 34 of these patients during follow-up or disease relapse. We found that overexpression of the WT1 gene (WT1 high status), present in 25.5% of patients, was an independent unfavorable factor for achieving complete remission. WT1 high status was also associated with resistance to therapy and shorter disease-free survival and overall survival. Assessment of the log reduction value of WT1 expression, measured in paired diagnosis/complete remission samples, revealed that patients with a log reduction of < 2 had a tendency toward shorter disease-free survival and overall survival and a greater incidence of disease relapse. Combining WT1 gene expression status with NPM1 and FLT3-ITD mutational status, we found that the tumor behavior of intermediate patients (FLT3-ITD - /NPM1 - double negative) with WT1 high status is almost the same as the tumor behavior of the adverse risk group. WT1 expression status represents a good molecular marker of prognosis, response to treatment, and MRD monitoring. Above all, the usage of the WT1 expression level as an additional marker for more precise risk stratification of AML-NK patients could lead to more adapted, personalized treatment protocols. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessment of Learners' Attention to E-Learning by Monitoring Facial Expressions for Computer Network Courses

Science.gov (United States)

Chen, Hong-Ren

2012-01-01

Recognition of students' facial expressions can be used to understand their level of attention. In a traditional classroom setting, teachers guide the classes and continuously monitor and engage the students to evaluate their understanding and progress. Given the current popularity of e-learning environments, it has become important to assess the…

Tenebrio molitor Gram-negative-binding protein 3 (TmGNBP3) is essential for inducing downstream antifungal Tenecin 1 gene expression against infection with Beauveria bassiana JEF-007.

Science.gov (United States)

Yang, Yi-Ting; Lee, Mi Rong; Lee, Se Jin; Kim, Sihyeon; Nai, Yu-Shin; Kim, Jae Su

2017-05-23

The Toll signaling pathway is responsible for defense against both Gram-positive bacteria and fungi. Gram-negative binding protein 3 (GNBP3) has a strong affinity for the fungal cell wall component, β-1,3-glucan, which can activate the prophenoloxidase (proPO) cascade and induce the Toll signaling pathway. Myeloid differentiation factor 88 (MyD88) is an intracellular adaptor protein involved in the Toll signaling pathway. In this study, we monitored the response of 5 key genes (TmGNBP3, TmMyD88, and Tenecin 1, 2, and 3) in the Toll pathway of the mealworm Tenebrio molitor immune system against the fungus Beauveria bassiana JEF-007 using RT-PCR. TmGNBP3, Tenecin 1, and Tenecin 2 were significantly upregulated after fungal infection. To better understand the roles of the Toll signaling pathway in the mealworm immune system, TmGNBP3 and TmMyD88 were knocked down by RNAi silencing. Target gene expression levels decreased at 2 d postknockdown and were dramatically reduced at 6 d post-dsRNA injection. Therefore, mealworms were compromised by B. bassiana JEF-007 at 6 d post-dsRNA injection. Silencing of TmMyD88 and TmGNBP3 resulted in reduced resistance of the host to fungal infection. Particularly, reducing TmGNBP3 levels obviously downregulated Tenecin 1 and Tenecin 2 expression levels, whereas silencing TmMyD88 expression resulted in decreased Tenecin 2 expression. These results indicate that TmGNBP3 is essential to induce downstream antifungal peptide Tenecin 1 expression against B. bassiana JEF-007. © 2017 Institute of Zoology, Chinese Academy of Sciences.

Transforming growth factor β-activated kinase 1 negatively regulates interleukin-1α-induced stromal-derived factor-1 expression in vascular smooth muscle cells

Energy Technology Data Exchange (ETDEWEB)

Yang, Bin [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Li, Wei [Department of Gerontology, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Zheng, Qichang [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Qin, Tao [Department of Hepatobiliary Pancreatic Surgery, People' s Hospital of Zhengzhou University, School of Medicine, Zhengzhou University, Zhengzhou 450003 (China); Wang, Kun; Li, Jinjin; Guo, Bing; Yu, Qihong; Wu, Yuzhe; Gao, Yang; Cheng, Xiang; Hu, Shaobo; Kumar, Stanley Naveen [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China); Liu, Sanguang, E-mail: sanguang1998@sina.com [Department of Hepatobiliary Surgery, The Second Hospital, Hebei Medical University, Shijiazhuang 050000 (China); Song, Zifang, E-mail: zsong@hust.edu.cn [Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huangzhong University of Science and Technology, Wuhan 430022 (China)

2015-07-17

Stromal-derived Factor-1 (SDF-1) derived from vascular smooth muscle cells (VSMCs) contributes to vascular repair and remodeling in various vascular diseases. In this study, the mechanism underlying regulation of SDF-1 expression by interleukin-1α (IL-1α) was investigated in primary rat VSMCs. We found IL-1α promotes SDF-1 expression by up-regulating CCAAT-enhancer-binding protein β (C/EBPβ) in an IκB kinase β (IKKβ) signaling-dependent manner. Moreover, IL-1α-induced expression of C/EBPβ and SDF-1 was significantly potentiated by knockdown of transforming growth factor β-activated kinase 1 (TAK1), an upstream activator of IKKβ signaling. In addition, we also demonstrated that TAK1/p38 mitogen-activated protein kinase (p38 MAPK) signaling exerted negative effect on IL-1α-induced expression of C/EBPβ and SDF-1 through counteracting ROS-dependent up-regulation of nuclear factor erythroid 2-related factor 2 (NRF2). In conclusion, TAK1 acts as an important regulator of IL-1α-induced SDF-1 expression in VSMCs, and modulating activity of TAK1 may serve as a potential strategy for modulating vascular repair and remodeling. - Highlights: • IL-1α induces IKKβ signaling-dependent SDF-1 expression by up-regulating C/EBPβ. • Activation of TAK1 by IL-1α negatively regulates C/EBPβ-dependent SDF-1 expression. • IL-1α-induced TAK1/p38 MAPK signaling counteracts ROS-dependent SDF-1 expression. • TAK1 counteracts IL-1α-induced SDF-1 expression by attenuating NRF2 up-regulation.

Transforming growth factor β-activated kinase 1 negatively regulates interleukin-1α-induced stromal-derived factor-1 expression in vascular smooth muscle cells

International Nuclear Information System (INIS)

Yang, Bin; Li, Wei; Zheng, Qichang; Qin, Tao; Wang, Kun; Li, Jinjin; Guo, Bing; Yu, Qihong; Wu, Yuzhe; Gao, Yang; Cheng, Xiang; Hu, Shaobo; Kumar, Stanley Naveen; Liu, Sanguang; Song, Zifang

2015-01-01

Stromal-derived Factor-1 (SDF-1) derived from vascular smooth muscle cells (VSMCs) contributes to vascular repair and remodeling in various vascular diseases. In this study, the mechanism underlying regulation of SDF-1 expression by interleukin-1α (IL-1α) was investigated in primary rat VSMCs. We found IL-1α promotes SDF-1 expression by up-regulating CCAAT-enhancer-binding protein β (C/EBPβ) in an IκB kinase β (IKKβ) signaling-dependent manner. Moreover, IL-1α-induced expression of C/EBPβ and SDF-1 was significantly potentiated by knockdown of transforming growth factor β-activated kinase 1 (TAK1), an upstream activator of IKKβ signaling. In addition, we also demonstrated that TAK1/p38 mitogen-activated protein kinase (p38 MAPK) signaling exerted negative effect on IL-1α-induced expression of C/EBPβ and SDF-1 through counteracting ROS-dependent up-regulation of nuclear factor erythroid 2-related factor 2 (NRF2). In conclusion, TAK1 acts as an important regulator of IL-1α-induced SDF-1 expression in VSMCs, and modulating activity of TAK1 may serve as a potential strategy for modulating vascular repair and remodeling. - Highlights: • IL-1α induces IKKβ signaling-dependent SDF-1 expression by up-regulating C/EBPβ. • Activation of TAK1 by IL-1α negatively regulates C/EBPβ-dependent SDF-1 expression. • IL-1α-induced TAK1/p38 MAPK signaling counteracts ROS-dependent SDF-1 expression. • TAK1 counteracts IL-1α-induced SDF-1 expression by attenuating NRF2 up-regulation

Salivary expression of soluble HER2 in breast cancer patients with positive and negative HER2 status

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Laidi F

2014-07-01

Full Text Available Fatna Laidi,1 Amal Bouziane,2 Amina Lakhdar,3 Samira Khabouze,3 Brahim Rhrab,3 Fatima Zaoui1 1Oral Biomechanics and Biotechnology Research Unit, Faculty of Dental Medicine, 2Department of Periodontology, Faculty of Dental Medicine, Biostatistical, Clinical and Epidemiological Research Laboratory, Faculty of Medicine and Pharmacy, 3Department of Obstetrics and Gynecology, Ibn Sina University Hospital, Rabat, Morocco Background: The aim of this study was to investigate the relationship between salivary concentration of the soluble fragment of the HER2 (human epidermal growth factor receptor protein and its status in mammary tissues. Methods: This case-control study was done in 27 breast cancer patients with no visible metastatic disease treated at the gynecology service, Maternity Souissi Hospital, Rabat, Morocco. Two groups were selected, ie, patients with positive and negative HER2 status in mammary tissue. The salivary HER2 protein concentration was assessed by enzyme-linked immunosorbent assay. The salivary HER2 concentration was compared between the HER2-positive and HER2-negative groups using the Mann-Whitney U test. A P-value <0.05 was considered to be statistically significant. Results: No statistically significant difference in salivary HER2 protein expression was found between the case and control groups. There was also no significant difference in clinical characteristics according to positive and negative HER2 status (P>0.05, except for the progesterone hormone receptor which was statistically significant in both the case and control groups (P=0.047. Conclusion: According to our data, salivary expression of the HER2 receptor may not be a reliable alternative to tissue assessment. Keywords: breast cancer, HER2, saliva, diagnosis

Human Colon Tumors Express a Dominant-Negative Form of SIGIRR That Promotes Inflammation and Colitis-Associated Colon Cancer in Mice.

Science.gov (United States)

Zhao, Junjie; Bulek, Katarzyna; Gulen, Muhammet F; Zepp, Jarod A; Karagkounis, Georgio; Martin, Bradley N; Zhou, Hao; Yu, Minjia; Liu, Xiuli; Huang, Emina; Fox, Paul L; Kalady, Matthew F; Markowitz, Sanford D; Li, Xiaoxia

2015-12-01

Single immunoglobulin and toll-interleukin 1 receptor (SIGIRR), a negative regulator of the Toll-like and interleukin-1 receptor (IL-1R) signaling pathways, controls intestinal inflammation and suppresses colon tumorigenesis in mice. However, the importance of SIGIRR in human colorectal cancer development has not been determined. We investigated the role of SIGIRR in development of human colorectal cancer. We performed RNA sequence analyses of pairs of colon tumor and nontumor tissues, each collected from 68 patients. Immunoblot and immunofluorescence analyses were used to determine levels of SIGIRR protein in primary human colonic epithelial cells, tumor tissues, and colon cancer cell lines. We expressed SIGIRR and mutant forms of the protein in Vaco cell lines. We created and analyzed mice that expressed full-length (control) or a mutant form of Sigirr (encoding SIGIRR(N86/102S), which is not glycosylated) specifically in the intestinal epithelium. Some mice were given azoxymethane (AOM) and dextran sulfate sodium to induce colitis-associated cancer. Intestinal tissues were collected and analyzed by immunohistochemical and gene expression profile analyses. RNA sequence analyses revealed increased expression of a SIGIRR mRNA isoform, SIGIRR(ΔE8), in colorectal cancer tissues compared to paired nontumor tissues. SIGIRR(ΔE8) is not modified by complex glycans and is therefore retained in the cytoplasm-it cannot localize to the cell membrane or reduce IL1R signaling. SIGIRR(ΔE8) interacts with and has a dominant-negative effect on SIGIRR, reducing its glycosylation, localization to the cell surface, and function. Most SIGIRR detected in human colon cancer tissues was cytoplasmic, whereas in nontumor tissues it was found at the cell membrane. Mice that expressed SIGIRR(N86/102S) developed more inflammation and formed larger tumors after administration of azoxymethane and dextran sulfate sodium than control mice; colon tissues from these mutant mice expressed

Cosmic Rays and Clouds, 1. Formation of Lead Mesoatoms In Neutron Monitor By Soft Negative Muons and Expected Atmospheric Electric Field Effect In The Cosmic Ray Neutron Component

Science.gov (United States)

Dorman, L. I.; Dorman, I. V.

We extend our model (Dorman and Dorman, 1995) of cosmic ray atmospheric electric field effect on the case of neutron monitor. We take into account that about 0.07 of neu- tron monitor counting rate caused by negative soft muons captured by lead nucleons and formed mesoatoms with generation of several MeV energy neutrons from lead. In this case the neutron monitor or neutron supermonitor works as analyzer which de- tects muons of only one, negative sign. It is very important because the atmospheric electric field effect have opposite signs for positive and negative muons that main part of this effect in the muon telescope or in ionization chamber is compensated and we can observe only small part of total effect of one sign muons. On the basis of our gen- eral theory of cosmic ray meteorological effects with taking into account of negative soft muon acceleration and deceleration in the Earth atmosphere (in dependence of di- rection and intensity of electric field) we discuss the possibility of existing this effect in cosmic ray neutron component and made some rough estimations. REFERENCES: Dorman L.I. and Dorman I.V., 1995. "Cosmic-ray atmospheric electric field effects". Canadian J. of Physics, Vol. 73, pp. 440-443.

Plasmid Negative Regulation of CPAF Expression Is Pgp4 Independent and Restricted to Invasive Chlamydia trachomatis Biovars

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Michael John Patton

2018-01-01

Full Text Available Chlamydia trachomatis is an obligate intracellular bacterial pathogen that causes blinding trachoma and sexually transmitted disease. C. trachomatis isolates are classified into 2 biovars—lymphogranuloma venereum (LGV and trachoma—which are distinguished biologically by their natural host cell infection tropism. LGV biovars infect macrophages and are invasive, whereas trachoma biovars infect oculo-urogenital epithelial cells and are noninvasive. The C. trachomatis plasmid is an important virulence factor in the pathogenesis of these infections. Central to its pathogenic role is the transcriptional regulatory function of the plasmid protein Pgp4, which regulates the expression of plasmid and chromosomal virulence genes. As many gene regulatory functions are post-transcriptional, we employed a comparative proteomic study of cells infected with plasmid-cured C. trachomatis serovars A and D (trachoma biovar, a L2 serovar (LGV biovar, and the L2 serovar transformed with a plasmid containing a nonsense mutation in pgp4 to more completely elucidate the effects of the plasmid on chlamydial infection biology. Our results show that the Pgp4-dependent elevations in the levels of Pgp3 and a conserved core set of chromosomally encoded proteins are remarkably similar for serovars within both C. trachomatis biovars. Conversely, we found a plasmid-dependent, Pgp4-independent, negative regulation in the expression of the chlamydial protease-like activity factor (CPAF for the L2 serovar but not the A and D serovars. The molecular mechanism of plasmid-dependent negative regulation of CPAF expression in the LGV serovar is not understood but is likely important to understanding its macrophage infection tropism and invasive infection nature.

Triple negative breast cancers have a reduced expression of DNA repair genes.

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Enilze Ribeiro

Full Text Available DNA repair is a key determinant in the cellular response to therapy and tumor repair status could play an important role in tailoring patient therapy. Our goal was to evaluate the mRNA of 13 genes involved in different DNA repair pathways (base excision, nucleotide excision, homologous recombination, and Fanconi anemia in paraffin embedded samples of triple negative breast cancer (TNBC compared to luminal A breast cancer (LABC. Most of the genes involved in nucleotide excision repair and Fanconi Anemia pathways, and CHK1 gene were significantly less expressed in TNBC than in LABC. PARP1 levels were higher in TNBC than in LABC. In univariate analysis high level of FANCA correlated with an increased overall survival and event free survival in TNBC; however multivariate analyses using Cox regression did not confirm FANCA as independent prognostic factor. These data support the evidence that TNBCs compared to LABCs harbour DNA repair defects.

Timing matters: negative emotion elicited 5 min but not 30 min or 45 min after learning enhances consolidation of internal-monitoring source memory.

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Wang, Bo; Bukuan, Sun

2015-05-01

Two experiments examined the time-dependent effects of negative emotion on consolidation of item and internal-monitoring source memory. In Experiment 1, participants (n=121) learned a list of words. They were asked to read aloud half of the words and to think about the remaining half. They were instructed to memorize each word and its associative cognitive operation ("reading" versus "thinking"). Immediately following learning they conducted free recall and then watched a 3-min either neutral or negative video clip when 5 min, 30 min or 45 min had elapsed after learning. Twenty-four hours later they returned to take surprise tests for item and source memory. Experiment 2 was similar to Experiment 1 except that participants, without conducting an immediate test of free recall, took tests of source memory for all encoded words both immediately and 24 h after learning. Experiment 1 showed that negative emotion enhanced consolidation of item memory (as measured by retention ratio of free recall) regardless of delay of emotion elicitation and that negative emotion enhanced consolidation of source memory when it was elicited at a 5 min delay but reduced consolidation of source memory when it was elicited at a 30 min delay; when elicited at a 45 min delay, negative emotion had little effect. Furthermore, Experiment 2 replicated the enhancement effect on source memory in the 5 min delay even when participants were tested on all the encoded words. The current study partially replicated prior studies on item memory and extends the literature by providing evidence for a time-dependent effect of negative emotion on consolidation of source memory based on internal monitoring. Copyright © 2015 Elsevier B.V. All rights reserved.

Pyruvate dehydrogenase expression is negatively associated with cell stemness and worse clinical outcome in prostate cancers

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Zhong, Yali; Li, Xiaoli; Ji, Yasai; Li, Xiaoran; Li, Yaqing; Yu, Dandan; Yuan, Yuan; Liu, Jian; Li, Huixiang; Zhang, Mingzhi; Ji, Zhenyu; Fan, Dandan; Wen, Jianguo; Goscinski, Mariusz Adam; Yuan, Long; Hao, Bin; Nesland, Jahn M; Suo, Zhenhe

2017-01-01

Cells generate adenosine-5′-triphosphate (ATP), the major currency for energy-consuming reactions, through mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis. One of the remarkable features of cancer cells is aerobic glycolysis, also known as the “Warburg Effect”, in which cancer cells rely preferentially on glycolysis instead of mitochondrial OXPHOS as the main energy source even in the presence of high oxygen tension. One of the main players in controlling OXPHOS is the mitochondrial gatekeeperpyruvate dehydrogenase complex (PDHc) and its major subunit is E1α (PDHA1). To further analyze the function of PDHA1 in cancer cells, it was knock out (KO) in the human prostate cancer cell line LnCap and a stable KO cell line was established. We demonstrated that PDHA1 gene KO significantly decreased mitochondrial OXPHOS and promoted anaerobic glycolysis, accompanied with higher stemness phenotype including resistance to chemotherapy, enhanced migration ability and increased expression of cancer stem cell markers. We also examined PDHA1 protein expression in prostate cancer tissues by immunohistochemistry and observed that reduced PDHA1 protein expression in clinical prostate carcinomas was significantly correlated with poor prognosis. Collectively, our results show that negative PDHA1 gene expressionis associated with significantly higher cell stemness in prostate cancer cells and reduced protein expression of this gene is associated with shorter clinical outcome in prostate cancers. PMID:28076853

High Stromal Carbonic Anhydrase IX Expression Is Associated With Decreased Survival in p16-Negative Head-and-Neck Tumors

International Nuclear Information System (INIS)

Brockton, Nigel; Dort, Joseph; Lau, Harold; Hao, Desiree; Brar, Sony; Klimowicz, Alexander; Petrillo, Stephanie; Diaz, Roman; Doll, Corinne; Magliocco, Anthony

2011-01-01

Purpose: Head-and-neck squamous cell carcinoma (HNSCC) is the fifth most common malignancy worldwide. Alcohol use and tobacco use are the most established risk factors; however, human papilloma virus (HPV) infection is a major risk factor for a subset of HNSCCs. Although HPV-positive tumors typically present at a more advanced stage at diagnosis, they are associated with a better prognosis. Tumor hypoxia confers poor prognosis and treatment failure, but direct tumor oxygen measurement is challenging. Endogenous markers of hypoxia (EMHs) have been proposed but have not replicated the prognostic utility of direct oxygen measurement. The expression of endogenous markers of hypoxia may be influenced by oxygen-independent factors, such as the HPV status of the tumor. Methods and Materials: Consecutive cases of locally advanced HNSCC, treated with a uniform regimen of combined radiotherapy and chemotherapy, were identified. Tissue microarrays were assembled from triplicate 0.6-mm cores of archived tumor tissue. HPV status was inferred from semiquantitative p16 immunostaining and directly measured by use of HPV-specific chromogenic in situ hybridization and polymerase chain reaction. Automated quantitative fluorescent immunohistochemistry was conducted to measure epithelial and stromal expression of carbonic anhydrase IX (CAIX) and glucose transporter 1 (GLUT1). Results: High stromal CAIX expression was associated with significantly reduced overall survival (p = 0.03) in patients with p16-negative tumors. Conclusions: This is the first study to use quantitative immunohistochemistry to examine endogenous markers of hypoxia stratified by tumor p16/HPV status. Assessment of CAIX expression in p16-negative HNSCC could identify patients with the least favorable prognosis and inform therapeutic strategies.

The FasX Small Regulatory RNA Negatively Regulates the Expression of Two Fibronectin-Binding Proteins in Group A Streptococcus.

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Danger, Jessica L; Makthal, Nishanth; Kumaraswami, Muthiah; Sumby, Paul

2015-12-01

The group A Streptococcus (GAS; Streptococcus pyogenes) causes more than 700 million human infections each year. The success of this pathogen can be traced in part to the extensive arsenal of virulence factors that are available for expression in temporally and spatially specific manners. To modify the expression of these virulence factors, GAS use both protein- and RNA-based regulators, with the best-characterized RNA-based regulator being the small regulatory RNA (sRNA) FasX. FasX is a 205-nucleotide sRNA that contributes to GAS virulence by enhancing the expression of the thrombolytic secreted virulence factor streptokinase and by repressing the expression of the collagen-binding cell surface pili. Here, we have expanded the FasX regulon, showing that this sRNA also negatively regulates the expression of the adhesion- and internalization-promoting, fibronectin-binding proteins PrtF1 and PrtF2. FasX posttranscriptionally regulates the expression of PrtF1/2 through a mechanism that involves base pairing to the prtF1 and prtF2 mRNAs within their 5' untranslated regions, overlapping the mRNA ribosome-binding sites. Thus, duplex formation between FasX and the prtF1 and prtF2 mRNAs blocks ribosome access, leading to an inhibition of mRNA translation. Given that FasX positively regulates the expression of the spreading factor streptokinase and negatively regulates the expression of the collagen-binding pili and of the fibronectin-binding PrtF1/2, our data are consistent with FasX functioning as a molecular switch that governs the transition of GAS between the colonization and dissemination stages of infection. More than half a million deaths each year are a consequence of infections caused by GAS. Insights into how this pathogen regulates the production of proteins during infection may facilitate the development of novel therapeutic or preventative regimens aimed at inhibiting this activity. Here, we have expanded insight into the regulatory activity of the GAS small

The prognostic value of oncogenic antigen 519 (OA-519) expression and proliferative activity detected by antibody MIB-1 in node-negative breast cancer

DEFF Research Database (Denmark)

Jensen, V; Ladekarl, M; Holm-Nielsen, P

1995-01-01

The prognostic value of oncogenic antigen 519 (OA-519) expression and tumour proliferative activity was evaluated in a retrospective series of 118 patients with low-risk breast cancer. Low risk was defined as negative axillary nodes, tumour diameter histological evidence...... analysis, both the MIB-1 index and OA-519 expression were of independent prognostic value (2p breast cancer who might benefit from adjuvant therapy....

Negative Symptom Dimensions of the Positive and Negative Syndrome Scale Across Geographical Regions: Implications for Social, Linguistic, and Cultural Consistency.

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Khan, Anzalee; Liharska, Lora; Harvey, Philip D; Atkins, Alexandra; Ulshen, Daniel; Keefe, Richard S E

2017-12-01

Objective: Recognizing the discrete dimensions that underlie negative symptoms in schizophrenia and how these dimensions are understood across localities might result in better understanding and treatment of these symptoms. To this end, the objectives of this study were to 1) identify the Positive and Negative Syndrome Scale negative symptom dimensions of expressive deficits and experiential deficits and 2) analyze performance on these dimensions over 15 geographical regions to determine whether the items defining them manifest similar reliability across these regions. Design: Data were obtained for the baseline Positive and Negative Syndrome Scale visits of 6,889 subjects across 15 geographical regions. Using confirmatory factor analysis, we examined whether a two-factor negative symptom structure that is found in schizophrenia (experiential deficits and expressive deficits) would be replicated in our sample, and using differential item functioning, we tested the degree to which specific items from each negative symptom subfactor performed across geographical regions in comparison with the United States. Results: The two-factor negative symptom solution was replicated in this sample. Most geographical regions showed moderate-to-large differential item functioning for Positive and Negative Syndrome Scale expressive deficit items, especially N3 Poor Rapport, as compared with Positive and Negative Syndrome Scale experiential deficit items, showing that these items might be interpreted or scored differently in different regions. Across countries, except for India, the differential item functioning values did not favor raters in the United States. Conclusion: These results suggest that the Positive and Negative Syndrome Scale negative symptom factor can be better represented by a two-factor model than by a single-factor model. Additionally, the results show significant differences in responses to items representing the Positive and Negative Syndrome Scale expressive

All in Its Proper Time: Monitoring the Emergence of a Memory Bias for Novel, Arousing-Negative Words in Individuals with High and Low Trait Anxiety

OpenAIRE

Eden, Annuschka Salima; Zwitserlood, Pienie; Keuper, Katharina; Junghöfer, Markus; Laeger, Inga; Zwanzger, Peter; Dobel, Christian

2014-01-01

The well-established memory bias for arousing-negative stimuli seems to be enhanced in high trait-anxious persons and persons suffering from anxiety disorders. We monitored the emergence and development of such a bias during and after learning, in high and low trait anxious participants. A word-learning paradigm was applied, consisting of spoken pseudowords paired either with arousing-negative or neutral pictures. Learning performance during training evidenced a short-lived advantage for arou...

Electric Sensors for Express-Method Checking of Liquid Quality Level Monitoring

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Petro STOLYARCHUK

2010-02-01

Full Text Available The research covered in the suggested article is meant for ecological monitoring in the broad sense. The express-method of water solution quality level estimation and the technique of fast response to the quality level of industrial, agricultural and domestic wastewaters along with food products are proposed. The novelty of the proposed technique roots in the implementation of suggested methods and means of electric parameter measurement aimed at the quality index controlling of nonelectric qualimetry objects. Relevant research includes the exploration of water-solutions as well as different-level purification of industrial and domestic spillage waters, colloid solutions (cream, milk with the known contaminants, mixtures of superficially active substances and chlorine-containing substances.

Negative regulation of retrovirus expression in embryonal carcinoma cells mediated by an intragenic domain.

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Loh, T P; Sievert, L L; Scott, R W

1988-11-01

An intragenic region spanning the tRNA primer binding site of a Moloney murine leukemia virus recombinant retrovirus was found to restrict expression specifically in embryonal carcinoma (EC) cells. When the inhibitory domain was present, the levels of steady-state RNA synthesized from integrated recombinant templates in stable cotransformation assays were reduced 20-fold in EC cells but not in C2 myoblast cells. Transient-cotransfection assays showed that repression of a template containing the EC-specific inhibitory component was relieved by an excess of specific competitor DNA. In addition, repression mediated by the inhibitory component was orientation independent. This evidence demonstrates the presence of a saturable, trans-acting negative regulatory factor(s) in EC cells and suggests that the interaction of the factor(s) with the intragenic inhibitory component occurs at the DNA level.

Co-receptor choice by V alpha14i NKT cells is driven by Th-POK expression rather than avoidance of CD8-mediated negative selection.

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Engel, Isaac; Hammond, Kirsten; Sullivan, Barbara A; He, Xi; Taniuchi, Ichiro; Kappes, Dietmar; Kronenberg, Mitchell

2010-05-10

Mouse natural killer T (NKT) cells with an invariant V alpha14-J alpha18 rearrangement (V alpha14 invariant [V alpha14i] NKT cells) are either CD4(+)CD8(-) or CD4(-)CD8(-). Because transgenic mice with forced CD8 expression in all T cells exhibited a profound NKT cell deficit, the absence of CD8 has been attributed to negative selection. We now present evidence that CD8 does not serve as a coreceptor for CD1d recognition and that the defect in development in CD8 transgene homozygous mice is the result of a reduction in secondary T cell receptor alpha rearrangements. Thymocytes from mice hemizygous for the CD8 transgene have a less severe rearrangement defect and have functional CD8(+) V alpha14i NKT cells. Furthermore, we demonstrate that the transcription factor Th, Poxviruses and Zinc finger, and Krüppel family (Th-POK) is expressed by V alpha14i NKT cells throughout their differentiation and is necessary both to silence CD8 expression and for the functional maturity of V alpha14i NKT cells. We therefore suggest that Th-POK expression is required for the normal development of V alpha14i NKT cells and that the absence of CD8 expression by these cells is a by-product of such expression, as opposed to the result of negative selection of CD8-expressing V alpha14i NKT cells.

The clinicopathologic characteristics and prognostic significance of triple-negativity in node-negative breast cancer

International Nuclear Information System (INIS)

Rhee, Jiyoung; Kim, Tae-You; Han, Sae-Won; Oh, Do-Youn; Kim, Jee Hyun; Im, Seock-Ah; Han, Wonshik; Ae Park, In; Noh, Dong-Young; Bang, Yung-Jue

2008-01-01

Triple-negative (TN) breast cancer, which is defined as being negative for the estrogen receptor (ER), the progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER-2), represents a subset of breast cancer with different biologic behaviour. We investigated the clinicopathologic characteristics and prognostic indicators of lymph node-negative TN breast cancer. Medical records were reviewed from patients with node-negative breast cancer who underwent curative surgery at Seoul National University Hospital between Jan. 2000 and Jun. 2003. Clinicopathologic variables and clinical outcomes were evaluated. Among 683 patients included, 136 had TN breast cancer and 529 had non-TN breast cancer. TN breast cancer correlated with younger age (< 35 y, p = 0.003), and higher histologic and nuclear grade (p < 0.001). It also correlated with a molecular profile associated with biological aggressiveness: negative for bcl-2 expression (p < 0.001), positive for the epidermal growth factor receptor (p = 0.003), and a high level of p53 (p < 0.001) and Ki67 expression (p < 0.00). The relapse rates during the follow-up period (median, 56.8 months) were 14.7% for TN breast cancer and 6.6% for non-TN breast cancer (p = 0.004). Relapse free survival (RFS) was significantly shorter among patients with TN breast cancer compared with those with non-TN breast cancer (4-year RFS rate 85.5% vs. 94.2%, respectively; p = 0.001). On multivariate analysis, young age, close resection margin, and triple-negativity were independent predictors of shorter RFS. TN breast cancer had higher relapse rate and more aggressive clinicopathologic characteristics than non-TN in node-negative breast cancer. Thus, TN breast cancer should be integrated into the risk factor analysis for node-negative breast cancer

Monitoring the effects of toxic chemicals on protein expression

International Nuclear Information System (INIS)

Giometti, C.S.; Taylor, J.

1987-01-01

Two-dimensional gel electrophoresis coupled with computer-assisted image and data analysis was used to monitor protein populations for both qualitative and quantitative changes induced by exposure to chemicals. For mutagenesis studies designed to screen for heritable mutations, a computer-assisted search of the optical density data from 2DE patterns was used to look for (a) new protein spots, (b) missing protein spots and/or (c) altered expression of normal protein spots. Using this approach, 320 mice were screened for mutations induced by treatment of sires with 150 mg/kg body weight of ethylnitrosourea (ENU) and four different mutations were identified. Protein patterns from 105 offspring from untreated male mice (controls) and 369 offspring from irradiated male mice (3 Gy gamma) were also screened. No heritable mutations were found in those data sets, however. In addition, protein changes were observed in livers of animals exposed to the hepatocellular peroxisomal proliferation agents (and carcinogens) Wy-14,643 and DEHP. The de novo synthesis of a new protein by these agents was demonstrated and quantitated

Selective androgen receptor modulators (SARMs) negatively regulate triple-negative breast cancer growth and epithelial:mesenchymal stem cell signaling.

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Narayanan, Ramesh; Ahn, Sunjoo; Cheney, Misty D; Yepuru, Muralimohan; Miller, Duane D; Steiner, Mitchell S; Dalton, James T

2014-01-01

The androgen receptor (AR) is the most highly expressed steroid receptor in breast cancer with 75-95% of estrogen receptor (ER)-positive and 40-70% of ER-negative breast cancers expressing AR. Though historically breast cancers were treated with steroidal androgens, their use fell from favor because of their virilizing side effects and the emergence of tamoxifen. Nonsteroidal, tissue selective androgen receptor modulators (SARMs) may provide a novel targeted approach to exploit the therapeutic benefits of androgen therapy in breast cancer. Since MDA-MB-453 triple-negative breast cancer cells express mutated AR, PTEN, and p53, MDA-MB-231 triple-negative breast cancer cells stably expressing wildtype AR (MDA-MB-231-AR) were used to evaluate the in vitro and in vivo anti-proliferative effects of SARMs. Microarray analysis and epithelial:mesenchymal stem cell (MSC) co-culture signaling studies were performed to understand the mechanisms of action. Dihydrotestosterone and SARMs, but not bicalutamide, inhibited the proliferation of MDA-MB-231-AR. The SARMs reduced the MDA-MB-231-AR tumor growth and tumor weight by greater than 90%, compared to vehicle-treated tumors. SARM treatment inhibited the intratumoral expression of genes and pathways that promote breast cancer development through its actions on the AR. SARM treatment also inhibited the metastasis-promoting paracrine factors, IL6 and MMP13, and subsequent migration and invasion of epithelial:MSC co-cultures. 1. AR stimulation inhibits paracrine factors that are important for MSC interactions and breast cancer invasion and metastasis. 2. SARMs may provide promise as novel targeted therapies to treat AR-positive triple-negative breast cancer.

Selective androgen receptor modulators (SARMs negatively regulate triple-negative breast cancer growth and epithelial:mesenchymal stem cell signaling.

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Ramesh Narayanan

Full Text Available The androgen receptor (AR is the most highly expressed steroid receptor in breast cancer with 75-95% of estrogen receptor (ER-positive and 40-70% of ER-negative breast cancers expressing AR. Though historically breast cancers were treated with steroidal androgens, their use fell from favor because of their virilizing side effects and the emergence of tamoxifen. Nonsteroidal, tissue selective androgen receptor modulators (SARMs may provide a novel targeted approach to exploit the therapeutic benefits of androgen therapy in breast cancer.Since MDA-MB-453 triple-negative breast cancer cells express mutated AR, PTEN, and p53, MDA-MB-231 triple-negative breast cancer cells stably expressing wildtype AR (MDA-MB-231-AR were used to evaluate the in vitro and in vivo anti-proliferative effects of SARMs. Microarray analysis and epithelial:mesenchymal stem cell (MSC co-culture signaling studies were performed to understand the mechanisms of action.Dihydrotestosterone and SARMs, but not bicalutamide, inhibited the proliferation of MDA-MB-231-AR. The SARMs reduced the MDA-MB-231-AR tumor growth and tumor weight by greater than 90%, compared to vehicle-treated tumors. SARM treatment inhibited the intratumoral expression of genes and pathways that promote breast cancer development through its actions on the AR. SARM treatment also inhibited the metastasis-promoting paracrine factors, IL6 and MMP13, and subsequent migration and invasion of epithelial:MSC co-cultures.1. AR stimulation inhibits paracrine factors that are important for MSC interactions and breast cancer invasion and metastasis. 2. SARMs may provide promise as novel targeted therapies to treat AR-positive triple-negative breast cancer.

Monitoring of Biodistribution and Persistence of Conditionally Replicative Adenovirus in a Murine Model of Ovarian Cancer Using Capsid-Incorporated mCherry and Expression of Human Somatostatin Receptor Subtype 2 Gene

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Igor P. Dmitriev

2014-10-01

Full Text Available A significant limiting factor to the human clinical application of conditionally replicative adenovirus (CRAd-based virotherapy is the inability to noninvasively monitor these agents and their potential persistence. To address this issue, we proposed a novel imaging approach that combines transient expression of the human somatostatin receptor (SSTR subtype 2 reporter gene with genetic labeling of the viral capsid with mCherry fluorescent protein. To test this dual modality system, we constructed the Ad5/3Δ24pIXcherry/SSTR CRAd and validated its capacity to generate fluorescent and nuclear signals in vitro and following intratumoral injection. Analysis of 64Cu-CB-TE2A-Y3-TATE biodistribution in mice revealed reduced uptake in tumors injected with the imaging CRAd relative to the replication-incompetent, Ad-expressing SSTR2 but significantly greater uptake compared to the negative CRAd control. Optical imaging demonstrated relative correlation of fluorescent signal with virus replication as determined by viral genome quantification in tumors. Positron emission tomography/computed tomography studies demonstrated that we can visualize radioactive uptake in tumors injected with imaging CRAd and the trend for greater uptake by standardized uptake value analysis compared to control CRAd. In the aggregate, the plasticity of our dual imaging approach should provide the technical basis for monitoring CRAd biodistribution and persistence in preclinical studies while offering potential utility for a range of clinical applications.

Aldehyde dehydrogenase 1 (ALDH1) expression is an independent prognostic factor in triple negative breast cancer (TNBC).

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Ma, Fei; Li, Huihui; Li, Yiqun; Ding, Xiaoyan; Wang, Haijuan; Fan, Ying; Lin, Chen; Qian, Haili; Xu, Binghe

2017-04-01

Triple negative breast cancer (TNBC) is a subset of breast cancer that is highly aggressive and has a poor prognosis. Meanwhile, cancer stem cells (CSCs) are also characterized by a strong tumorigenic potential, which might be partly responsible for the aggressive behavior of TNBC. We previously showed that CSCs are enriched in TNBC cell lines and tissues. Further experiments in animal models revealed higher tumorigenicity of CSCs sorted from TNBC cell lines. In this study, we aimed to determine the clinical relationship between CSCs and TNBC by exploring the expression of aldehyde dehydrogenase 1 (ALDH1), which is a putative marker of breast CSCs, in TNBC tissues.ALDH1 levels in paraffin-embedded tumor tissues from 158 TNBC patients were evaluated by immunohistochemistry staining using an ALDH1A1 primary antibody. Staining evaluation was performed independently by two pathologists, and the expression level of ALDH1 was evaluated in terms of the percentage and intensity of positive cells. The association of immunohistochemistry staining of ALDH1 expression with clinical parameters was also analyzed.ALDH1 expression in tumor cells was observed in 88 out of 158 cases (55.7%). Analysis of clinicopathological parameters showed that the immunohistochemistry staining of ALDH1 was significantly correlated with tumor size (P = 0.02) and stage (P = 0.04). Survival analysis in patients with ALDH1 expression demonstrated shorter relapse-free survival (RFS) and overall survival (OS) times (P = 0.01; P = 0.001). Moreover, Cox multivariate analysis revealed that ALDH1 expression was an independent prognostic indicator of RFS and OS (P = 0.04; P = 0.04).Immunohistochemistry staining of ALDH1 in tumor cells is an independent prognostic indicator of RFS and OS in TNBC patients.

miRNA-135b Contributes to Triple Negative Breast Cancer Molecular Heterogeneity: Different Expression Profile in Basal-like Versus non-Basal-like Phenotypes.

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Uva, Paolo; Cossu-Rocca, Paolo; Loi, Federica; Pira, Giovanna; Murgia, Luciano; Orrù, Sandra; Floris, Matteo; Muroni, Maria Rosaria; Sanges, Francesca; Carru, Ciriaco; Angius, Andrea; De Miglio, Maria Rosaria

2018-01-01

The clinical and genetic heterogeneity of Triple Negative Breast Cancer (TNBC) and the lack of unambiguous molecular targets contribute to the inadequacy of current therapeutic options for these variants. MicroRNAs (miRNA) are a class of small highly conserved regulatory endogenous non-coding RNA, which can alter the expression of genes encoding proteins and may play a role in the dysregulation of cellular pathways. Our goal was to improve the knowledge of the molecular pathogenesis of TNBC subgroups analyzing the miRNA expression profile, and to identify new prognostic and predictive biomarkers. We conducted a human miRNome analysis by TaqMan Low Density Array comparing different TNBC subtypes, defined by immunohistochemical basal markers EGFR and CK5/6. RT-qPCR confirmed differential expression of microRNAs. To inspect the function of the selected targets we perform Gene Ontology and KEGG enrichment analysis. We identified a single miRNA signature given by miR-135b expression level, which was strictly related to TNBC with basal-like phenotype. miR-135b target analysis revealed a role in the TGF-beta, WNT and ERBB pathways. A significant positive correlation was identified between neoplastic proliferative index and miR-135b expression. These findings confirm the oncogenic roles of miR-135b in the pathogenesis of TNBC expressing basal markers. A potential negative prognostic role of miR-135b overexpression might be related to the positive correlation with high proliferative index. Our study implies potential clinical applications: miR-135b could be a potential therapeutic target in basal-like TNBCs.

Thyroid hormone negatively regulates CDX2 and SOAT2 mRNA expression via induction of miRNA-181d in hepatic cells

Energy Technology Data Exchange (ETDEWEB)

Yap, Chui Sun; Sinha, Rohit Anthony [Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical School, 8, College Road, Singapore 169857 (Singapore); Ota, Sho; Katsuki, Masahito [Department of Molecular Endocrinology, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai 980-8575 (Japan); Yen, Paul Michael, E-mail: paul.yen@duke-nus.edu.sg [Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical School, 8, College Road, Singapore 169857 (Singapore)

2013-11-01

Highlights: •Thyroid hormone induces miR-181d expression in human hepatic cells and mouse livers. •Thyroid hormone downregulates CDX2 and SOAT2 (or ACAT2) via miR-181d. •miR-181d reduces cholesterol output from human hepatic cells. -- Abstract: Thyroid hormones (THs) regulate transcription of many metabolic genes in the liver through its nuclear receptors (TRs). Although the molecular mechanisms for positive regulation of hepatic genes by TH are well understood, much less is known about TH-mediated negative regulation. Recently, several nuclear hormone receptors were shown to downregulate gene expression via miRNAs. To further examine the potential role of miRNAs in TH-mediated negative regulation, we used a miRNA microarray to identify miRNAs that were directly regulated by TH in a human hepatic cell line. In our screen, we discovered that miRNA-181d is a novel hepatic miRNA that was regulated by TH in hepatic cell culture and in vivo. Furthermore, we identified and characterized two novel TH-regulated target genes that were downstream of miR-181d signaling: caudal type homeobox 2 (CDX2) and sterol O-acyltransferase 2 (SOAT2 or ACAT2). CDX2, a known positive regulator of hepatocyte differentiation, was regulated by miR-181d and directly activated SOAT2 gene expression. Since SOAT2 is an enzyme that generates cholesteryl esters that are packaged into lipoproteins, our results suggest miR-181d plays a significant role in the negative regulation of key metabolic genes by TH in the liver.

Clinical Significance of CK19 Negative Breast Cancer

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Fujisue, Mamiko, E-mail: nishimura.reiki@cityhosp-kumamoto.jp; Nishimura, Reiki; Okumura, Yasuhiro [Department of Breast and Endocrine Surgery, Kumamoto City Hospital, 1-1-60 Kotoh, Kumamoto City, Kumamoto 862-8505 (Japan); Tashima, Rumiko [Department of Surgery, Kumamoto City Hospital, 1-1-60 Kotoh, Kumamoto City, Kumamoto 862-8505 (Japan); Nishiyama, Yasuyuki; Osako, Tomofumi [Department of Breast and Endocrine Surgery, Kumamoto City Hospital, 1-1-60 Kotoh, Kumamoto City, Kumamoto 862-8505 (Japan); Toyozumi, Yasuo; Arima, Nobuyuki [Department of Pathology, Kumamoto City Hospital, 1-1-60 Kotoh, Kumamoto City, Kumamoto 862-8505 (Japan)

2012-12-21

Analysis of sentinel lymph nodes (SLNs) by means of One-Step Nucleic Acid Amplification (OSNA) is gaining widespread use as a quick and accurate method. This assay detects the expression level of cytokeratin 19 (CK19) which is present in some but not all breast tumors. In this study, the clinical significance of negative CK19 was investigated in 219 cases of primary breast cancer. In 179 patients with clinically negative nodes, OSNA and imprint smear cytology of SLN were performed simultaneously. The OSNA revealed a node-positive rate of 24.6%. Negative CK19 correlated significantly with negative ER/PgR and higher Ki-67 values, and marginally with higher nuclear grade and p53 overexpression. The triple negative subtype showed lower CK19 expression. OSNA revealed that one of the negative CK19 cases was actually a false negative but this was corrected with the use of the imprint smear cytology. In conclusion, CK19 negativity reflected the aggressiveness of primary breast cancer. OSNA assay used to analyze SLN was useful, but there is a possibility that it will mistakenly detect false negatives in CK19 negative tumors. Therefore, in tumors with negative CK19, the imprint smear cytology may be more useful in cases with macrometastasis.

Clinical Significance of CK19 Negative Breast Cancer

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Nobuyuki Arima

2012-12-01

Full Text Available Analysis of sentinel lymph nodes (SLNs by means of One-Step Nucleic Acid Amplification (OSNA is gaining widespread use as a quick and accurate method. This assay detects the expression level of cytokeratin 19 (CK19 which is present in some but not all breast tumors. In this study, the clinical significance of negative CK19 was investigated in 219 cases of primary breast cancer. In 179 patients with clinically negative nodes, OSNA and imprint smear cytology of SLN were performed simultaneously. The OSNA revealed a node-positive rate of 24.6%. Negative CK19 correlated significantly with negative ER/PgR and higher Ki-67 values, and marginally with higher nuclear grade and p53 overexpression. The triple negative subtype showed lower CK19 expression. OSNA revealed that one of the negative CK19 cases was actually a false negative but this was corrected with the use of the imprint smear cytology. In conclusion, CK19 negativity reflected the aggressiveness of primary breast cancer. OSNA assay used to analyze SLN was useful, but there is a possibility that it will mistakenly detect false negatives in CK19 negative tumors. Therefore, in tumors with negative CK19, the imprint smear cytology may be more useful in cases with macrometastasis.

Clinical Significance of CK19 Negative Breast Cancer

International Nuclear Information System (INIS)

Fujisue, Mamiko; Nishimura, Reiki; Okumura, Yasuhiro; Tashima, Rumiko; Nishiyama, Yasuyuki; Osako, Tomofumi; Toyozumi, Yasuo; Arima, Nobuyuki

2012-01-01

Analysis of sentinel lymph nodes (SLNs) by means of One-Step Nucleic Acid Amplification (OSNA) is gaining widespread use as a quick and accurate method. This assay detects the expression level of cytokeratin 19 (CK19) which is present in some but not all breast tumors. In this study, the clinical significance of negative CK19 was investigated in 219 cases of primary breast cancer. In 179 patients with clinically negative nodes, OSNA and imprint smear cytology of SLN were performed simultaneously. The OSNA revealed a node-positive rate of 24.6%. Negative CK19 correlated significantly with negative ER/PgR and higher Ki-67 values, and marginally with higher nuclear grade and p53 overexpression. The triple negative subtype showed lower CK19 expression. OSNA revealed that one of the negative CK19 cases was actually a false negative but this was corrected with the use of the imprint smear cytology. In conclusion, CK19 negativity reflected the aggressiveness of primary breast cancer. OSNA assay used to analyze SLN was useful, but there is a possibility that it will mistakenly detect false negatives in CK19 negative tumors. Therefore, in tumors with negative CK19, the imprint smear cytology may be more useful in cases with macrometastasis

Enzalutamide for the Treatment of Androgen Receptor-Expressing Triple-Negative Breast Cancer.

Science.gov (United States)

Traina, Tiffany A; Miller, Kathy; Yardley, Denise A; Eakle, Janice; Schwartzberg, Lee S; O'Shaughnessy, Joyce; Gradishar, William; Schmid, Peter; Winer, Eric; Kelly, Catherine; Nanda, Rita; Gucalp, Ayca; Awada, Ahmad; Garcia-Estevez, Laura; Trudeau, Maureen E; Steinberg, Joyce; Uppal, Hirdesh; Tudor, Iulia Cristina; Peterson, Amy; Cortes, Javier

2018-03-20

Purpose Studies suggest that a subset of patients with triple-negative breast cancer (TNBC) have tumors that express the androgen receptor (AR) and may benefit from an AR inhibitor. This phase II study evaluated the antitumor activity and safety of enzalutamide in patients with locally advanced or metastatic AR-positive TNBC. Patients and Methods Tumors were tested for AR with an immunohistochemistry assay optimized for breast cancer; nuclear AR staining > 0% was considered positive. Patients received enzalutamide 160 mg once per day until disease progression. The primary end point was clinical benefit rate (CBR) at 16 weeks. Secondary end points included CBR at 24 weeks, progression-free survival, and safety. End points were analyzed in all enrolled patients (the intent-to-treat [ITT] population) and in patients with one or more postbaseline assessment whose tumor expressed ≥ 10% nuclear AR (the evaluable subgroup). Results Of 118 patients enrolled, 78 were evaluable. CBR at 16 weeks was 25% (95% CI, 17% to 33%) in the ITT population and 33% (95% CI, 23% to 45%) in the evaluable subgroup. Median progression-free survival was 2.9 months (95% CI, 1.9 to 3.7 months) in the ITT population and 3.3 months (95% CI, 1.9 to 4.1 months) in the evaluable subgroup. Median overall survival was 12.7 months (95% CI, 8.5 months to not yet reached) in the ITT population and 17.6 months (95% CI, 11.6 months to not yet reached) in the evaluable subgroup. Fatigue was the only treatment-related grade 3 or higher adverse event with an incidence of > 2%. Conclusion Enzalutamide demonstrated clinical activity and was well tolerated in patients with advanced AR-positive TNBC. Adverse events related to enzalutamide were consistent with its known safety profile. This study supports additional development of enzalutamide in advanced TNBC.

Expression of the CDR1 efflux pump in clinical Candida albicans isolates is controlled by a negative regulatory element

International Nuclear Information System (INIS)

Gaur, Naseem Akhtar; Manoharlal, Raman; Saini, Preeti; Prasad, Tulika; Mukhopadhyay, Gauranga; Hoefer, Milan; Morschhaeuser, Joachim; Prasad, Rajendra

2005-01-01

Resistance to azole antifungal drugs in clinical isolates of the human fungal pathogen Candida albicans is often caused by constitutive overexpression of the CDR1 gene, which encodes a multidrug efflux pump of the ABC transporter superfamily. To understand the relevance of a recently identified negative regulatory element (NRE) in the CDR1 promoter for the control of CDR1 expression in the clinical scenario, we investigated the effect of mutation or deletion of the NRE on CDR1 expression in two matched pairs of azole-sensitive and resistant clinical isolates of C. albicans. Expression of GFP or lacZ reporter genes from the wild type CDR1 promoter was much higher in the azole-resistant C. albicans isolates than in the azole-susceptible isolates, reflecting the known differences in CDR1 expression in these strains. Deletion or mutation of the NRE resulted in enhanced reporter gene expression in azole-sensitive strains, but did not further increase the already high CDR1 promoter activity in the azole-resistant strains. In agreement with these findings, electrophoretic mobility shift assays showed a reduced binding to the NRE of nuclear extracts from the resistant C. albicans isolates as compared with extracts from the sensitive isolates. These results demonstrate that the NRE is involved in maintaining CDR1 expression at basal levels and that this repression is overcome in azole-resistant clinical C. albicans isolates, resulting in constitutive CDR1 overexpression and concomitant drug resistance

[Negative symptoms in schizophrenia: psychotherapeutic approaches].

Science.gov (United States)

Azorin, J-M; Adida, M; Belzeaux, R; Pringuey, D; Micoulaud Franchi, J-A; Simon, N; Cermolacce, M; Kaladjian, A; Fakra, E

2015-12-01

Although negative symptoms are recognized as a central feature of schizophrenia, their definition as well as phenomenology have long been a vexing issue. During these last years, a major progress has been made with the delineation of two underlying subdomains of negative symptoms: diminished expression and anhedonia-avolition-apathy. As current guidelines are not always in accord on the efficacy of treatments on negative symptoms, it may be tempting to re-interpret the findings of clinical trials by looking at the effects of treatments on these two subdomains. This could concern both psychotropic treatments and psychotherapeutic interventions. Furthermore, neuroimaging as well as emotional response studies have permitted to better understand the mechanism which could be at the root of diminished expression and anhedonia in schizophrenia. On this basis, new psychotherapeutic methods have been devised which, by specifically targeting these two subdomains, are likely to be more efficient on negative symptoms. Further research is warranted to test their efficacy in randomized controlled trials. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Relationship Between Quantitative GRB7 RNA Expression and Recurrence after Adjuvant Anthracycline Chemotherapy in Triple Negative Breast Cancer

Science.gov (United States)

Sparano, Joseph A.; Goldstein, Lori J.; Childs, Barrett H.; Shak, Steven; Brassard, Diana; Badve, Sunil; Baehner, Frederick L.; Bugarini, Roberto; Rowley, Steve; Perez, Edith; Shulman, Lawrence N.; Martino, Silvana; Davidson, Nancy E.; Kenny, Paraic A.; Sledge, George W.; Gray, Robert

2012-01-01

Purpose To perform an exploratory analysis of the relationship between gene expression and recurrence in patients with operable triple negative breast cancer (TNBC) treated with adjuvant doxorubicin-containing chemotherapy. Experimental design RNA was extracted from archived tumor samples derived from 246 patients with stage I-III TNBC treated with adjuvant doxorubicin-containing chemotherapy, and was analyzed by quantitative RT-PCR for a panel of 374 genes. The relationship between gene expression and recurrence was evaluated using weighted Cox proportional hazards model score tests. Results GRB7 was the only gene for which higher expression was significantly associated with increased recurrence in TNBC (Korn’s adjusted p value=0.04). In a Cox proportional hazards model adjusted for clinicopathologic features, higher GRB7 expression was associated with an increased recurrence risk (HR 2.31, p=0.04 using the median as the split). The 5-year recurrence rates were 10.5% (95% confidence intervals [CI] 7.8%, 14.1%) in the low and 20.4% (95% CI 16.5%, 25.0%) in the high GRB7 groups. External validation in other datasets indicated that GRB7 expression was not prognostic in two adjuvant trials including variable systemic therapy, but in two other trials showed that high GBR7 expression was associated with resistance to neoadjuvant doxorubicin and taxane therapy. Conclusions GRB7 was associated with an increased risk of recurrence in TNBC, suggesting that GRB7 or GRB7-dependent pathways may serve as potential biomarkers for therapeutic targets. Therapeutic targeting of one or more factors identified which function as interaction nodes or effectors should also be considered. PMID:21933890

Relationship between quantitative GRB7 RNA expression and recurrence after adjuvant anthracycline chemotherapy in triple-negative breast cancer.

Science.gov (United States)

Sparano, Joseph A; Goldstein, Lori J; Childs, Barrett H; Shak, Steven; Brassard, Diana; Badve, Sunil; Baehner, Frederick L; Bugarini, Roberto; Rowley, Steve; Perez, Edith A; Shulman, Lawrence N; Martino, Silvana; Davidson, Nancy E; Kenny, Paraic A; Sledge, George W; Gray, Robert

2011-11-15

To conduct an exploratory analysis of the relationship between gene expression and recurrence in patients with operable triple-negative breast cancer (TNBC) treated with adjuvant doxorubicin-containing chemotherapy. RNA was extracted from archived tumor samples derived from 246 patients with stage I-III TNBC treated with adjuvant doxorubicin-containing chemotherapy, and was analyzed by quantitative reverse transcriptase PCR for a panel of 374 genes. The relationship between gene expression and recurrence was evaluated using weighted Cox proportional hazards model score tests. Growth factor receptor bound protein 7 (GRB7) was the only gene for which higher expression was significantly associated with increased recurrence in TNBC (Korn's adjusted P value = 0.04). In a Cox proportional hazards model adjusted for clinicopathologic features, higher GRB7 expression was associated with an increased recurrence risk (HR = 2.31; P = 0.04 using the median as the split). The 5-year recurrence rates were 10.5% [95% confidence intervals (CI), 7.8-14.1] in the low and 20.4% (95% CI, 16.5-25.0) in the high GRB7 groups. External validation in other datasets indicated that GRB7 expression was not prognostic in two adjuvant trials including variable systemic therapy, but in two other trials showed that high GBR7 expression was associated with resistance to neoadjuvant doxorubicin and taxane therapy. GRB7 was associated with an increased risk of recurrence in TNBC, suggesting that GRB7 or GRB7-dependent pathways may serve as potential biomarkers for therapeutic targets. Therapeutic targeting of one or more factors identified which function as interaction nodes or effectors should also be considered.

The Role of SPINK1 in ETS Rearrangement Negative Prostate Cancers

Science.gov (United States)

Tomlins, Scott A.; Rhodes, Daniel R.; Yu, Jianjun; Varambally, Sooryanarayana; Mehra, Rohit; Perner, Sven; Demichelis, Francesca; Helgeson, Beth E.; Laxman, Bharathi; Morris, David S.; Cao, Qi; Cao, Xuhong; Andrén, Ove; Fall, Katja; Johnson, Laura; Wei, John T.; Shah, Rajal B.; Al-Ahmadie, Hikmat; Eastham, James A.; Eggener, Scott E.; Fine, Samson W.; Hotakainen, Kristina; Stenman, Ulf-Håkan; Tsodikov, Alex; Gerald, William L.; Lilja, Hans; Reuter, Victor E.; Kantoff, Phillip W.; Scardino, Peter T.; Rubin, Mark A.; Bjartell, Anders S.; Chinnaiyan, Arul M.

2009-01-01

Summary ETS gene fusions have been characterized in a majority of prostate cancers, however the key molecular alterations in ETS negative cancers are unclear. Here we used an outlier meta-analysis (meta-COPA) to identify SPINK1 outlier-expression exclusively in a subset of ETS rearrangement negative cancers (~10% of total cases). We validated the mutual exclusivity of SPINK1 expression and ETS fusion status, demonstrated that SPINK1 outlier-expression can be detected non-invasively in urine and observed that SPINK1 outlier-expression is an independent predictor of biochemical recurrence after resection. We identified the aggressive 22RV1 cell line as a SPINK1 outlier-expression model, and demonstrate that SPINK1 knockdown in 22RV1 attenuates invasion, suggesting a functional role in ETS rearrangement negative prostate cancers. PMID:18538735

Outcome of intracranial electroencephalography monitoring and surgery in magnetic resonance imaging-negative temporal lobe epilepsy.

Science.gov (United States)

Lee, Ricky W; Hoogs, Marietta M; Burkholder, David B; Trenerry, Max R; Drazkowski, Joseph F; Shih, Jerry J; Doll, Karey E; Tatum, William O; Cascino, Gregory D; Marsh, W Richard; Wirrell, Elaine C; Worrell, Gregory A; So, Elson L

2014-07-01

We evaluated the outcomes of intracranial electroencephalography (iEEG) recording and subsequent resective surgery in patients with magnetic resonance imaging (MRI)-negative temporal lobe epilepsy (TLE). Thirty-two patients were identified from the Mayo Clinic Epilepsy Surgery Database (Arizona, Florida, and Minnesota). Eight (25.0%) had chronic iEEG monitoring that recorded neocortical temporal seizure onsets; 12 (37.5%) had mesial temporal seizure onsets; 5 (15.6%) had independent neocortical and mesial temporal seizure onsets; and 7 (21.9%) had simultaneous neocortical and mesial seizure onsets. Neocortical temporal lobe seizure semiology was the only factor significantly associated with neocortical temporal seizure onsets on iEEG. Only 33.3% of patients who underwent lateral temporal neocorticectomy had an Engel class 1 outcome, whereas 76.5% of patients with iEEG-guided anterior temporal lobectomy that included the amygdala and the hippocampus had an Engel class 1 outcome. Limitations in cohort size precluded statistical analysis of neuropsychological test data. Copyright © 2014 Elsevier B.V. All rights reserved.

Neopterin negatively regulates expression of ABCA1 and ABCG1 by the LXRα signaling pathway in THP-1 macrophage-derived foam cells.

Science.gov (United States)

Yan, Jin-quan; Tan, Chun-zhi; Wu, Jin-hua; Zhang, Dong-cui; Chen, Ji-ling; Zeng, Bin-yuan; Jiang, Yu-ping; Nie, Jin; Liu, Wei; Liu, Qin; Dai, Hao

2013-07-01

To investigate the effects of neopterin on ABCA1 expression and cholesterol efflux in human THP-1 macrophage-derived foam cells, and to explore the role of the liver X receptor alpha (LXRα) involved. In the present study, THP-1 cells were pre-incubated with ox-LDL to become foam cells. The protein and mRNA expression were examined by Western blot assays and real-time quantitative PCR, respectively. Liquid scintillation counting and high performance liquid chromatography assays were used to test cellular cholesterol efflux and cholesterol content. Neopterin decreased ABCA1 expression and cholesterol efflux in a time- and concentration-dependent manner in THP-1 macrophage-derived foam cells, and the LXRα siRNA can reverse the inhibitory effects induced by neopterin. Neoterin has a negative regulation on ABCA1 expression via the LXRα signaling pathway, which suggests the aggravated effects of neopterin on atherosclerosis.

The Sisyphean myth, negative capability and societal relevance ...

African Journals Online (AJOL)

Different forms of literature over the years have expressed mankind's views, thoughts, notions, beliefs, and inclinations. The feelings of futility, negativity, absurdism, nihilism expressed in the myth of Sisyphus is just one of the numerous representations that literature can offer. But not all literary expressions are posers of ...

Keratin 17 is overexpressed and predicts poor survival in estrogen receptor-negative/human epidermal growth factor receptor-2-negative breast cancer.

Science.gov (United States)

Merkin, Ross D; Vanner, Elizabeth A; Romeiser, Jamie L; Shroyer, A Laurie W; Escobar-Hoyos, Luisa F; Li, Jinyu; Powers, Robert S; Burke, Stephanie; Shroyer, Kenneth R

2017-04-01

Clinicopathological features of breast cancer have limited accuracy to predict survival. By immunohistochemistry (IHC), keratin 17 (K17) expression has been correlated with triple-negative status (estrogen receptor [ER]/progesterone receptor/human epidermal growth factor receptor-2 [HER2] negative) and decreased survival, but K17 messenger RNA (mRNA) expression has not been evaluated in breast cancer. K17 is a potential prognostic cancer biomarker, targeting p27, and driving cell cycle progression. This study compared K17 protein and mRNA expression to ER/progesterone receptor/HER2 receptor status and event-free survival. K17 IHC was performed on 164 invasive breast cancers and K17 mRNA was evaluated in 1097 breast cancers. The mRNA status of other keratins (16/14/9) was evaluated in 113 ER - /HER2 - ductal carcinomas. IHC demonstrated intense cytoplasmic and membranous K17 localization in myoepithelial cells of benign ducts and lobules and tumor cells of ductal carcinoma in situ. In ductal carcinomas, K17 protein was detected in most triple-negative tumors (28/34, 82%), some non-triple-negative tumors (52/112, 46%), but never in lobular carcinomas (0/15). In ductal carcinomas, high K17 mRNA was associated with reduced 5-year event-free survival in advanced tumor stage (n = 149, hazard ratio [HR] = 3.68, P = .018), and large (n = 73, HR = 3.95, P = .047), triple-negative (n = 103, HR = 2.73, P = .073), and ER - /HER2 - (n = 113, HR = 2.99, P = .049) tumors. There were significant correlations among keratins 17, 16, 14, and 9 mRNA levels suggesting these keratins (all encoded on chromosome 17) could be coordinately expressed in breast cancer. Thus, K17 is expressed in a subset of triple-negative breast cancers, and is a marker of poor prognosis in patients with advanced stage and ER - /HER2 - breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Elevated endogenous expression of the dominant negative basic helix-loop-helix protein ID1 correlates with significant centrosome abnormalities in human tumor cells

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Gutmann Anja

2010-01-01

Full Text Available Abstract Background ID proteins are dominant negative inhibitors of basic helix-loop-helix transcription factors that have multiple functions during development and cellular differentiation. Ectopic (over-expression of ID1 extends the lifespan of primary human epithelial cells. High expression levels of ID1 have been detected in multiple human malignancies, and in some have been correlated with unfavorable clinical prognosis. ID1 protein is localized at the centrosomes and forced (over-expression of ID1 results in errors during centrosome duplication. Results Here we analyzed the steady state expression levels of the four ID-proteins in 18 tumor cell lines and assessed the number of centrosome abnormalities. While expression of ID1, ID2, and ID3 was detected, we failed to detect protein expression of ID4. Expression of ID1 correlated with increased supernumerary centrosomes in most cell lines analyzed. Conclusions This is the first report that shows that not only ectopic expression in tissue culture but endogenous levels of ID1 modulate centrosome numbers. Thus, our findings support the hypothesis that ID1 interferes with centrosome homeostasis, most likely contributing to genomic instability and associated tumor aggressiveness.

Enhanced Feedback-Related Negativity in Alzheimer’s Disease

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Shuhei Yamaguchi

2017-04-01

Full Text Available Alzheimer’s disease (AD, the most common cause of dementia in the elderly, results in the impairment of executive function, including that of performance monitoring. Feedback-related negativity (FRN is an electrophysiological measure reflecting the activity of this monitoring system via feedback signals, and is generated from the anterior cingulate cortex. However, there have been no reports on FRN in AD. Based on prior aging studies, we hypothesized that FRN would decrease in AD patients. To assess this, FRN was measured in healthy individuals and those with AD during a simple gambling task involving positive and negative feedback stimuli. Contrary to our hypothesis, FRN amplitude increased in AD patients, compared with the healthy elderly. We speculate that this may reflect the existence of a compensatory mechanism against the decline in executive function. Also, there was a significant association between FRN amplitude and depression scores in AD, and the FRN amplitude tended to increase insomuch as the Self-rating Depression Scale (SDS was higher. This result suggests the existence of a negative bias in the affective state in AD. Thus, the impaired functioning monitoring system in AD is a more complex phenomenon than we thought.

Leukocyte-associated immunoglobulin-like receptor-1 is expressed on human megakaryocytes and negatively regulates the maturation of primary megakaryocytic progenitors and cell line

International Nuclear Information System (INIS)

Xue, Jiangnan; Zhang, Xiaoshu; Zhao, Haiya; Fu, Qiang; Cao, Yanning; Wang, Yuesi; Feng, Xiaoying; Fu, Aili

2011-01-01

Research highlights: → LAIR-1 is expressed on human megakaryocytes from an early stage. → Up-regulation of LAIR-1 negatively regulates megakaryocytic differentiation of cell line. → LAIR-1 negatively regulates the differentiation of primary megakaryocytic progenitors. -- Abstract: Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is an inhibitory collagen receptor which belongs to the immunoglobulin (Ig) superfamily. Although the inhibitory function of LAIR-1 has been extensively described in multiple leukocytes, its role in megakaryocyte (MK) has not been explored so far. Here, we show that LAIR-1 is expressed on human bone marrow CD34 + CD41a + and CD41a + CD42b + cells. LAIR-1 is also detectable in a fraction of human cord blood CD34 + cell-derived MK that has morphological characteristics of immature MK. In megakaryoblastic cell line Dami, the membrane protein expression of LAIR-1 is up-regulated significantly when cells are treated with phorbol ester phorbol 12-myristate 13-acetate (PMA). Furthermore, cross-linking of LAIR-1 in Dami cells with its natural ligand or anti-LAIR-1 antibody leads to the inhibition of cell proliferation and PMA-promoted differentiation when examined by the MK lineage-specific markers (CD41a and CD42b) and polyploidization. In addition, we also observed that cross-linking of LAIR-1 results in decreased MK generation from primary human CD34 + cells cultured in a cytokines cocktail that contains TPO. These results suggest that LAIR-1 is a likely candidate for an early marker of MK differentiation, and provide initial evidence indicating that LAIR-1 serves as a negative regulator of megakaryocytopoiesis.

Immunohistochemical Characteristics of Triple Negative/Basal-like Breast Cancer

OpenAIRE

Emel Ebru PALA; Ümit BAYOL; Süheyla CUMURCU; Elif KESKİN

2012-01-01

Objective: Triple-negative-breast-cancer that accounts for 10-20% of all breast carcinomas is defined by the lack of estrogen receptor, progesterone receptor, HER2 expression, and agressive clinical behavior. Triple-negative-breast-cancer is categorized into basal like and other types. The basal-like subtype is characterized by the expression of myoepithelial/basal markers.Material and Method: We studied 41 immunohistochemically triplenegative- breast-cancer patients to determine EGFR, Cytoke...

Molecular basis of the triple negative breast cancer

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Ayse Feyda Nursal

2015-06-01

Full Text Available Breast cancer is the most common type of cancer in women and more than 1 million breast cancer cases are diagnosed each year all over the world. Breast cancer is a complex and heterogeneous disease in terms of its molecular structure, mutation type, metastase properties, clinical course and therapeutic response. Breast cancer is divided into subtypes based on expression properties of molecular markers as estrogen receptor, progestron receptor, human epidermal growth factor receptor 2. Triple-negative breast cancer is characterized by the lack of tumors that estrogen receptor, progestron receptor, human epidermal growth factor receptor 2 gene expression. These type of tumors lead to agressive clinical course due to unresponsiveness to systemic endocrine therapy and poor prognosis. Triple negative breast cancer constitutes 10-20% of all breast cancers. It affects generally young and African-American women. Triple negative breast cancer have several subtypes based on the gene expression properties. The majority of them are basal-like breast cancers. In this review, current literature is revised and summarized with respect to the molecular basis of triple negative cancers. [Archives Medical Review Journal 2015; 24(2.000: 251-259

Prognostic Value of Molecular Subtypes, Ki67 Expression and Impact of Postmastectomy Radiation Therapy in Breast Cancer Patients With Negative Lymph Nodes After Mastectomy

International Nuclear Information System (INIS)

Selz, Jessica; Stevens, Denise; Jouanneau, Ludivine; Labib, Alain; Le Scodan, Romuald

2012-01-01

Purpose: To determine whether Ki67 expression and breast cancer subtypes could predict locoregional recurrence (LRR) and influence the postmastectomy radiotherapy (PMRT) decision in breast cancer (BC) patients with pathologic negative lymph nodes (pN0) after modified radical mastectomy (MRM). Methods and Materials: A total of 699 BC patients with pN0 status after MRM, treated between 2001 and 2008, were identified from a prospective database in a single institution. Tumors were classified by intrinsic molecular subtype as luminal A or B, HER2+, and triple-negative (TN) using estrogen, progesterone, and HER2 receptors. Multivariate Cox analysis was used to determine the risk of LRR associated with intrinsic subtypes and Ki67 expression, adjusting for known prognostic factors. Results: At a median follow-up of 56 months, 17 patients developed LRR. Five-year LRR-free survival and overall survival in the entire population were 97%, and 94.7%, respectively, with no difference between the PMRT (n=191) and no-PMRT (n=508) subgroups. No constructed subtype was associated with an increased risk of LRR. Ki67 >20% was the only independent prognostic factor associated with increased LRR (hazard ratio, 4.18; 95% CI, 1.11-15.77; P<.0215). However, PMRT was not associated with better locoregional control in patients with proliferative tumors. Conclusions: Ki67 expression but not molecular subtypes are predictors of locoregional recurrence in breast cancer patients with negative lymph nodes after MRM. The benefit of adjuvant RT in patients with proliferative tumors should be further investigated in prospective studies.

Prognostic Value of Molecular Subtypes, Ki67 Expression and Impact of Postmastectomy Radiation Therapy in Breast Cancer Patients With Negative Lymph Nodes After Mastectomy

Energy Technology Data Exchange (ETDEWEB)

Selz, Jessica, E-mail: chaumontjessica@yahoo.fr [Department of Radiation Oncology, Institut Curie, Hopital Rene Huguenin, Saint Cloud (France); Stevens, Denise; Jouanneau, Ludivine [Department of Medical Statistics, Institut Curie, Hopital Rene Huguenin, Saint Cloud (France); Labib, Alain [Department of Radiation Oncology, Institut Curie, Hopital Rene Huguenin, Saint Cloud (France); Le Scodan, Romuald [Department of Radiation Oncology, Centre Hospitalier Prive Saint Gregoire, Saint Gregoire (France)

2012-12-01

Purpose: To determine whether Ki67 expression and breast cancer subtypes could predict locoregional recurrence (LRR) and influence the postmastectomy radiotherapy (PMRT) decision in breast cancer (BC) patients with pathologic negative lymph nodes (pN0) after modified radical mastectomy (MRM). Methods and Materials: A total of 699 BC patients with pN0 status after MRM, treated between 2001 and 2008, were identified from a prospective database in a single institution. Tumors were classified by intrinsic molecular subtype as luminal A or B, HER2+, and triple-negative (TN) using estrogen, progesterone, and HER2 receptors. Multivariate Cox analysis was used to determine the risk of LRR associated with intrinsic subtypes and Ki67 expression, adjusting for known prognostic factors. Results: At a median follow-up of 56 months, 17 patients developed LRR. Five-year LRR-free survival and overall survival in the entire population were 97%, and 94.7%, respectively, with no difference between the PMRT (n=191) and no-PMRT (n=508) subgroups. No constructed subtype was associated with an increased risk of LRR. Ki67 >20% was the only independent prognostic factor associated with increased LRR (hazard ratio, 4.18; 95% CI, 1.11-15.77; P<.0215). However, PMRT was not associated with better locoregional control in patients with proliferative tumors. Conclusions: Ki67 expression but not molecular subtypes are predictors of locoregional recurrence in breast cancer patients with negative lymph nodes after MRM. The benefit of adjuvant RT in patients with proliferative tumors should be further investigated in prospective studies.

Decreased BECN1 mRNA Expression in Human Breast Cancer is Associated With Estrogen Receptor-Negative Subtypes and Poor Prognosis

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Hao Tang

2015-03-01

Full Text Available Both BRCA1 and Beclin 1 (BECN1 are tumor suppressor genes, which are in close proximity on the human chromosome 17q21 breast cancer tumor susceptibility locus and are often concurrently deleted. However, their importance in sporadic human breast cancer is not known. To interrogate the effects of BECN1 and BRCA1 in breast cancer, we studied their mRNA expression patterns in breast cancer patients from two large datasets: The Cancer Genome Atlas (TCGA (n = 1067 and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC (n = 1992. In both datasets, low expression of BECN1 was more common in HER2-enriched and basal-like (mostly triple-negative breast cancers compared to luminal A/B intrinsic tumor subtypes, and was also strongly associated with TP53 mutations and advanced tumor grade. In contrast, there was no significant association between low BRCA1 expression and HER2-enriched or basal-like subtypes, TP53 mutations or tumor grade. In addition, low expression of BECN1 (but not low BRCA1 was associated with poor prognosis, and BECN1 (but not BRCA1 expression was an independent predictor of survival. These findings suggest that decreased mRNA expression of the autophagy gene BECN1 may contribute to the pathogenesis and progression of HER2-enriched, basal-like, and TP53 mutant breast cancers.

Analyzing THE PLACE FOR THE EVENT-type Metonymies from the Perspective of Negative Evaluative Factors

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Nami Arimitsu

Full Text Available This paper has two objectives. First, by analyzing THE PLACE FOR THE EVENT-type metonymies, this paper points out that it is mainly negative events that are expressed by this type of metonymy. Second, this paper reveals the motivations of those THE PLACE FOR THE EVENT-type metonymies that express negative events. Metonymies are widely investigated along with the views of Lakoff and Johnson (1980, and their oppositional semantic aspects are pointed out by Voßhagen (1999. However, none of the previous studies focused on the nature of THE PLACE FOR THE EVENT-type metonymies from the perspective of negative evaluation, euphemism, and politeness. "Let's not let Thailand become another Vietnam" expresses the Vietnam War and all the tragedies behind it. Speakers refrain from expressing negative evaluative aspects from a euphemistic perspective and try to behave politely through hiding the exact expression, and listeners can also easily understand THE PLACE FOR THE EVENT-type metonymies that express negative events, since negative events are much more highly marked and intensified, as well as more prominent, than are positive ones.

Amplification and high-level expression of heat shock protein 90 marks aggressive phenotypes of human epidermal growth factor receptor 2 negative breast cancer.

Science.gov (United States)

Cheng, Qing; Chang, Jeffrey T; Geradts, Joseph; Neckers, Leonard M; Haystead, Timothy; Spector, Neil L; Lyerly, H Kim

2012-04-17

Although human epidermal growth factor receptor 2 (HER2) positive or estrogen receptor (ER) positive breast cancers are treated with clinically validated anti-HER2 or anti-estrogen therapies, intrinsic and acquired resistance to these therapies appears in a substantial proportion of breast cancer patients and new therapies are needed. Identification of additional molecular factors, especially those characterized by aggressive behavior and poor prognosis, could prioritize interventional opportunities to improve the diagnosis and treatment of breast cancer. We compiled a collection of 4,010 breast tumor gene expression data derived from 23 datasets that have been posted on the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. We performed a genome-scale survival analysis using Cox-regression survival analyses, and validated using Kaplan-Meier Estimates survival and Cox Proportional-Hazards Regression survival analyses. We conducted a genome-scale analysis of chromosome alteration using 481 breast cancer samples obtained from The Cancer Genome Atlas (TCGA), from which combined expression and copy number data were available. We assessed the correlation between somatic copy number alterations and gene expression using analysis of variance (ANOVA). Increased expression of each of the heat shock protein (HSP) 90 isoforms, as well as HSP transcriptional factor 1 (HSF1), was correlated with poor prognosis in different subtypes of breast cancer. High-level expression of HSP90AA1 and HSP90AB1, two cytoplasmic HSP90 isoforms, was driven by chromosome coding region amplifications and were independent factors that led to death from breast cancer among patients with triple-negative (TNBC) and HER2-/ER+ subtypes, respectively. Furthermore, amplification of HSF1 was correlated with higher HSP90AA1 and HSP90AB1 mRNA expression among the breast cancer cells without amplifications of these two genes. A collection of HSP90AA1, HSP90AB1 and HSF

Expression of alkyl hydroperoxide reductase is regulated negatively by OxyR1 and positively by RpoE2 sigma factor in Azospirillum brasilense Sp7.

Science.gov (United States)

Singh, Sudhir; Dwivedi, Susheel Kumar; Singh, Vijay Shankar; Tripathi, Anil Kumar

2016-10-01

OxyR proteins are LysR-type transcriptional regulators, which play an important role in responding to oxidative stress in bacteria. Azospirillum brasilense Sp7 harbours two copies of OxyR. The inactivation of the oxyR1, the gene organized divergently to ahpC in A. brasilense Sp7, led to an increased tolerance to alkyl hydroperoxides, which was corroborated by an increase in alkyl hydroperoxide reductase (AhpC) activity, enhanced expression of ahpC :lacZ fusion and increased synthesis of AhpC protein in the oxyR1::km mutant. The upstream region of ahpC promoter harboured a putative OxyR binding site, T-N11-A. Mutation of T, A or both in the T-N11-Amotif caused derepression of ahpC in A. brasilense suggesting that T-N11-A might be the binding site for a negative regulator. Retardation of the electrophoretic mobility of the T-N11-A motif harbouring oxyR1-ahpC intergenic DNA by recombinant OxyR1, under reducing as well as oxidizing conditions, indicated that OxyR1 acts as a negative regulator of ahpC in A. brasilense. Sequence of the promoter of ahpC, predicted on the basis of transcriptional start site, and an enhanced expression of ahpC:lacZ fusion in chrR2::km mutant background suggested that ahpC promoter was RpoE2 dependent. Thus, this study shows that in A. brasilense Sp7, ahpC expression is regulated negatively by OxyR1 but is regulated positively by RpoE2, an oxidative-stress-responsive sigma factor. It also shows that OxyR1 regulates the expression RpoE1, which is known to play an important role during photooxidative stress in A. brasilense.

Differentially expressed miRNAs in triple negative breast cancer between African-American and non-Hispanic white women.

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Sugita, Bruna; Gill, Mandeep; Mahajan, Akanskha; Duttargi, Anju; Kirolikar, Saurabh; Almeida, Rodrigo; Regis, Kenny; Oluwasanmi, Olusayo L; Marchi, Fabio; Marian, Catalin; Makambi, Kepher; Kallakury, Bhaskar; Sheahan, Laura; Cavalli, Iglenir J; Ribeiro, Enilze M; Madhavan, Subha; Boca, Simina; Gusev, Yuriy; Cavalli, Luciane R

2016-11-29

Triple Negative Breast Cancer (TNBC), a clinically aggressive subtype of breast cancer, disproportionately affects African American (AA) women when compared to non-Hispanic Whites (NHW). MiRNAs(miRNAs) play a critical role in these tumors, through the regulation of cancer driver genes. In this study, our goal was to characterize and compare the patterns of miRNA expression in TNBC of AA (n = 27) and NHW women (n = 30). A total of 256 miRNAs were differentially expressed between these groups, and distinct from the ones observed in their respective non-TNBC subtypes. Fifty-five of these miRNAs were mapped in cytobands carrying copy number alterations (CNAs); 26 of them presented expression levels concordant with the observed CNAs. Receiving operating characteristic (ROC) analysis showed a good power (AUC ≥ 0.80; 95% CI) for over 65% of the individual miRNAs and a high combined power with superior sensitivity and specificity (AUC = 0.88 (0.78-0.99); 95% CI) of the 26 miRNA panel in discriminating TNBC between these populations. Subsequent miRNA target analysis revealed their involvement in the interconnected PI3K/AKT, MAPK and insulin signaling pathways. Additionally, three miRNAs of this panel were associated with early age at diagnosis. Altogether, these findings indicated that there are different patterns of miRNA expression between TNBC of AA and NHW women and that their mapping in genomic regions with high levels of CNAs is not merely physical, but biologically relevant to the TNBC phenotype. Once validated in distinct cohorts of AA women, this panel can potentially represent their intrinsic TNBC genome signature.

Evaluation of radiological detriment from negative radiological examinations

International Nuclear Information System (INIS)

Frometa Suarez, I.; Jerez Vergueria, S.F.

1997-01-01

The individul doses of radiation due to diagnostic radiology are usually low, though their contribution to the collective dose is very important given the large numbers of people exposed to these. This paper presents an analysis of the number of negative radiologiacl examinations in a major Cuban Hospital, and their contribution to the collective dose, and radiation organ and tissue, effective (expressed as severe hereditary effect and the occurrence of fatal and non fatal cancers) are all evaluated. The negative findings constitute 41 % of all examinations. The total contribution of negative examinations to the collective dose is very important given the large numbers of people exposed to these. This papaer presents an analysis of the number of negative radiological examinations in major Cuban Hospital, and their contribution to the collective dose of radiation. The absorbed dose by irradiation organ and tissue, effective dose equivalent, collective dose, and radiation risk (expressed as severe herditary effect and the occureence of fatal and non fatal cancers) are all evaluated. The negative findings constitute 41% of all examinations. The total contribution of negative examinations. The total contribution of negative examinations to the collective dose are found to make up 52.9 %: 11.35 Sv-man in the studied population

The expression of dominant negative TCF7L2 in pancreatic beta cells during the embryonic stage causes impaired glucose homeostasis.

Science.gov (United States)

Shao, Weijuan; Xiong, Xiaoquan; Ip, Wilfred; Xu, Fenghao; Song, Zhuolun; Zeng, Kejing; Hernandez, Marcela; Liang, Tao; Weng, Jianping; Gaisano, Herbert; Nostro, M Cristina; Jin, Tianru

2015-04-01

Disruption of TCF7L2 in mouse pancreatic β-cells has generated different outcomes in several investigations. Here we aim to clarify role of β-cell TCF7L2 and Wnt signaling using a functional-knockdown approach. Adenovirus-mediated dominant negative TCF7L2 (TCF7L2DN) expression was conducted in Ins-1 cells. The fusion gene in which TCF7L2DN expression is driven by P TRE3G was utilized to generate the transgenic mouse line TCF7L2DN Tet . The double transgenic line was created by mating TCF7L2DN Tet with Ins2-rtTA, designated as βTCFDN. β-cell specific TCF7L2DN expression was induced in βTCFDN by doxycycline feeding. TCF7L2DN expression in Ins-1 cells reduced GSIS, cell proliferation and expression of a battery of genes including incretin receptors and β-cell transcription factors. Inducing TCF7L2DN expression in βTCFDN during adulthood or immediately after weaning generated no or very modest metabolic defect, while its expression during embryonic development by doxycycline feeding in pregnant mothers resulted in significant glucose intolerance associated with altered β-cell gene expression and reduced β-cell mass. Our observations support a cell autonomous role for TCF7L2 in pancreatic β-cells suggested by most, though not all, investigations. βTCFDN is a novel model for further exploring the role of TCF7L2 in β-cell genesis and metabolic homeostasis.

Low/Negative Expression of PDGFR-α Identifies the Candidate Primary Mesenchymal Stromal Cells in Adult Human Bone Marrow

Directory of Open Access Journals (Sweden)

Hongzhe Li

2014-12-01

Full Text Available Human bone marrow (BM contains a rare population of nonhematopoietic mesenchymal stromal cells (MSCs, which are of central importance for the hematopoietic microenvironment. However, the precise phenotypic definition of these cells in adult BM has not yet been reported. In this study, we show that low/negative expression of CD140a (PDGFR-α on lin−/CD45−/CD271+ BM cells identified a cell population with very high MSC activity, measured as fibroblastic colony-forming unit frequency and typical in vitro and in vivo stroma formation and differentiation capacities. Furthermore, these cells exhibited high levels of genes associated with mesenchymal lineages and HSC supportive function. Moreover, lin−/CD45−/CD271+/CD140alow/− cells effectively mediated the ex vivo expansion of transplantable CD34+ hematopoietic stem cells. Taken together, these data indicate that CD140a is a key negative selection marker for adult human BM-MSCs, which enables to prospectively isolate a close to pure population of candidate human adult stroma stem/progenitor cells with potent hematopoiesis-supporting capacity.

An Attributional Analysis of Reactions to Negative Emotions.

Science.gov (United States)

Karasawa, Kaori

1995-01-01

Three studies examined observers' attributions and reactions to negative emotional displays, as well as expressers' expectations about others' reactions. Analysis revealed that people attribute others' negative emotions equally to situational factors and dispositions, whereas their own emotions are attributed to the situation more than to…

Corrugator Activity Confirms Immediate Negative Affect in Surprise

Directory of Open Access Journals (Sweden)

Sascha eTopolinski

2015-02-01

Full Text Available The emotion of surprise entails a complex of immediate responses, such as cognitive interruption, attention allocation to, and more systematic processing of the surprising stimulus. All these processes serve the ultimate function to increase processing depth and thus cognitively master the surprising stimulus. The present account introduces phasic negative affect as the underlying mechanism responsible for these consequences. Surprising stimuli are schema-discrepant and thus entail cognitive disfluency, which elicits immediate negative affect. This affect in turn works like a phasic cognitive tuning switching the current processing mode from more automatic and heuristic to more systematic and reflective processing. Directly testing the initial elicitation of negative affect by suprising events, the present experiment presented high and low surprising neutral trivia statements to N = 28 participants while assessing their spontaneous facial expressions via facial electromyography. High compared to low suprising trivia elicited higher corrugator activity, indicative of negative affect and mental effort, while leaving zygomaticus (positive affect and frontalis (cultural surprise expression activity unaffected. Future research shall investigate the mediating role of negative affect in eliciting surprise-related outcomes.

Negative Symptom Dimensions of the Positive and Negative Syndrome Scale Across Geographical Regions: Implications for Social, Linguistic, and Cultural Consistency

OpenAIRE

Khan, Anzalee; Liharska, Lora; Harvey, Philip D.; Atkins, Alexandra; Ulshen, Daniel; Keefe, Richard S.E.

2017-01-01

Objective: Recognizing the discrete dimensions that underlie negative symptoms in schizophrenia and how these dimensions are understood across localities might result in better understanding and treatment of these symptoms. To this end, the objectives of this study were to 1) identify the Positive and Negative Syndrome Scale negative symptom dimensions of expressive deficits and experiential deficits and 2) analyze performance on these dimensions over 15 geographical regions to determine whet...

[Expression and clinical significance of Pokemon in non-small cell lung cancer].

Science.gov (United States)

Zhao, Zhihong; Wang, Shengfa; Zhang, Tiewa

2007-12-20

Proto-oncogene Pokemon is the special transcription inhibitor of ARF,which can regulate cell growth and differentiation by ARF-P53 path.It may be the important monitoring target of tumor because of being upstream region of many tumor suppressor genes and proto-oncogenes.The aim of this study is to explore the clinical significance of Pokemon gene in non-small cell lung cancer(NSCLC). Immunohistochemistry was applied to detect the expression of Pokemon protein in 92 cases of NSCLC and 20 cases of paracancerous lung tissues.Correlation between abnormal expression of Pokemon with pathologic characteristics and prognosis of NSCLC was analyzed. Pokemon was not expressed in paracancerous lung tissues and was found in 66 of 92(71.7%) cases of lung cancer tissues.Expression of Pokemon was closely related to TNM stages(P=0.011).Survival rate of patients with negative Pokemon expression was significantly higher than that of those with positive Pokemon expression(P=0.0015).Pokemon expression was demonstrated as independent prognostic factor of NSCLC. Pokemon is expressed in NSCLC and it may be identified as a new diagnostic marker.High expression of Pokemon may indicate poor prognosis of patients with NSCLC.

An improved value for the electron affinity of the negative hydrogen ion

International Nuclear Information System (INIS)

Scherk, L.R.

1979-01-01

An expression is derived for the lifetime of a negative ion in a weak and static electric field. Using this expression, existing experimental data are analyzed to improve the empirical value of the electron affinity of the negative hydrogen ion by an order of magnitude. (author)

[Immunohistochemical characteristics of triple negative/basal-like breast cancer].

Science.gov (United States)

Pala, Emel Ebru; Bayol, Ümit; Cumurcu, Süheyla; Keskın, Elif

2012-01-01

Triple-negative-breast-cancer that accounts for 10-20% of all breast carcinomas is defined by the lack of estrogen receptor, progesterone receptor, HER2 expression, and agressive clinical behavior. Triple-negative-breast-cancer is categorized into basal like and other types. The basal-like subtype is characterized by the expression of myoepithelial/basal markers. We studied 41 immunohistochemically triplenegative- breast-cancer patients to determine EGFR, Cytokeratine 5/6, p53, Ki67, GCDFP-15 expression profiles, HER2 and Chromosome 17 centromere gene status by fluorescence-in-situ-hybridization method. Histological type was invasive ductal carcinoma in 90.2% of the tumors. p53, Ki67, GCDFP-15 mean positivity rates were 55.6%, 51.7%, and 3.2%, respectively. GCDFP-15 positivity was noted in 8 cases of which 6 were Cytokeratine 5/6 negative. The cut-off value for Cytokeratine 5/6 positivity was 5%. EGFR immunoreactivity was grouped into 0, 1+ as negative; 2+, 3+ as positive categories. Cytokeratine 5/6 was positive in 56,1%, EGFR was positive in 51.2% of the patients. The relation between Cytokeratine 5/6 and EGFR expression was statistically significant (p < 0.01). None of the cases showed HER2 amplification by fluorescence-in-situ-hybridization method. GCDFP-15 alone is not a useful marker to detect the metastasis of basaloid type breast cancers. Cytokeratine 5/6 and EGFR expressions showed correlation so these markers are reliable to diagnose basaloid type tumors with a 5% cut-off value.

The nature of the verbal self-monitor

NARCIS (Netherlands)

Ganushchak, Aleksandra (Lesya) Yurievna

2008-01-01

This thesis investigated the correlates of verbal self-monitoring in healthy adults. The central questions addressed in the thesis are: Does verbal monitoring work in a similar way as action monitoring? If the Error-Related Negativity (ERN) is associated with error processing in action monitoring,

Treatment for Negative Symptoms in Schizophrenia: A Comprehensive Review

NARCIS (Netherlands)

Veerman, Selene R. T.; Schulte, Peter F. J.; de Haan, Lieuwe

2017-01-01

Negative symptoms (such as amotivation and diminished expression) associated with schizophrenia are a major health concern. Adequate treatment would mean important progress with respect to quality of life and participation in society. Distinguishing primary from secondary negative symptoms may

Individual negative symptoms and domains - Relevance for assessment, pathomechanisms and treatment.

Science.gov (United States)

Kaiser, Stefan; Lyne, John; Agartz, Ingrid; Clarke, Mary; Mørch-Johnsen, Lynn; Faerden, Ann

2017-08-01

The negative symptoms of schizophrenia can be divided into two domains. Avolition/apathy includes the individual symptoms of avolition, asociality and anhedonia. Diminished expression includes blunted affect and alogia. Until now, causes and treatment of negative symptoms have remained a major challenge, which is partially related to the focus on negative symptoms as a broad entity. Here, we propose that negative symptoms may become more tractable when the different domains and individual symptoms are taken into account. There is now increasing evidence that the relationship with clinical variables - in particular outcome - differs between the domains of avolition/apathy and diminished expression. Regarding models of negative symptom formation, those relevant to avolition/apathy are now converging on processes underlying goal-directed behavior and dysfunctions of the reward system. In contrast, models of the diminished expression domains are only beginning to emerge. The aim of this article is to review the specific clinical, behavioral and neural correlates of individual symptoms and domains as a better understanding of these areas may facilitate specific treatment approaches. Copyright © 2016 Elsevier B.V. All rights reserved.

Greater expression of TLR2, TLR4, and IL6 due to negative energy balance is associated with lower expression of HLA-DRA and HLA-A in bovine blood neutrophils after intramammary mastitis challenge with Streptococcus uberis

DEFF Research Database (Denmark)

Moyes, Kasey; Drackley, James K; Morin, Dawn E

2010-01-01

Our objectives were to compare gene expression profiles in blood polymorphonuclear cells (PMN) during a Streptococcus uberis intramammary challenge between lactating cows subjected to feed restriction to induce negative energy balance (NEB; n = 5) and cows fed ad libitum to maintain positive ener...

The not face: A grammaticalization of facial expressions of emotion.

Science.gov (United States)

Benitez-Quiroz, C Fabian; Wilbur, Ronnie B; Martinez, Aleix M

2016-05-01

Facial expressions of emotion are thought to have evolved from the development of facial muscles used in sensory regulation and later adapted to express moral judgment. Negative moral judgment includes the expressions of anger, disgust and contempt. Here, we study the hypothesis that these facial expressions of negative moral judgment have further evolved into a facial expression of negation regularly used as a grammatical marker in human language. Specifically, we show that people from different cultures expressing negation use the same facial muscles as those employed to express negative moral judgment. We then show that this nonverbal signal is used as a co-articulator in speech and that, in American Sign Language, it has been grammaticalized as a non-manual marker. Furthermore, this facial expression of negation exhibits the theta oscillation (3-8 Hz) universally seen in syllable and mouthing production in speech and signing. These results provide evidence for the hypothesis that some components of human language have evolved from facial expressions of emotion, and suggest an evolutionary route for the emergence of grammatical markers. Copyright © 2016 Elsevier B.V. All rights reserved.

Antibiotic-mediated selection of quorum-sensing-negative Staphylococcus aureus

DEFF Research Database (Denmark)

Paulander, Wilhelm Erik Axel; Varming, Anders Nissen; Bæk, Kristoffer Torbjørn

2012-01-01

of glycopeptide resistance greater than those of other strains. We show here that agr-negative strains have a fitness advantage over agr-positive strains in the presence of sublethal concentrations of some antibiotics and that the fitness defect of agr-positive cells is caused by antibiotic-mediated expression...... expression. We demonstrate that the presence of the agr locus imposes a fitness cost on S. aureus that is mediated by the expression of RNAIII. Further, we show that exposure to sublethal levels of the antibiotics ciprofloxacin, mupirocin, and rifampin, each targeting separate cellular functions, markedly...... increases the agr-mediated fitness cost by inducing the expression of RNAIII. Thus, the extensive use of antibiotics in hospitals may explain why agr-negative variants are frequently isolated from hospital-acquired S. aureus infections but rarely found among community-acquired S. aureus strains. Importantly...

Targeting Prolyl Peptidases in Triple-Negative Breast Cancer

Science.gov (United States)

2017-02-01

ABSTRACT Triple negative breast cancer (TNBC) is an aggressive sub-type with limited treatment options and poor prognosis. The most life -threatening... negative feedback loops within the pathway limit their effectiveness . For example, AKT inhibitors cause increased expression of IGF1R/ErbB3 and, as a...AWARD NUMBER: W81XWH-16-1-0025 TITLE: Targeting Prolyl Peptidases in Triple- Negative Breast Cancer PRINCIPAL INVESTIGATOR: Carl G. Maki, PhD

Monitoring of local CD8 β-expressing cell populations during Eimeria tenella infection of naïve and immune chickens

DEFF Research Database (Denmark)

Wattrang, Eva; Thebo, Per; Lunden, Anna

2016-01-01

The purpose of this study was to monitor abundance and activation of local CD8β-expressing T-cell populations during Eimeria tenella infections of naïve chickens and chickens immune by previous infections. Chickens were infected with E. tenella up to three times. Caecal T-cell receptor (TCR) γ...

Neuropharmacology of performance monitoring.

Science.gov (United States)

Jocham, Gerhard; Ullsperger, Markus

2009-01-01

Adaptive, goal-directed behavior requires that organisms evaluate their actions in terms of their outcomes. Neuroimaging studies show that unfavorable outcomes or situations with high level of conflict engage the posterior medial frontal cortex (pMFC). Recording of event-related potentials revealed that these situations are accompanied by a negative deflection, the so-called error-related negativity (ERN), which appears after an erroneous response or after negative feedback. Both activation of the pMFC and the ERN are thought to represent a signal that indicates the need for behavioral adjustment, and to recruit other brain regions that implement these adjustments. While many fMRI and EEG studies have shed light on the anatomical structures and the cognitive processes involved in performance monitoring, only very recently have researchers begun to investigate the underlying neurochemical mechanisms. Drawing on the putative involvement of dopamine (DA) neurons in coding a reward prediction error, an influential theory has ascribed a pivotal role to DA in performance monitoring. However, although important, DA is certainly not the only neuromodulator involved. Recent studies point to a role for serotonin, norepinephrine and GABA, but also for adenosine in performance monitoring. Here, we review the evidence for neurotransmitter effects on this function in humans. In this light, we critically discuss currently debated models of performance monitoring and potential alternatives.

Outcomes in Young Women With Breast Cancer of Triple-Negative Phenotype: The Prognostic Significance of CK19 Expression

International Nuclear Information System (INIS)

Parikh, Rahul R.; Yang Qifeng; Higgins, Susan A.; Haffty, Bruce G.

2008-01-01

Purpose: Basal-like carcinoma of the breast is associated with genetic instability and aggressive behavior. In this study, we evaluated the luminal cytokeratin marker CK-19 in young women with breast cancer treated with conservative surgery and radiation therapy (CS+RT). Methods: Primary tumor specimens from a cohort of 158 young premenopausal women (range, 25-49 years) treated with CS+RT with a median follow-up of 6.25 years were constructed into a tissue microarray. The array was stained for ER, PR, HER2, CK19, and p53. The molecular profiles were correlated with clinical-pathologic factors, overall, local, and distant relapse-free survival. The association between CK19, other co-variables, and outcome was assessed in a multivariate model. Results: Positive expression of ER, PR, HER-2/neu, CK19, and p53 were 33.1%, 34.5%, 10.0%, 79.5%, and 20.9%, respectively. With 20 local relapses and 38 distant metastases, the 10-year overall, breast relapse-free, and distant relapse-free survival were 79.65%, 87.29%, and 67.35%, respectively. Tumor stage and nodal status were associated with distant relapse-free and overall survival. In multivariate analysis, CK19 negativity was a predictor poor local (RR, 3.54; 95% CI, 1.87-7.65; p < 0.01) distant (RR, 1.44; 95% CI, 0.86-2.70; p = 0.17), and overall survival (RR, 1.89; 95% CI, 1.04-3.55; p = 0.03). Conclusions: Lack of CK19 expression identifies a subset of patients with a significantly higher risk of local relapse. Distant relapse and overall survival rates also correlated with CK19 negativity. Further evaluation of the prognostic significance of basal and luminal cytokeratins in young women with breast cancer is warranted

All in its proper time: monitoring the emergence of a memory bias for novel, arousing-negative words in individuals with high and low trait anxiety.

Science.gov (United States)

Eden, Annuschka Salima; Zwitserlood, Pienie; Keuper, Katharina; Junghöfer, Markus; Laeger, Inga; Zwanzger, Peter; Dobel, Christian

2014-01-01

The well-established memory bias for arousing-negative stimuli seems to be enhanced in high trait-anxious persons and persons suffering from anxiety disorders. We monitored the emergence and development of such a bias during and after learning, in high and low trait anxious participants. A word-learning paradigm was applied, consisting of spoken pseudowords paired either with arousing-negative or neutral pictures. Learning performance during training evidenced a short-lived advantage for arousing-negative associated words, which was not present at the end of training. Cued recall and valence ratings revealed a memory bias for pseudowords that had been paired with arousing-negative pictures, immediately after learning and two weeks later. This held even for items that were not explicitly remembered. High anxious individuals evidenced a stronger memory bias in the cued-recall test, and their ratings were also more negative overall compared to low anxious persons. Both effects were evident, even when explicit recall was controlled for. Regarding the memory bias in anxiety prone persons, explicit memory seems to play a more crucial role than implicit memory. The study stresses the need for several time points of bias measurement during the course of learning and retrieval, as well as the employment of different measures for learning success.

All in its proper time: monitoring the emergence of a memory bias for novel, arousing-negative words in individuals with high and low trait anxiety.

Directory of Open Access Journals (Sweden)

Annuschka Salima Eden

Full Text Available The well-established memory bias for arousing-negative stimuli seems to be enhanced in high trait-anxious persons and persons suffering from anxiety disorders. We monitored the emergence and development of such a bias during and after learning, in high and low trait anxious participants. A word-learning paradigm was applied, consisting of spoken pseudowords paired either with arousing-negative or neutral pictures. Learning performance during training evidenced a short-lived advantage for arousing-negative associated words, which was not present at the end of training. Cued recall and valence ratings revealed a memory bias for pseudowords that had been paired with arousing-negative pictures, immediately after learning and two weeks later. This held even for items that were not explicitly remembered. High anxious individuals evidenced a stronger memory bias in the cued-recall test, and their ratings were also more negative overall compared to low anxious persons. Both effects were evident, even when explicit recall was controlled for. Regarding the memory bias in anxiety prone persons, explicit memory seems to play a more crucial role than implicit memory. The study stresses the need for several time points of bias measurement during the course of learning and retrieval, as well as the employment of different measures for learning success.

A preliminary look at negative constructions in South African Sign ...

African Journals Online (AJOL)

How negation is expressed by means of manual and/or non-manual markers has been described in a wide range of sign languages. This work has suggested a split between sign languages requiring a manual negative element in negative clauses (manual dominant sign languages) and those where a non-manual marker ...

Expression levels of the receptor activator of NF-κB ligand and osteoprotegerin and the number of gram-negative bacteria in symptomatic and asymptomatic periapical lesions.

Science.gov (United States)

Carneiro, E; Parolin, A B; Wichnieski, C; Rosa, E A R; Silva Neto, U X; Westphalen, V P D; Fariniuk, L F; Johann, A C B R

2017-01-01

The study aimed to verify the potential correlation between the detected amount of gram-negative bacteria and the radiographic sizes of the lesions in patients with symptomatic and asymptomatic apical periodontitis. Furthermore, to evaluate whether the expression of receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) and the RANKL/OPG ratio are differentially regulated in both groups. Twenty patients with periapical lesions were divided into two groups: symptomatic (SYM) n=10 and asymptomatic (ASYM) n=10. After periapical surgery, the lesions were collected and processed for histological examination, and immunohistochemistry. The percentage of RANKL- and OPG-immunopositive areas relative to the total area of the microscopic field was calculated. For gram staining, the number of gram-negative cells per microscopic field was assessed. The radiographs of each patient were processed and measured. The Student's t-test and the Pearson correlation coefficient were performed. The SYM group showed a significantly higher number of gram-negative cells (p=0.007) when compared to the ASYM group. A higher number of gram-negative bacteria occurred more frequently in larger periapical lesions and the SYM group (p=0.03). The expression for RANKL and OPG and the RANKL/OPG ratio were not significantly different between the groups. There was a significant positive correlation between the number of bacteria and OPG levels in the SYM group (p=0.01). The number of bacteria seems to influence the symptoms and the radiographic size of a periapical lesion. Gram-negative bacteria may play an important role in OPG activity in the SYM group. Copyright © 2016 Elsevier Ltd. All rights reserved.

CTCF-KDM4A complex correlates with histone modifications that negatively regulate CHD5 gene expression in cancer cell lines

Science.gov (United States)

Guerra-Calderas, Lissania; González-Barrios, Rodrigo; Patiño, Carlos César; Alcaraz, Nicolás; Salgado-Albarrán, Marisol; de León, David Cantú; Hernández, Clementina Castro; Sánchez-Pérez, Yesennia; Maldonado-Martínez, Héctor Aquiles; De la Rosa-Velazquez, Inti A.; Vargas-Romero, Fernanda; Herrera, Luis A.; García-Carrancá, Alejandro; Soto-Reyes, Ernesto

2018-01-01

Histone demethylase KDM4A is involved in H3K9me3 and H3K36me3 demethylation, which are epigenetic modifications associated with gene silencing and RNA Polymerase II elongation, respectively. KDM4A is abnormally expressed in cancer, affecting the expression of multiple targets, such as the CHD5 gene. This enzyme localizes at the first intron of CHD5, and the dissociation of KDM4A increases gene expression. In vitro assays showed that KDM4A-mediated demethylation is enhanced in the presence of CTCF, suggesting that CTCF could increase its enzymatic activity in vivo, however the specific mechanism by which CTCF and KDM4A might be involved in the CHD5 gene repression is poorly understood. Here, we show that CTCF and KDM4A form a protein complex, which is recruited into the first intron of CHD5. This is related to a decrease in H3K36me3/2 histone marks and is associated with its transcriptional downregulation. Depletion of CTCF or KDM4A by siRNA, triggered the reactivation of CHD5 expression, suggesting that both proteins are involved in the negative regulation of this gene. Furthermore, the knockout of KDM4A restored the CHD5 expression and H3K36me3 and H3K36me2 histone marks. Such mechanism acts independently of CHD5 promoter DNA methylation. Our findings support a novel mechanism of epigenetic repression at the gene body that does not involve promoter silencing. PMID:29682202

Family emotional expressiveness and family structure

Directory of Open Access Journals (Sweden)

Čotar-Konrad Sonja

2016-01-01

Full Text Available The present paper scrutinizes the relationship between family emotional expressiveness (i.e., the tendency to express dominant and/or submissive positive and negative emotions and components of family structure as proposed in Olson’s Circumplex model (i.e., cohesion and flexibility, family communication, and satisfaction in families with adolescents. The study was conducted on a sample of 514 Slovenian adolescents, who filled out two questionnaires: the Slovenian version of Family Emotional Expressiveness - FEQ and FACES IV. The results revealed that all four basic dimensions of family functioning were significantly associated with higher/more frequent expressions of positive submissive emotions, as well as with lower/less frequent expressions of negative dominant emotions. Moreover, expressions of negative submissive emotions explained a small, but significant amount of variance in three out of four family functioning variables (satisfaction, flexibility, and communication. The importance of particular aspects of emotional expressiveness for family cohesion, flexibility, communication, and satisfaction is discussed, and the relevance of present findings for family counselling is outlined.

Positive Bioluminescence Imaging of MicroRNA Expression in Small Animal Models Using an Engineered Genetic-Switch Expression System, RILES.

Science.gov (United States)

Baril, Patrick; Pichon, Chantal

2016-01-01

MicroRNAs (miRNAs) are a class of small, noncoding RNAs which regulate gene expression by directing their target mRNA for degradation or translational repression. Since their discovery in the early 1990s, miRNAs have emerged as key components in the posttranscriptional regulation of gene networks, shaping many biological processes from development, morphogenesis, differentiation, proliferation and apoptosis. Although understanding of the molecular basis of miRNA biology is improving, methods to monitor the dynamic and the spatiotemporal aspects of miRNA expression under physiopathological conditions are required. However, monitoring of miRNAs is difficult due to their small size, low abundance, high degree of sequence similarity, and their dynamic expression pattern which is subjected to tight transcriptional and post-transcriptional controls. Recently, we developed a miRNA monitoring system called RILES, standing for RNAi-inducible expression system, which relies on an engineered regulatable expression system, to switch on the expression of the luciferase gene when the targeted miRNA is expressed in cells. We demonstrated that RILES is a specific, sensitive, and robust method to determine the fine-tuning of miRNA expression during the development of an experimental pathological process in mice. Because RILES offers the possibility for longitudinal studies on individual subjects, sharper insights into miRNA regulation can be generated, with applications in physiology, pathophysiology and development of RNAi-based therapies. This chapter describes methods and protocols to monitor the expression of myomiR-206, -1, and -133 in the tibialis anterior muscle of mice. These protocols can be used and adapted to monitor the expression of other miRNAs in other biological processes.

Analytical expression for position sensitivity of linear response beam position monitor having inter-electrode cross talk

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Kumar, Mukesh, E-mail: mukeshk@rrcat.gov.in [Beam Diagnostics Section, Indus Operations, Beam Dynamics & Diagnostics Division, Raja Ramanna Centre for Advanced Technology, Indore, 452013 MP (India); Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400 094 (India); Ojha, A.; Garg, A.D.; Puntambekar, T.A. [Beam Diagnostics Section, Indus Operations, Beam Dynamics & Diagnostics Division, Raja Ramanna Centre for Advanced Technology, Indore, 452013 MP (India); Senecha, V.K. [Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400 094 (India); Ion Source Lab., Proton Linac & Superconducting Cavities Division, Raja Ramanna Centre for Advanced Technology, Indore, 452013 MP (India)

2017-02-01

According to the quasi electrostatic model of linear response capacitive beam position monitor (BPM), the position sensitivity of the device depends only on the aperture of the device and it is independent of processing frequency and load impedance. In practice, however, due to the inter-electrode capacitive coupling (cross talk), the actual position sensitivity of the device decreases with increasing frequency and load impedance. We have taken into account the inter-electrode capacitance to derive and propose a new analytical expression for the position sensitivity as a function of frequency and load impedance. The sensitivity of a linear response shoe-box type BPM has been obtained through simulation using CST Studio Suite to verify and confirm the validity of the new analytical equation. Good agreement between the simulation results and the new analytical expression suggest that this method can be exploited for proper designing of BPM.

Quantitative monitoring of the Chlamydia trachomatis developmental cycle using GFP-expressing bacteria, microscopy and flow cytometry.

Directory of Open Access Journals (Sweden)

François Vromman

Full Text Available Chlamydiae are obligate intracellular bacteria. These pathogens develop inside host cells through a biphasic cycle alternating between two morphologically distinct forms, the infectious elementary body and the replicative reticulate body. Recently, C. trachomatis strains stably expressing fluorescent proteins were obtained. The fluorochromes are expressed during the intracellular growth of the microbe, allowing bacterial visualization by fluorescence microscopy. Whether they are also present in the infectious form, the elementary body, to a detectable level has not been studied. Here, we show that a C. trachomatis strain transformed with a plasmid expressing the green fluorescent protein (GFP accumulates sufficient quantities of the probe in elementary bodies for detection by microscopy and flow cytometry. Adhesion of single bacteria was detected. The precise kinetics of bacterial entry were determined by microscopy using automated procedures. We show that during the intracellular replication phase, GFP is a convenient read-out for bacterial growth with several advantages over current methods. In particular, infection rates within a non-homogenous cell population are easily quantified. Finally, in spite of their small size, individual elementary bodies are detected by flow cytometers, allowing for direct enumeration of a bacterial preparation. In conclusion, GFP-expressing chlamydiae are suitable to monitor, in a quantitative manner, progression throughout the developmental cycle. This will facilitate the identification of the developmental steps targeted by anti-chlamydial drugs or host factors.

Preservation Copying Endangered Historic Negative Collections

DEFF Research Database (Denmark)

Kejser, Ulla Bøgvad

2008-01-01

This article discusses preservation copying of unstable B&W nitrate and acetate still photographic negatives. It focuses on evaluating two different strategies for preserving the copies from a point of view of quality and cost-effectiveness. The evaluated strategies are preservation of the master...... by describing essential characteristics of negatives, which must be passed on to the copies, and the required metadata and technical imaging specifications. Next the paper discusses strategies for preservation and makes an analysis with the LIFE2 Costing Model. The paper concludes that the most beneficial...... and cost-effective preservation solution for large format negatives is to keep the preservation copies as digital files. However, it also acknowledges that it is important to revisit such strategies regularly to monitor changes in user expectations, technologies and costs....

miR-375-3p negatively regulates osteogenesis by targeting and decreasing the expression levels of LRP5 and β-catenin.

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Tianhao Sun

Full Text Available Wnt signaling pathways are essential for bone formation. Previous studies showed that Wnt signaling pathways were regulated by miR-375. Thus, we aim to explore whether miR-375 could affect osteogenesis. In the present study, we investigated the roles of miR-375 and its downstream targets. Firstly, we revealed that miR-375-3p negatively modulated osteogenesis by suppressing positive regulators of osteogenesis and promoting negative regulators of osteogenesis. In addition, the results of TUNEL cell apoptosis assay showed that miR-375-3p induced MC3T3-E1 cell apoptosis. Secondly, miR-375-3p targeted low-density lipoprotein receptor-related protein 5 (LRP5, a co-receptor of the Wnt signaling pathways, and β-catenin as determined by luciferase activity assay, and it decreased the expression levels of LRP5 and β-catenin. Thirdly, the decline of protein levels of β-catenin was determined by immunocytochemistry and immunofluorescence. Finally, silence of LRP5 in osteoblast precursor cells resulted in diminished cell viability and cell proliferation as detected by WST-1-based colorimetric assay. Additionally, all the parameters including the relative bone volume from μCT measurement suggested that LRP5 knockout in mice resulted in a looser and worse-connected trabeculae. The mRNA levels of important negative modulators relating to osteogenesis increased after the functions of LRP5 were blocked in mice. Last but not least, the expression levels of LRP5 increased during the osteogenesis of MC3T3-E1, while the levels of β-catenin decreased in bone tissues from osteoporotic patients with vertebral compression fractures. In conclusion, we revealed miR-375-3p negatively regulated osteogenesis by targeting LRP5 and β-catenin. In addition, loss of functions of LRP5 damaged bone formation in vivo. Clinically, miR-375-3p and its targets might be used as diagnostic biomarkers for osteoporosis and might be also as novel therapeutic agents in osteoporosis

The influence of positive vs. negative affect on multitasking.

Science.gov (United States)

Morgan, Brent; D'Mello, Sidney K

2016-10-01

Considerable research has investigated how affect influences performance on a single task; however, little is known about the role of affect in complex multitasking environments. In this paper, 178 participants multitasked in a synthetic work environment (SYNWORK) consisting of memory, visual monitoring, auditory monitoring, and math tasks. Participants multitasked for a 3-min baseline phase (MT1), following which they were randomly assigned to watch one of three affect-induction videos: positive, neutral, or negative. Participants then resumed multitasking for two additional critical phases (MT2, MT3; 3min each). In MT2, performance of the positive and neutral conditions was statistically equivalent and higher than the negative condition. In MT3, the positive condition performed better than the negative condition, with the neutral condition not significantly different from the other two. The differences in overall multitasking scores were largely driven by errors in the Math task (the most cognitively demanding task) in MT2 and the Memory task in MT3. These findings have implications for how positive and negative affective states influence processing in a cognitively demanding multitasking environment. Copyright © 2016 Elsevier B.V. All rights reserved.

Surface expression and limited proteolysis of ADAM10 are increased by a dominant negative inhibitor of dynamin

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Slack Barbara E

2011-05-01

Full Text Available Abstract Background The amyloid precursor protein (APP is cleaved by β- and γ-secretases to generate toxic amyloid β (Aβ peptides. Alternatively, α-secretases cleave APP within the Aβ domain, precluding Aβ formation and releasing the soluble ectodomain, sAPPα. We previously showed that inhibition of the GTPase dynamin reduced APP internalization and increased release of sAPPα, apparently by prolonging the interaction between APP and α-secretases at the plasma membrane. This was accompanied by a reduction in Aβ generation. In the present study, we investigated whether surface expression of the α-secretase ADAM (a disintegrin and metalloprotease10 is also regulated by dynamin-dependent endocytosis. Results Transfection of human embryonic kidney (HEK cells stably expressing M3 muscarinic receptors with a dominant negative dynamin I mutant (dyn I K44A, increased surface expression of both immature, and mature, catalytically active forms of co-expressed ADAM10. Surface levels of ADAM10 were unaffected by activation of protein kinase C (PKC or M3 receptors, indicating that receptor-coupled shedding of the ADAM substrate APP is unlikely to be mediated by inhibition of ADAM10 endocytosis in this cell line. Dyn I K44A strongly increased the formation of a C-terminal fragment of ADAM10, consistent with earlier reports that the ADAM10 ectodomain is itself a target for sheddases. The abundance of this fragment was increased in the presence of a γ-secretase inhibitor, but was not affected by M3 receptor activation. The dynamin mutant did not affect the distribution of ADAM10 and its C-terminal fragment between raft and non-raft membrane compartments. Conclusions Surface expression and limited proteolysis of ADAM10 are regulated by dynamin-dependent endocytosis, but are unaffected by activation of signaling pathways that upregulate shedding of ADAM substrates such as APP. Modulation of ADAM10 internalization could affect cellular behavior in two

Differences in expression of the cancer stem cell marker aldehyde dehydrogenase 1 among estrogen receptor-positive/human epidermal growth factor receptor type 2-negative breast cancer cases with early, late, and no recurrence.

Science.gov (United States)

Miyoshi, Yuichiro; Shien, Tadahiko; Ogiya, Akiko; Ishida, Naoko; Yamazaki, Kieko; Horii, Rie; Horimoto, Yoshiya; Masuda, Norikazu; Yasojima, Hiroyuki; Inao, Touko; Osako, Tomofumi; Takahashi, Masato; Tomioka, Nobumoto; Endo, Yumi; Hosoda, Mitsuchika; Doihara, Hiroyoshi; Miyoshi, Shinichiro; Yamashita, Hiroko

2016-07-02

The significance of the expression of aldehyde dehydrogenase 1 (ALDH1), a cancer stem cell marker, for predicting the recurrence of estrogen receptor (ER)-positive/human epidermal growth factor receptor type 2 (HER2)-negative breast cancer is still poorly understood. The value of ALDH1 in predicting the time of recurrence remains unknown. In total, 184 patients with early distant recurrence, 134 patients with late distant recurrence, and 321 control patients without recurrence for more than 10 years after starting initial treatment for ER-positive/HER2-negative breast cancer, registered in 9 institutions, were analyzed. We assessed relationships between ALDH1 and other clinicopathological features, and ALDH1 expression was compared among the three groups. The relationship between ALDH1 expression and overall survival after recurrence was also evaluated in each group. The rates of ALDH1 expression positivity (more than 1 %) in the early, late, and no recurrence groups were 18.4 %, 13.4 %, and 8.4 %, respectively. ALDH1 expression correlated significantly with lymph node metastases (p = 0.048) and the Ki-67 labeling index (p factor independently predicting overall survival after the detection of recurrence (adjusted OR 1.451, 95 % CI 0.985-2.085, p = 0.059). Among patients with ER-positive/HER2-negative breast cancer, ALDH1 expression was more common in those with early recurrence, and this expression was found to be associated with a more aggressive breast cancer phenotype than that in the patients without recurrence. Further study is needed to clarify the prognostic significance of the heterogeneity of cancer stem cells and to confirm their role in resistance to chemotherapy.

High ALK mRNA expression has a negative prognostic significance in rhabdomyosarcoma

OpenAIRE

Bonvini, P; Zin, A; Alaggio, R; Pawel, B; Bisogno, G; Rosolen, A

2013-01-01

Background: Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase aberrantly expressed in cancer, but its clinical and functional importance remain controversial. Mutation or amplification of ALK, as well as its expression levels assessed by conventional immunohistochemistry methods, has been linked to prognosis in cancer, although with potential bias because of the semi-quantitative approaches. Herein, we measured ALK mRNA expression in rhabdomyosarcoma (RMS) and determined its clin...

Emotion recognition in borderline personality disorder: effects of emotional information on negative bias.

Science.gov (United States)

Fenske, Sabrina; Lis, Stefanie; Liebke, Lisa; Niedtfeld, Inga; Kirsch, Peter; Mier, Daniela

2015-01-01

Borderline Personality Disorder (BPD) is characterized by severe deficits in social interactions, which might be linked to deficits in emotion recognition. Research on emotion recognition abilities in BPD revealed heterogeneous results, ranging from deficits to heightened sensitivity. The most stable findings point to an impairment in the evaluation of neutral facial expressions as neutral, as well as to a negative bias in emotion recognition; that is the tendency to attribute negative emotions to neutral expressions, or in a broader sense to report a more negative emotion category than depicted. However, it remains unclear which contextual factors influence the occurrence of this negative bias. Previous studies suggest that priming by preceding emotional information and also constrained processing time might augment the emotion recognition deficit in BPD. To test these assumptions, 32 female BPD patients and 31 healthy females, matched for age and education, participated in an emotion recognition study, in which every facial expression was preceded by either a positive, neutral or negative scene. Furthermore, time constraints for processing were varied by presenting the facial expressions with short (100 ms) or long duration (up to 3000 ms) in two separate blocks. BPD patients showed a significant deficit in emotion recognition for neutral and positive facial expression, associated with a significant negative bias. In BPD patients, this emotion recognition deficit was differentially affected by preceding emotional information and time constraints, with a greater influence of emotional information during long face presentations and a greater influence of neutral information during short face presentations. Our results are in line with previous findings supporting the existence of a negative bias in emotion recognition in BPD patients, and provide further insights into biased social perceptions in BPD patients.

AUTOCOUNTER, an ImageJ JavaScript to analyze LC3B-GFP expression dynamics in autophagy-induced astrocytoma cells.

Science.gov (United States)

Fassina, L; Magenes, G; Inzaghi, A; Palumbo, S; Allavena, G; Miracco, C; Pirtoli, L; Biggiogera, M; Comincini, S

2012-10-11

An ImageJ JavaScript, AUTOCOUNTER, was specifically developed to monitor and measure LC3B-GFP expression in living human astrocytoma cells, namely T98G and U373-MG. Discrete intracellular GFP fluorescent spots derived from transduction of a Baculovirus replication-defective vector (BacMam LC3B-GFP), followed by microscope examinations at different times. After viral transgene expression, autophagy was induced by Rapamycin administration and assayed in ph-p70S6K/p70S6K and LC3B immunoblotting expression as well as by electron microscopy examinations. A mutated transgene, defective in LC3B lipidation, was employed as a negative control to further exclude fluorescent dots derived from protein intracellular aggregation. The ImageJ JavaScript was then employed to evaluate and score the dynamics changes of the number and area of LC3B-GFP puncta per cell in time course assays and in complex microscope examinations. In conclusion, AUTOCOUNTER enabled to quantify LC3B-GFP expression and to monitor dynamics changes in number and shapes of autophagosomal-like vesicles: it might therefore represent a suitable algorithmic tool for in vitro autophagy modulation studies.

Factor structure of the Brief Negative Symptom Scale.

Science.gov (United States)

Strauss, Gregory P; Hong, L Elliot; Gold, James M; Buchanan, Robert W; McMahon, Robert P; Keller, William R; Fischer, Bernard A; Catalano, Lauren T; Culbreth, Adam J; Carpenter, William T; Kirkpatrick, Brian

2012-12-01

The current study examined the factor structure of the Brief Negative Symptom Scale (BNSS), a next-generation negative symptom rating instrument developed in response to the NIMH-sponsored Consensus Development Conference on Negative Symptoms. Participants included 146 individuals with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder. Principal axis factoring indicated two distinct factors explaining 68.7% of the variance. Similar to previous findings, the factors reflected motivation and pleasure and emotional expressivity. These findings provide further support for the construct validity of the BNSS, and for the existence of these two negative symptom factors. Copyright © 2012 Elsevier B.V. All rights reserved.

The Relationship Between Attachment Styles, Self-Monitoring and Cybercrime in Social Network Users.

Science.gov (United States)

Yaghoobi, Abolghasem; Mohammadzade, Serwa; Chegini, Ali Asghar; Yarmohammadi Vasel, Mosaeib; Zoghi Paidar, Mohammad Reza

2016-09-01

The anonymity in the cyberspace environment, as well as the rapid advent of and improvements to online activities has increased cybercrime. The aim of this paper was to survey the relationship between attachment styles, self-monitoring and cybercrime in social network users. The Collins and Read Adult Attachment Scale, and the Snyder self-monitoring and cybercrime scales were sent to 500 social network users. Of these, 203 users (103 men and 100 women) filled out the questionnaires. The results showed that women achieved higher scores in self-monitoring and the anxious attachment style, and men achieved higher scores in cybercrime and the anxious attachment style. There was a negative correlation between self-monitoring and cybercrime, and the anxious attachment style had a positive correlation with cybercrime and a negative correlation with self-monitoring. The secure attachment style had a positive correlation with self-monitoring and a negative correlation with cybercrime. The dependent attachment style had a positive correlation with self-monitoring and a negative correlation with cybercrime. All correlations were significant. Attachment styles have significant relationships with both self-monitoring and cybercrime. Self-monitoring and attachment styles are significant predictors of cybercrimes.

Monitoring Costs and Multinational-Bank Lending

OpenAIRE

Ralph de Haas

2006-01-01

We use a two-country model to examine how endogenous changes in monitoring intensity and exogenous changes in monitoring efficiency affect multinational-bank lending. First, an endogenous decline in monitoring intensity limits the amount of deposits that banks can attract. This lowers bank lending. Shocks that reduce bank capital relative to firm capital therefore have a stronger negative effect on bank lending compared to a model with exogenous monitoring intensity. Second, international dif...

Nestin expression in neuroepithelial tumors.

Science.gov (United States)

Schiffer, Davide; Manazza, Andrea; Tamagno, Ilaria

2006-05-29

Nestin is a marker of early stages of neurocytogenesis. It has been studied in 50 neuroepithelial tumors, mostly gliomas of different malignancy grades, by immunohistochemistry, immunofluorescence, immunoblotting, and confocal microscopy and compared with GFAP and Vimentin. As an early marker of differentiation, Nestin is almost not expressed in diffuse astrocytomas, variably expressed in anaplastic astrocytomas and strongly and irregularly expressed in glioblastomas. Negative in oligodendrogliomas, it stains ependymomas and shows a gradient of expression in pilocytic astrocytomas. In glioblastomas, Nestin distribution does not completely correspond to that of GFAP and Vimentin with which its expression varies in tumor cells in a complementary way, as confirmed by confocal microscopy. Tumor cells can thus either derive from or differentiate toward the neurocytogenetic stages. Hypothetically, they could be put in relation with radial glia where during embriogenesis the three antigens are successively expressed. Completely negative cells of invasive or recurrent glioblastomas may represent malignant selected clones after accumulation of mutations or early stem cells not expressing antigens.

Liver X Receptor (LXR) activation negatively regulates visfatin expression in macrophages

Energy Technology Data Exchange (ETDEWEB)

Mayi, Therese Hervee; Rigamonti, Elena [Univ Lille Nord de France, F-59000 Lille (France); INSERM UR1011, F-59000 Lille (France); UDSL, F-59000 Lille (France); Institut Pasteur de Lille, F-59019 Lille (France); Pattou, Francois [Univ Lille Nord de France, F-59000 Lille (France); Department of Endocrine Surgery, University Hospital, Lille (France); U859 Biotherapies for Diabetes, INSERM, Lille (France); Staels, Bart, E-mail: bart.staels@pasteur-lille.fr [Univ Lille Nord de France, F-59000 Lille (France); INSERM UR1011, F-59000 Lille (France); UDSL, F-59000 Lille (France); Institut Pasteur de Lille, F-59019 Lille (France); Chinetti-Gbaguidi, Giulia [Univ Lille Nord de France, F-59000 Lille (France); INSERM UR1011, F-59000 Lille (France); UDSL, F-59000 Lille (France); Institut Pasteur de Lille, F-59019 Lille (France)

2011-01-07

Research highlights: {yields} Synthetic LXR ligands decreased visfatin expression in human macrophages. {yields} LXR activation leads to a modest and transient decrease of NAD{sup +} concentration. {yields} LXR activation decreased PPAR{gamma}-induced visfatin in human macrophages. -- Abstract: Adipose tissue macrophages (ATM) are the major source of visfatin, a visceral fat adipokine upregulated during obesity. Also known to play a role in B cell differentiation (pre-B cell colony-enhancing factor (PBEF)) and NAD biosynthesis (nicotinamide phosphoribosyl transferase (NAMPT)), visfatin has been suggested to play a role in inflammation. Liver X Receptor (LXR) and Peroxisome Proliferator-Activated Receptor (PPAR){gamma} are nuclear receptors expressed in macrophages controlling the inflammatory response. Recently, we reported visfatin as a PPAR{gamma} target gene in human macrophages. In this study, we examined whether LXR regulates macrophage visfatin expression. Synthetic LXR ligands decreased visfatin gene expression in a LXR-dependent manner in human and murine macrophages. The decrease of visfatin mRNA was paralleled by a decrease of protein secretion. Consequently, a modest and transient decrease of NAD{sup +} concentration was observed. Interestingly, LXR activation decreased the PPAR{gamma}-induced visfatin gene and protein secretion in human macrophages. Our results identify visfatin as a gene oppositely regulated by the LXR and PPAR{gamma} pathways in human macrophages.

Plasma diagnostic tools for optimizing negative hydrogen ion sources

International Nuclear Information System (INIS)

Fantz, U.; Falter, H.D.; Franzen, P.; Speth, E.; Hemsworth, R.; Boilson, D.; Krylov, A.

2006-01-01

The powerful diagnostic tool of optical emission spectroscopy is used to measure the plasma parameters in negative hydrogen ion sources based on the surface mechanism. Results for electron temperature, electron density, atomic-to-molecular hydrogen density ratio, and gas temperature are presented for two types of sources, a rf source and an arc source, which are currently under development for a neutral beam heating system of ITER. The amount of cesium in the plasma volume is obtained from cesium radiation: the Cs neutral density is five to ten orders of magnitude lower than the hydrogen density and the Cs ion density is two to three orders of magnitude lower than the electron density in front of the grid. It is shown that monitoring of cesium lines is very useful for monitoring the cesium balance in the source. From a line-ratio method negative ion densities are determined. In a well-conditioned source the negative ion density is of the same order of magnitude as the electron density and correlates with extracted current densities

The developmental origins of cognitive vulnerability to depression: temperament, parenting, and negative life events in childhood as contributors to negative cognitive style.

Science.gov (United States)

Mezulis, Amy H; Hyde, Janet Shibley; Abramson, Lyn Y

2006-11-01

Cognitive models of depression have been well supported with adults, but the developmental origins of cognitive vulnerability are not well understood. The authors hypothesized that temperament, parenting, and negative life events in childhood would contribute to the development of cognitive style, with withdrawal negativity and negative parental feedback moderating the effects of negative life events to predict more depressogenic cognitive styles. These constructs were assessed in 289 children and their parents followed longitudinally from infancy to 5th grade; a subsample (n = 120) also participated in a behavioral task in which maternal feedback to child failure was observed. Results indicated that greater withdrawal negativity in interaction with negative life events was associated with more negative cognitive styles. Self-reported maternal anger expression and observed negative maternal feedback to child's failure significantly interacted with child's negative events to predict greater cognitive vulnerability. There was little evidence of paternal parenting predicting child negative cognitive style.

Antimicrobial susceptibility profiles of gram-negative bacteria causing infections collected across India during 2014–2016: Study for monitoring antimicrobial resistance trend report

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Balaji Veeraraghavan

2018-01-01

Full Text Available Background: The emergence of antibiotic resistance among bacterial pathogens in the hospital and community has increased the concern to the health-care providers due to the limited treatment options. Surveillance of antimicrobial resistance (AMR in frequently isolated bacterial pathogens causing severe infections is of great importance. The data generated will be useful for the clinicians to decide empiric therapy on the local epidemiological resistance profile of the antimicrobial agents. This study aims to monitor the distribution of bacterial pathogen and their susceptibility pattern to the commonly used antimicrobial agents. Materials and Methods: This study includes Gram-negative bacilli collected from intra-abdominal, urinary tract and respiratory tract infections during 2014–2016. Isolates were collected from seven hospitals across India. All the study isolates were characterised up to species level, and minimum inhibitory concentration was determined for a wide range of antimicrobials included in the study panel. The test results were interpreted as per standard Clinical Laboratory Standards Institute guidelines. Results: A total of 2731 isolates of gram-negative bacteria were tested during study period. The most frequently isolated pathogens were 44% of Escherichia coli (n = 1205 followed by 25% of Klebsiella pneumoniae (n = 676 and 11% of Pseudomonas aeruginosa (n = 308. Among the antimicrobials tested, carbapenems were the most active, followed by amikacin and piperacillin/tazobactam. The rate of extended-spectrum beta-lactamase (ESBL-positive isolates were ranged from 66%–77% in E. coli to 61%–72% in K. pneumoniae, respectively. Overall, colistin retains its activity in > 90% of the isolates tested and appear promising. Conclusion: Increasing rates of ESBL producers have been noted, which is alarming. Further, carbapenem resistance was also gradually increasing, which needs much attention. Overall, this study data show that

Three gene expression vector sets for concurrently expressing multiple genes in Saccharomyces cerevisiae.

Science.gov (United States)

Ishii, Jun; Kondo, Takashi; Makino, Harumi; Ogura, Akira; Matsuda, Fumio; Kondo, Akihiko

2014-05-01

Yeast has the potential to be used in bulk-scale fermentative production of fuels and chemicals due to its tolerance for low pH and robustness for autolysis. However, expression of multiple external genes in one host yeast strain is considerably labor-intensive due to the lack of polycistronic transcription. To promote the metabolic engineering of yeast, we generated systematic and convenient genetic engineering tools to express multiple genes in Saccharomyces cerevisiae. We constructed a series of multi-copy and integration vector sets for concurrently expressing two or three genes in S. cerevisiae by embedding three classical promoters. The comparative expression capabilities of the constructed vectors were monitored with green fluorescent protein, and the concurrent expression of genes was monitored with three different fluorescent proteins. Our multiple gene expression tool will be helpful to the advanced construction of genetically engineered yeast strains in a variety of research fields other than metabolic engineering. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

HER-2 positive and p53 negative breast cancers are associated with poor prognosis.

LENUS (Irish Health Repository)

2011-06-01

p53 and HER-2 coexpression in breast cancer has been controversial. These markers were tested using immunohistochemistry and HercepTest. HER-2 expression is related to reduced breast cancer survival (p = .02) . p53 expression relates to HER-2 expression (p = .029). Coexpression between p53 and HER-2 has no relation to prognosis. On univariate and multivariate analysis, combination of HER-2 positive and p53 negative expression was associated with a poor prognosis (p = .018 and p = .027, respectively), while the combination of HER-2 negative and p53 positive expression was associated with a favorable prognosis (p = .022 and p = .010, respectively). Therefore the expression of these markers should be considered collectively.

HER-2 positive and p53 negative breast cancers are associated with poor prognosis.

LENUS (Irish Health Repository)

2012-02-01

p53 and HER-2 coexpression in breast cancer has been controversial. These markers were tested using immunohistochemistry and HercepTest. HER-2 expression is related to reduced breast cancer survival (p = .02) . p53 expression relates to HER-2 expression (p = .029). Coexpression between p53 and HER-2 has no relation to prognosis. On univariate and multivariate analysis, combination of HER-2 positive and p53 negative expression was associated with a poor prognosis (p = .018 and p = .027, respectively), while the combination of HER-2 negative and p53 positive expression was associated with a favorable prognosis (p = .022 and p = .010, respectively). Therefore the expression of these markers should be considered collectively.

Androgen receptor status is a prognostic marker in non-basal triple negative breast cancers and determines novel therapeutic options.

Directory of Open Access Journals (Sweden)

Pierluigi Gasparini

Full Text Available Triple negative breast cancers are a heterogeneous group of tumors characterized by poor patient survival and lack of targeted therapeutics. Androgen receptor has been associated with triple negative breast cancer pathogenesis, but its role in the different subtypes has not been clearly defined. We examined androgen receptor protein expression by immunohistochemical analysis in 678 breast cancers, including 396 triple negative cancers. Fifty matched lymph node metastases were also examined. Association of expression status with clinical (race, survival and pathological (basal, non-basal subtype, stage, grade features was also evaluated. In 160 triple negative breast cancers, mRNA microarray expression profiling was performed, and differences according to androgen receptor status were analyzed. In triple negative cancers the percentage of androgen receptor positive cases was lower (24.8% vs 81.6% of non-triple negative cases, especially in African American women (16.7% vs 25.5% of cancers of white women. No significant difference in androgen receptor expression was observed in primary tumors vs matched metastatic lesions. Positive androgen receptor immunoreactivity was inversely correlated with tumor grade (p<0.01 and associated with better overall patient survival (p = 0.032 in the non-basal triple negative cancer group. In the microarray study, expression of three genes (HER4, TNFSF10, CDK6 showed significant deregulation in association with androgen receptor status; eg CDK6, a novel therapeutic target in triple negative cancers, showed significantly higher expression level in androgen receptor negative cases (p<0.01. These findings confirm the prognostic impact of androgen receptor expression in non-basal triple negative breast cancers, and suggest targeting of new androgen receptor-related molecular pathways in patients with these cancers.

Expression of MLH1 and MSH2 in urothelial carcinoma of the renal pelvis.

Science.gov (United States)

Ehsani, Laleh; Osunkoya, Adeboye O

2014-09-01

In this study, we investigated microsatellite instability in urothelial carcinoma of the renal pelvis by lack of immunohistochemical staining for MLH1 and MSH2. The study included 44 cases of urothelial carcinoma of the renal pelvis obtained from radical nephroureterectomy specimens at our institution. We evaluated the loss of nuclear immunohistochemical staining of MLH1 and MSH2. Eight of 44 (18 %) patients had negative MLH1 expression and 25/44 (57 %) patients had negative MSH2 expression. Six of 8 (75 %) patients with negative MLH1 expression were male and 2/8 (25 %) patients were female. Nineteen of 25 (75 %) patients with negative MSH2 expression were male, and 6/25 (24 %) patients were female. Seven of 8 (88 %) cases with negative MLH1 expression were high-grade urothelial carcinoma, and 21/25 (84 %) cases with negative MSH2 expression were high-grade urothelial carcinoma. Twenty-one of 44 (48 %) cases had an inverted growth pattern, of which 3/21 (14 %) cases had negative MLH1 expression and 14/21 (67 %) cases had negative MSH2 expression. Our study showed that microsatellite instability based on negative expression of MLH1 and MSH2 was more common in male patients with high-grade urothelial carcinoma. There is a strong correlation between inverted growth pattern and negative MSH2 expression. Microsatellite instability testing should be performed in patients with upper urinary tract carcinoma and may have prognostic value.

Temporal dynamics of conflict monitoring and the effects of one or two conflict sources on error-(related) negativity.

Science.gov (United States)

Armbrecht, Anne-Simone; Wöhrmann, Anne; Gibbons, Henning; Stahl, Jutta

2010-09-01

The present electrophysiological study investigated the temporal development of response conflict and the effects of diverging conflict sources on error(-related) negativity (Ne). Eighteen participants performed a combined stop-signal flanker task, which was comprised of two different conflict sources: a left-right and a go-stop response conflict. It is assumed that the Ne reflects the activity of a conflict monitoring system and thus increases according to (i) the number of conflict sources and (ii) the temporal development of the conflict activity. No increase of the Ne amplitude after double errors (comprising two conflict sources) as compared to hand- and stop-errors (comprising one conflict source) was found, whereas a higher Ne amplitude was observed after a delayed stop-signal onset. The results suggest that the Ne is not sensitive to an increase in the number of conflict sources, but to the temporal dynamics of a go-stop response conflict. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Schizophrenia and smoking: impact on negative symptoms

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Miriam Saliba

2017-06-01

Full Text Available Introduction: it has been hypothesized that individuals with schizophrenia use nicotine to reduce negative symptoms and improve cognitive function. There is an inconsistency in the literature suggesting that nicotine could help decrease negative symptoms in schizophrenic patients. Objective: to investigate the effects of nicotine on the expression of the negative symptoms in smokers and non-smokers with schizophrenia. Methods: a cross sectional study, conducted between April and August 2016, 100 inpatients with schizophrenia (54 smokers and 46 non-smokers diagnosed according to DSM-V, at Psychiatric Hospital of the Cross Lebanon, were compared to changes in clinical parameters using CDSS, PANSS, and nicotine dependence using FTND. The Student’s t-test was used to compare between 2 groups, while the ANOVA test was used to compare between 3 or more groups. For categorical variables, the chi-2 test was used. Results: the mean age was 47.16 years (SD = 7.14 for smokers compared to 47.02 years (SD = 7.92 for non-smokers. 64.8% of smokers were males versus 45.7% of non-smokers. Smoking (high nicotine dependence significantly decreases the PANSS negative symptoms score between the 2 groups (p .05 for both variables. Discussion and conclusion: this study is the first to investigate the relationship between the expression of negative symptoms in individuals with schizophrenia and smoking in Lebanon. Cigarette smoking rates remain remarkably high in patients with schizophrenia. Smoking is a complex process which involves psychopathological, biochemical and neuropharmacological aspects among schizophrenic patients. Further studies are needed to acknowledge these findings and the reasons behind it.

Her-2/neu expression in node-negative breast cancer: direct tissue quantitation by computerized image analysis and association of overexpression with increased risk of recurrent disease.

Science.gov (United States)

Press, M F; Pike, M C; Chazin, V R; Hung, G; Udove, J A; Markowicz, M; Danyluk, J; Godolphin, W; Sliwkowski, M; Akita, R

1993-10-15

The HER-2/neu proto-oncogene (also known as c-erb B-2) is homologous with, but distinct from, the epidermal growth factor receptor. Amplification of this gene in node-positive breast cancers has been shown to correlate with both earlier relapse and shorter overall survival. In node-negative breast cancer patients, the subgroup for which accurate prognostic data could make a significant contribution to treatment decisions, the prognostic utility of HER-2/neu amplification and/or overexpression has been controversial. The purpose of this report is to address the issues surrounding this controversy and to evaluate the prognostic utility of overexpression in a carefully followed group of patients using appropriately characterized reagents and methods. In this report we present data from a study of HER-2/neu expression designed specifically to test whether or not overexpression is associated with an increased risk of recurrence in node-negative breast cancers. From a cohort of 704 women with node-negative breast cancer who experienced recurrent disease (relapsed cases) 105 were matched with 105 women with no recurrence (disease-free controls) after the equivalent follow-up period. Immunohistochemistry was used to assess HER-2/neu expression in archival tissue blocks from both relapsed cases and their matched disease-free controls. Importantly, a series of molecularly characterized breast cancer specimens were used to confirm that the antibody used was of sufficient sensitivity and specificity to identify those cancers overexpressing the HER-2/neu protein in this formalin-fixed, paraffin-embedded tissue cohort. In addition, a quantitative approach was developed to more accurately assess the amount of HER-2/neu protein identified by immunostaining tumor tissue. This was done using a purified HER-2/neu protein synthesized in a bacterial expression vector and protein lysates derived from a series of cell lines, engineered to express a defined range of HER-2/neu oncoprotein

Effect of Negative Pressure Wound Therapy on Cellular Fibronectin and Transforming Growth Factor-β1 Expression in Diabetic Foot Wounds.

Science.gov (United States)

Yang, Shao Ling; Zhu, Lv Yun; Han, Rui; Sun, Lei Lei; Dou, Jing Tao

2017-08-01

Chronic diabetic foot wounds are a leading cause of amputation, morbidity, and hospitalization for patients with diabetes. Negative-pressure wound therapy (NPWT) can putatively facilitate wound healing, but the underlying mechanisms remain unclear. Cellular fibronectin (cFN) and transforming growth factor-β1 (TGF-β1) play an important role in wound healing. This prospective randomized controlled trial evaluated the effects of NPWT on the production of cFN and the expression of TGF-β1 in diabetic foot wounds of patients. From January 2012 to January 2015, 40 patients with diabetic foot wounds were randomly and equally apportioned to receive either NPWT or advanced moist wound therapy (control) for 7 days. Granulation tissue was harvested before and after treatment. Immunohistochemistry and Western blot were performed to evaluate protein levels of cFN and TGF-β1, and real-time polymerase chain reaction (PCR) to measure corresponding mRNA expressions. NPWT facilitated the expression of cFN and TGF-β1 in diabetic foot wounds. Immunohistochemical analysis revealed higher levels of cFN and TGF-β1 in the NPWT group than in the control group. Western blot and real-time PCR analysis further showed that protein and mRNA levels of cFN or TGF-β1 were higher in the NPWT group than that in the control group ( P diabetic foot ulcers. Level I, randomized controlled study.

WRKY2/34–VQ20 Modules in Arabidopsis thaliana Negatively Regulate Expression of a Trio of Related MYB Transcription Factors During Pollen Development

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Rihua Lei

2018-03-01

Full Text Available Male gametogenesis in plants is tightly controlled and involves the complex and precise regulation of transcriptional reprogramming. Interactions between WRKY proteins and VQ motif-containing proteins are required to control these complicated transcriptional networks. However, our understanding of the mechanisms by which these complexes affect downstream gene expression is quite limited. In this study, we found that WRKY2 and WKRY34 repress MYB97, MYB101, and MYB120 expression during male gametogenesis. MYB expression was up-regulated in the wrky2-1 wrky34-1 vq20-1 triple mutant during male gametogenesis. The expression levels of six potential targets of the three MYBs increased the most in the wrky2-1 wrky34-1 vq20-1 triple mutant, followed by the wrky2-1 wrky34-1 double mutant, compared with in wild-type. Yeast one-hybrid and dual luciferase reporter assays indicated that WRKY2 and WRKY34 recognized the MYB97 promoter by binding to its W-boxes. MYB97 overexpression caused defects in pollen germination and pollen tube length, which impacted male fertility. Thus, WRKY2/34–VQ20 complexes appear to negatively regulate the expression of certain MYBs during plant male gametogenesis.

Pleasure Experience and Emotion Expression in Patients with Schizophrenia

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CHU, Min-yi; LI, Xu; LV, Qin-yu; Yl, Zheng-hui; CHEUNG, Eric F. C.; CHAN, Raymond C. K.

2017-01-01

Background Impairments in emotional experience and expression have been observed in patients with schizophrenia. However, most previous studies have been limited to either emotional experience (especially anhedonia) or expression. Few studies have examined both the experience and expression of emotion in schizophrenia patients at the same time. Aims The present study aimed to examine pleasure experience and emotion expression in patients with schizophrenia. In particular, we specifically examined the relationship between emotion impairments (both pleasure experience and expression) and negative symptoms. Methods One hundred and fifty patients completed the Temporal Experience of Pleasure Scale and Emotional Expressivity Scale. Results Schizophrenia patients exhibited deficits in experiencing pleasure, but showed intact reported emotion expression. Patients with prominent negative symptoms showed reduced anticipatory pleasure, especially in abstract anticipatory pleasure. Conclusion The present findings suggest that patients with schizophrenia have deficits in pleasure experience, while their abilities to express emotion appear intact. Such deficits are more severe in patients with prominent negative symptoms. PMID:29276350

Negative correlation of LIV-1 and E-cadherin expression in hepatocellular carcinoma cells.

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Rongxi Shen

Full Text Available LIV-1, a zinc transporter, is a mediator downstream of STAT3 both in zebrafish and mammalian cells, and is involved in epithelial-mesenchymal transition (EMT. Despite LIV-1 participates in cancer growth and metastasis, little is known about the association of LIV-1 with human liver cancer development. Therefore, the expression of LIV-1 mRNA was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR in 4 cultured cell lines (3 carcinoma and 1 normal liver cell lines, and the localization of LIV-1 protein was investigated by immunohistochemistry. Expression of LIV-1 protein was analyzed by Western blot both in 4 cultured cell lines and 120 liver tissues (100 carcinoma and 20 histologically normal tissues, and the relationship between its expression and clinicopathological finding was investigated in 100 hepatocellular carcinoma(HCC tissues. Then stable siRNA expressing Hep-G2 cells were generated to assess the function of LIV-1 in liver cancer cells. We found that LIV-1 mRNA was more highly expressed in liver cancer cell lines compared to normal liver cell line. Western blot showed the expression of LIV-1 was higher in 61% liver carcinoma tissues than that in normal liver tissues. Down-regulated LIV-1 cells showed significant inhibition of proliferation in vitro and reduction of tumor growth in vivo. Furthermore, E-cadherin expression increased in LIV-1 siRNA expressing Hep-G2. These findings indicated that LIV-1 may induce the EMT in HCC cells.

Regular expressions cookbook

CERN Document Server

Goyvaerts, Jan

2009-01-01

This cookbook provides more than 100 recipes to help you crunch data and manipulate text with regular expressions. Every programmer can find uses for regular expressions, but their power doesn't come worry-free. Even seasoned users often suffer from poor performance, false positives, false negatives, or perplexing bugs. Regular Expressions Cookbook offers step-by-step instructions for some of the most common tasks involving this tool, with recipes for C#, Java, JavaScript, Perl, PHP, Python, Ruby, and VB.NET. With this book, you will: Understand the basics of regular expressions through a

Mental fatigue, motivation and action monitoring

NARCIS (Netherlands)

Boksem, MAS; Meijman, TF; Lorist, MM

In this study we examined whether the effects of mental fatigue on behaviour are due to reduced action monitoring as indexed by the error related negativity (Ne/ERN), N2 and contingent negative variation (CNV) event-related potential (ERP) components. Therefore, we had Subjects perform a task, which

Epileptic Negative Myoclonus as the First and Only Symptom in a Challenging Diagnosis of Benign Epilepsy With Centrotemporal Spikes

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Jing Chen MD

2017-07-01

Full Text Available Objective: To investigate the clinical and neurophysiological characteristics of epileptic negative myoclonus as the first and only ictal symptom of benign epilepsy with centrotemporal spikes. Methods: Electrophysiological evaluations included polygraphic recordings with simultaneous video electroencephalogram monitoring and tests performed with patient’s upper limb outstretched in standing posture. Epileptic negative myoclonus manifestations, electrophysiological features, and responses to antiepileptic drugs were analyzed. Results: The authors report 2 patients with benign epilepsy with centrotemporal spikes, who had epileptic negative myoclonus as the first and only seizure type. Video electroencephalogram monitoring results showed that their negative myoclonus seizures were emanating from the contralateral central and the parietal regions. Epileptic negative myoclonus was controlled by administration of valproate and levetiracetam. Conclusion: Epileptic negative myoclonus can be the first and only seizure type of benign epilepsy with centrotemporal spikes, and long-term follow-up monitoring should be the care for the recurrence and/or presence of other types of seizures.

Gene Expression Profiling Reveals a Massive, Aneuploidy-Dependent Transcriptional Deregulation and Distinct Differences between Lymph Node–Negative and Lymph Node–Positive Colon Carcinomas

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Grade, Marian; Hörmann, Patrick; Becker, Sandra; Hummon, Amanda B.; Wangsa, Danny; Varma, Sudhir; Simon, Richard; Liersch, Torsten; Becker, Heinz; Difilippantonio, Michael J.; Ghadimi, B. Michael; Ried, Thomas

2016-01-01

To characterize patterns of global transcriptional deregulation in primary colon carcinomas, we did gene expression profiling of 73 tumors [Unio Internationale Contra Cancrum stage II (n = 33) and stage III (n = 40)] using oligonucleotide microarrays. For 30 of the tumors, expression profiles were compared with those from matched normal mucosa samples. We identified a set of 1,950 genes with highly significant deregulation between tumors and mucosa samples (P 5-fold average expression difference between normal colon mucosa and carcinomas, including up-regulation of MYC and of HMGA1, a putative oncogene. Furthermore, we identified 68 genes that were significantly differentially expressed between lymph node–negative and lymph node–positive tumors (P deregulated genes were validated using quantitative real-time reverse transcription-PCR in >40 tumor and normal mucosa samples with good concordance between the techniques. Finally, we established a relationship between specific genomic imbalances, which were mapped for 32 of the analyzed colon tumors by comparative genomic hybridization, and alterations of global transcriptional activity. Previously, we had conducted a similar analysis of primary rectal carcinomas. The systematic comparison of colon and rectal carcinomas revealed a significant overlap of genomic imbalances and transcriptional deregulation, including activation of the Wnt/β-catenin signaling cascade, suggesting similar pathogenic pathways. PMID:17210682

Quantified Event Automata: Towards Expressive and Efficient Runtime Monitors

Science.gov (United States)

Barringer, Howard; Falcone, Ylies; Havelund, Klaus; Reger, Giles; Rydeheard, David

2012-01-01

Runtime verification is the process of checking a property on a trace of events produced by the execution of a computational system. Runtime verification techniques have recently focused on parametric specifications where events take data values as parameters. These techniques exist on a spectrum inhabited by both efficient and expressive techniques. These characteristics are usually shown to be conflicting - in state-of-the-art solutions, efficiency is obtained at the cost of loss of expressiveness and vice-versa. To seek a solution to this conflict we explore a new point on the spectrum by defining an alternative runtime verification approach.We introduce a new formalism for concisely capturing expressive specifications with parameters. Our technique is more expressive than the currently most efficient techniques while at the same time allowing for optimizations.

Low/Negative Expression of PDGFR-α Identifies the Candidate Primary Mesenchymal Stromal Cells in Adult Human Bone Marrow

DEFF Research Database (Denmark)

Li, Hongzhe; Ghazanfari, Roshanak; Zacharaki, Dimitra

2014-01-01

Human bone marrow (BM) contains a rare population of nonhematopoietic mesenchymal stromal cells (MSCs), which are of central importance for the hematopoietic microenvironment. However, the precise phenotypic definition of these cells in adult BM has not yet been reported. In this study, we show...... exhibited high levels of genes associated with mesenchymal lineages and HSC supportive function. Moreover, lin(-)/CD45(-)/CD271(+)/CD140a(low/-) cells effectively mediated the ex vivo expansion of transplantable CD34(+) hematopoietic stem cells. Taken together, these data indicate that CD140a is a key...... that low/negative expression of CD140a (PDGFR-α) on lin(-)/CD45(-)/CD271(+) BM cells identified a cell population with very high MSC activity, measured as fibroblastic colony-forming unit frequency and typical in vitro and in vivo stroma formation and differentiation capacities. Furthermore, these cells...

Performance Monitoring Applied to System Supervision

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Bertille Somon

2017-07-01

Full Text Available Nowadays, automation is present in every aspect of our daily life and has some benefits. Nonetheless, empirical data suggest that traditional automation has many negative performance and safety consequences as it changed task performers into task supervisors. In this context, we propose to use recent insights into the anatomical and neurophysiological substrates of action monitoring in humans, to help further characterize performance monitoring during system supervision. Error monitoring is critical for humans to learn from the consequences of their actions. A wide variety of studies have shown that the error monitoring system is involved not only in our own errors, but also in the errors of others. We hypothesize that the neurobiological correlates of the self-performance monitoring activity can be applied to system supervision. At a larger scale, a better understanding of system supervision may allow its negative effects to be anticipated or even countered. This review is divided into three main parts. First, we assess the neurophysiological correlates of self-performance monitoring and their characteristics during error execution. Then, we extend these results to include performance monitoring and error observation of others or of systems. Finally, we provide further directions in the study of system supervision and assess the limits preventing us from studying a well-known phenomenon: the Out-Of-the-Loop (OOL performance problem.

Spo0A positively regulates epr expression by negating the ...

Indian Academy of Sciences (India)

2013-03-07

Mar 7, 2013 ... ly regulate the epr expression by the process of co-repression. (Kodgire et al. 2006). ... Bacterial strains and plasmids used in this study are listed in table 1. E. coli DH5α ... Wherever necessary, antibiotics were added to the ...

The role of RCAS1 as a biomarker in diagnosing CRC and monitoring tumor recurrence and metastasis.

Science.gov (United States)

Han, Su-xia; Wang, Jing; Wang, Li-juan; Jin, Gui-hua; Ying, Xia; He, Chen-chen; Guo, Xi-jing; Zhang, Jian-ying; Zhang, Ying; Zhu, Qing

2014-06-01

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) plays an important role in tumor progression by helping tumor cell to escape from host immunological surveillance or modifying the characteristics of connective tissue around. RCAS1 may appropriately reflect the development and prognosis of tumor. In the study, we sought to identify the clinical significance of RCAS1 in colorectal cancer (CRC) diagnosis and tumor recurrence monitoring. Immunohistochemistry (IHC) with tissue array slides was preformed to analyze RCAS1 protein expression in CRC, colorectal polyps, and normal colon tissues. RCAS1 levels in colorectal cancer were significantly higher than those in colorectal polyps and normal colon tissues (PCRC are significantly higher than in healthy controls and polyps (PCRC was 82.1 %, which was higher than carcinoembryonic antigen (CEA). Especially in CEA-negative cases, the sensitivity of RCAS1 was 88.2 %. Finally, CRC patients who were followed up showed a serum RCAS1 level which significantly decreased after surgery (PCRC diagnosis but also useful for monitoring tumor recurrence. RCAS1 might be a supplementary serological marker for CRC.

Comparison of false-negative/positive results of intraoperative evoked potential monitoring between no and partial neuromuscular blockade in patients receiving propofol/remifentanil-based anesthesia during cerebral aneurysm clipping surgery: A retrospective analysis of 685 patients.

Science.gov (United States)

Kim, Sung-Hoon; Jin, Seok-Joon; Karm, Myong-Hwan; Moon, Young-Jin; Jeong, Hye-Won; Kim, Jae-Won; Ha, Seung-Il; Kim, Joung-Uk

2016-08-01

Although the elicited responses of motor evoked potential (MEP) monitoring are very sensitive to suppression by anesthetic agents and muscle relaxants, the use of neuromuscular blockade (NMB) during MEP monitoring is still controversial because of serious safety concerns and diagnostic accuracy. Here, we evaluated the incidence of unacceptable movement and compared false-negative MEP results between no and partial NMB during cerebral aneurysm clipping surgery. We reviewed patient medical records for demographic data, anesthesia regimen, neurophysiology event logs, MEP results, and clinical outcomes. Patients were divided into 2 groups according to the intraoperative use of NMB: no NMB group (n = 276) and partial NMB group (n = 409). We compared the diagnostic accuracy of MEP results to predict postoperative outcomes between both groups. Additionally, we evaluated unwanted patient movement during MEP monitoring in both groups. Of the 685 patients, 622 (90.8%) manifested no intraoperative changes in MEP and no postoperative motor deficits. Twenty patients showed postoperative neurologic deficits despite preserved intraoperative MEP. False-positive MEP results were 3.6% in the no NMB group and 3.9% in the partial NMB group (P = 1.00). False-negative MEP results were 1.1% in the no NMB group and 4.2% in the partial NMB group (P = 0.02). No spontaneous movement or spontaneous respiration was observed in either group. Propofol/remifentanil-based anesthesia without NMB decreases the stimulation intensity of MEPs, which may reduce the false-negative ratio of MEP monitoring during cerebral aneurysm surgery. Our anesthetic protocol enabled reliable intraoperative MEP recording and patient immobilization during cerebral aneurysm clipping surgery.

Is monocyte HLA-DR expression monitoring a useful tool to predict the risk of secondary infection?

Science.gov (United States)

Lukaszewicz, A-C; Faivre, V; Payen, D

2010-09-01

Downregulation of the immune response is common among Intensive Care Unit (ICU) patients after an acute inflammatory injury, whether it was septic or not. Such a modification could be seen as an adaptation to attenuate the effects of the inflammatory storm on tissues, but it exposes the subject to the risk of nosocomial infection and impairs recovery processes. The intensity of immunity downregulation is difficult to characterize, since clinical presentation is silent and non-specific, which urges the use of tools for immune monitoring. This review focuses on the use of monocyte HLA-DR expression to detect immune hyporesponsiveness and to select the appropriate immunomodulating therapy, as well as the efficiency of this technique in controlling secondary infections.

Transcription Factor Foxo1 Is a Negative Regulator of NK Cell Maturation and Function

Science.gov (United States)

Deng, Youcai; Kerdiles, Yann; Chu, Jianhong; Yuan, Shunzong; Wang, Youwei; Chen, Xilin; Mao, Hsiaoyin; Zhang, Lingling; Zhang, Jianying; Hughes, Tiffany; Deng, Yafei; Zhang, Qi; Wang, Fangjie; Zou, Xianghong; Liu, Chang-Gong; Freud, Aharon G.; Li, Xiaohui; Caligiuri, Michael A; Vivier, Eric; Yu, Jianhua

2015-01-01

SUMMARY Little is known about the role of negative regulators in controlling natural killer (NK) cell development and effector functions. Foxo1 is a multifunctional transcription factor of the forkhead family. Using a mouse model of conditional deletion in NK cells, we found that Foxo1 negatively controlled NK cell differentiation and function. Immature NK cells expressed abundant Foxo1 and little Tbx21 relative to mature NK cells, but these two transcription factors reversed their expression as NK cells proceeded through development. Foxo1 promoted NK cell homing to lymph nodes through upregulating CD62L expression, and impaired late-stage maturation and effector functions by repressing Tbx21 expression. Loss of Foxo1 rescued the defect in late-stage NK cell maturation in heterozygous Tbx21+/− mice. Collectively, our data reveal a regulatory pathway by which the negative regulator Foxo1 and the positive regulator Tbx21 play opposing roles in controlling NK cell development and effector functions. PMID:25769609

Positive- and negative-acting regulatory elements contribute to the tissue-specific expression of INNER NO OUTER, a YABBY-type transcription factor gene in Arabidopsis

Directory of Open Access Journals (Sweden)

Simon Marissa K

2012-11-01

suppress expression outside of ovules. Establishment of this pattern requires cooperation and competition between multiple positive and negative regulatory elements.

ImmunoPET of tissue factor expression in triple-negative breast cancer with a radiolabeled antibody Fab fragment

International Nuclear Information System (INIS)

Shi, Sixiang; Hong, Hao; Orbay, Hakan; Yang, Yunan; Ohman, Jakob D.; Graves, Stephen A.; Nickles, Robert J.; Liu, Bai; Wong, Hing C.; Cai, Weibo

2015-01-01

To date, there is no effective therapy for triple-negative breast cancer (TNBC), which has a dismal clinical outcome. Upregulation of tissue factor (TF) expression leads to increased patient morbidity and mortality in many solid tumor types, including TNBC. Our goal was to employ the Fab fragment of ALT-836, a chimeric anti-human TF mAb, for PET imaging of TNBC, which can be used to guide future TNBC therapy. ALT-836-Fab was generated by enzymatic papain digestion. SDS-PAGE and FACS studies were performed to evaluate the integrity and TF binding affinity of ALT-836-Fab before NOTA conjugation and 64 Cu-labeling. Serial PET imaging and biodistribution studies were carried out to evaluate the tumor targeting efficacy and pharmacokinetics in the MDA-MB-231 TNBC model, which expresses high levels of TF on the tumor cells. Blocking studies, histological assessment, as well as RT-PCR were performed to confirm TF specificity of 64 Cu-NOTA-ALT-836-Fab. ALT-836-Fab was produced with high purity, which exhibited superb TF binding affinity and specificity. Serial PET imaging revealed rapid and persistent tumor uptake of 64 Cu-NOTA-ALT-836-Fab (5.1 ± 0.5 %ID/g at 24 h post-injection; n = 4) and high tumor/muscle ratio (7.0 ± 1.2 at 24 h post-injection; n = 4), several-fold higher than that of the blocking group and tumor models that do not express significant level of TF, which was confirmed by biodistribution studies. TF specificity of the tracer was also validated by histology and RT-PCR. 64 Cu-NOTA-ALT-836-Fab exhibited prominent tissue factor targeting efficiency in MDA-MB-231 TNBC model. The use of a Fab fragment led to fast tumor uptake and good tissue/muscle ratio, which may be translated into same-day immunoPET imaging in the clinical setting to improve TNBC patient management. (orig.)

ImmunoPET of tissue factor expression in triple-negative breast cancer with a radiolabeled antibody Fab fragment.

Science.gov (United States)

Shi, Sixiang; Hong, Hao; Orbay, Hakan; Graves, Stephen A; Yang, Yunan; Ohman, Jakob D; Liu, Bai; Nickles, Robert J; Wong, Hing C; Cai, Weibo

2015-07-01

To date, there is no effective therapy for triple-negative breast cancer (TNBC), which has a dismal clinical outcome. Upregulation of tissue factor (TF) expression leads to increased patient morbidity and mortality in many solid tumor types, including TNBC. Our goal was to employ the Fab fragment of ALT-836, a chimeric anti-human TF mAb, for PET imaging of TNBC, which can be used to guide future TNBC therapy. ALT-836-Fab was generated by enzymatic papain digestion. SDS-PAGE and FACS studies were performed to evaluate the integrity and TF binding affinity of ALT-836-Fab before NOTA conjugation and (64)Cu-labeling. Serial PET imaging and biodistribution studies were carried out to evaluate the tumor targeting efficacy and pharmacokinetics in the MDA-MB-231 TNBC model, which expresses high levels of TF on the tumor cells. Blocking studies, histological assessment, as well as RT-PCR were performed to confirm TF specificity of (64)Cu-NOTA-ALT-836-Fab. ALT-836-Fab was produced with high purity, which exhibited superb TF binding affinity and specificity. Serial PET imaging revealed rapid and persistent tumor uptake of (64)Cu-NOTA-ALT-836-Fab (5.1 ± 0.5 %ID/g at 24 h post-injection; n = 4) and high tumor/muscle ratio (7.0 ± 1.2 at 24 h post-injection; n = 4), several-fold higher than that of the blocking group and tumor models that do not express significant level of TF, which was confirmed by biodistribution studies. TF specificity of the tracer was also validated by histology and RT-PCR. (64)Cu-NOTA-ALT-836-Fab exhibited prominent tissue factor targeting efficiency in MDA-MB-231 TNBC model. The use of a Fab fragment led to fast tumor uptake and good tissue/muscle ratio, which may be translated into same-day immunoPET imaging in the clinical setting to improve TNBC patient management.

ImmunoPET of tissue factor expression in triple-negative breast cancer with a radiolabeled antibody Fab fragment

Energy Technology Data Exchange (ETDEWEB)

Shi, Sixiang [University of Wisconsin, Materials Science Program, Madison, WI (United States); Hong, Hao; Orbay, Hakan; Yang, Yunan; Ohman, Jakob D. [University of Wisconsin, Department of Radiology, Madison, WI (United States); Graves, Stephen A.; Nickles, Robert J. [University of Wisconsin, Department of Medical Physics, Madison, WI (United States); Liu, Bai; Wong, Hing C. [Altor BioScience, Miramar, FL (United States); Cai, Weibo [University of Wisconsin, Materials Science Program, Madison, WI (United States); University of Wisconsin, Department of Radiology, Madison, WI (United States); University of Wisconsin, Department of Medical Physics, Madison, WI (United States); University of Wisconsin Carbone Cancer Center, Madison, WI (United States); University of Wisconsin, Departments of Radiology and Medical Physics, Madison, WI (United States)

2015-07-15

To date, there is no effective therapy for triple-negative breast cancer (TNBC), which has a dismal clinical outcome. Upregulation of tissue factor (TF) expression leads to increased patient morbidity and mortality in many solid tumor types, including TNBC. Our goal was to employ the Fab fragment of ALT-836, a chimeric anti-human TF mAb, for PET imaging of TNBC, which can be used to guide future TNBC therapy. ALT-836-Fab was generated by enzymatic papain digestion. SDS-PAGE and FACS studies were performed to evaluate the integrity and TF binding affinity of ALT-836-Fab before NOTA conjugation and {sup 64}Cu-labeling. Serial PET imaging and biodistribution studies were carried out to evaluate the tumor targeting efficacy and pharmacokinetics in the MDA-MB-231 TNBC model, which expresses high levels of TF on the tumor cells. Blocking studies, histological assessment, as well as RT-PCR were performed to confirm TF specificity of {sup 64}Cu-NOTA-ALT-836-Fab. ALT-836-Fab was produced with high purity, which exhibited superb TF binding affinity and specificity. Serial PET imaging revealed rapid and persistent tumor uptake of {sup 64}Cu-NOTA-ALT-836-Fab (5.1 ± 0.5 %ID/g at 24 h post-injection; n = 4) and high tumor/muscle ratio (7.0 ± 1.2 at 24 h post-injection; n = 4), several-fold higher than that of the blocking group and tumor models that do not express significant level of TF, which was confirmed by biodistribution studies. TF specificity of the tracer was also validated by histology and RT-PCR. {sup 64}Cu-NOTA-ALT-836-Fab exhibited prominent tissue factor targeting efficiency in MDA-MB-231 TNBC model. The use of a Fab fragment led to fast tumor uptake and good tissue/muscle ratio, which may be translated into same-day immunoPET imaging in the clinical setting to improve TNBC patient management. (orig.)

Effects of cognitive remediation on negative symptoms dimensions: exploring the role of working memory.

Science.gov (United States)

Cella, M; Stahl, D; Morris, S; Keefe, R S E; Bell, M D; Wykes, T

2017-09-04

Recent theories suggest that poor working memory (WM) may be the cognitive underpinning of negative symptoms in people with schizophrenia. In this study, we first explore the effect of cognitive remediation (CR) on two clusters of negative symptoms (i.e. expressive and social amotivation), and then assess the relevance of WM gains as a possible mediator of symptom improvement. Data were accessed for 309 people with schizophrenia from the NIMH Database of Cognitive Training and Remediation Studies and a separate study. Approximately half the participants received CR and the rest were allocated to a control condition. All participants were assessed before and after therapy and at follow-up. Expressive negative symptoms and social amotivation symptoms scores were calculated from the Positive and Negative Syndrome Scale. WM was assessed with digit span and letter-number span tests. Participants who received CR had a significant improvement in WM scores (d = 0.27) compared with those in the control condition. Improvements in social amotivation levels approached statistical significance (d = -0.19), but change in expressive negative symptoms did not differ between groups. WM change did not mediate the effect of CR on social amotivation. The results suggest that a course of CR may benefit behavioural negative symptoms. Despite hypotheses linking memory problems with negative symptoms, the current findings do not support the role of this cognitive domain as a significant mediator. The results indicate that WM improves independently from negative symptoms reduction.

Negativity of Two-Qubit System Through Spin Coherent States

International Nuclear Information System (INIS)

Berrada, K.; El Baz, M.; Hassouni, Y.; Eleuch, H.

2009-12-01

Using the negativity, we express and analyze the entanglement of two-qubit nonorthogonal pure states through the spin coherent states. We formulate this measure in terms of the amplitudes of coherent states and we give the conditions for the minimal and the maximal entanglement. We generalize this formalism to the case of a class of mixed states and show that the negativity is also a function of probabilities. (author)

Exclusion of identification by negative superposition

Directory of Open Access Journals (Sweden)

Takač Šandor

2012-01-01

Full Text Available The paper represents the first report of negative superposition in our country. Photo of randomly selected young, living woman was superimposed on the previously discovered female skull. Computer program Adobe Photoshop 7.0 was used in work. Digitilized photographs of the skull and face, after uploaded to computer, were superimposed on each other and displayed on the monitor in order to assess their possible similarities or differences. Special attention was payed to matching the same anthropometrical points of the skull and face, as well as following their contours. The process of fitting the skull and the photograph is usually started by setting eyes in correct position relative to the orbits. In this case, lower jaw gonions go beyond the face contour and gnathion is highly placed. By positioning the chin, mouth and nose their correct anatomical position cannot be achieved. All the difficulties associated with the superposition were recorded, with special emphasis on critical evaluation of work results in a negative superposition. Negative superposition has greater probative value (exclusion of identification than positive (possible identification. 100% negative superposition is easily achieved, but 100% positive - almost never. 'Each skull is unique and viewed from different perspectives is always a new challenge'. From this point of view, identification can be negative or of high probability.

Radiosensitization of head/neck squamous cell carcinoma by adenovirus-mediated expression of dominant negative constructs of the Nbs1 protein

International Nuclear Information System (INIS)

Carney, J.P.; Rhee, J.G.; Li, D.; Chen, T.; Suntharalingam, M.; O'Malley, B.W.

2001-01-01

. Conclusion: Dominant negative constructs of the Nbs1 protein are able to sensitize cells to ionizing radiation exposure. Surprisingly expression of the full-length Nbs1 protein results in enhanced sensitivity as well. These results provide a proof of principle that disruption of Nbs1 function may provide a means of enhancing the radiosensitivity of head and neck tumors

Negative refraction of inhomogeneous waves in lossy isotropic media

International Nuclear Information System (INIS)

Fedorov, V Yu; Nakajima, T

2014-01-01

We theoretically study negative refraction of inhomogeneous waves at the interface of lossy isotropic media. We obtain explicit (up to the sign) expressions for the parameters of a wave transmitted through the interface between two lossy media characterized by complex permittivity and permeability. We show that the criterion of negative refraction that requires negative permittivity and permeability can be used only in the case of a homogeneous incident wave at the interface between a lossless and lossy media. In a more general situation, when the incident wave is inhomogeneous, or both media are lossy, the criterion of negative refraction becomes dependent on an incidence angle. Most interestingly, we show that negative refraction can be realized in conventional lossy materials (such as metals) if their interfaces are properly oriented. (paper)

TmCactin plays an important role in Gram-negative and -positive bacterial infection by regulating expression of 7 AMP genes in Tenebrio molitor

Science.gov (United States)

Jo, Yong Hun; Jung Kim, Yu; Beom Park, Ki; Hwan Seong, Jeong; Gon Kim, Soo; Park, Soyi; Young Noh, Mi; Seok Lee, Yong; Soo Han, Yeon

2017-01-01

Cactin was originally identified as an interactor of the Drosophila IκB factor Cactus and shown to play a role in controlling embryonic polarity and regulating the NF-κB signaling pathway. While subsequent studies have identified the roles for Cactin in the mammalian immune response, the immune function of Cactin in insects has not been described yet. Here, we identified a Cactin gene from the mealworm beetle, Tenebrio molitor (TmCactin) and characterized its functional role in innate immunity. TmCactin was highly expressed in prepupa to last instar stages, and its expression was high in the integument and Malpighian tubules of last instar larvae and adults. TmCactin was induced in larvae after infection with different pathogens and detectable within 3 hours of infection. The highest levels of TmCactin expression were detected at 9 hours post infection. TmCactin RNAi significantly decreased the survival rates of larvae after challenge with Escherichia coli and Staphylococcus aureus, but had no significant effect after challenge with Candida albicans. Furthermore, TmCactin RNAi significantly reduced the expression of seven antimicrobial peptide genes (AMPs) after bacterial challenge. Our results suggest that TmCactin may serve as an important regulator of innate immunity, mediating AMP responses against both Gram-positive and Gram-negative bacteria in T. molitor. PMID:28418029

Understanding the positive and negative effects of emotional expressions in organizations: EASI does it

NARCIS (Netherlands)

van Kleef, G.A.

2014-01-01

Emotions have a pervasive impact on organizational behavior. They do not just influence people’s own actions; when expressed, emotions may also exert influence on other organization members who perceive the expressions. Sometimes emotional expressions have ‘symmetrical’ effects, in that positive

Retinoid Expression in Onchocercal Skin Disease: Pilot Study.

Science.gov (United States)

Mawson, Anthony R; Makunde, Williams H; Penman, Alan D; Hernandez Morales, Veronica de Los Angeles; Kalinga, Akili K; Francis, Filbert; Rubinchik, Semyon; Kibweja, Addow

2017-01-01

Based on the observation that the parasite Onchocerca volvulus selectively absorbs vitamin A from the host, and the known toxicity of vitamin A in higher concentration, it was hypothesized that dying microfilariae (mf) release their stores of vitamin A (retinoids) into the host circulation in toxic concentrations, inducing the signs and symptoms of onchocerciasis. We conducted a pilot study to test the hypothesis in Songea communities in Southern Tanzania, where mass drug administration with ivermectin had not been implemented by the time of the survey. The specific aim was to evaluate the correlation between the diagnosis of onchocerciasis and increased levels of retinoic acid at infection sites. The analysis was performed by determining copy numbers of a genome of O volvulus present in skin snip samples of persons with onchocerciacis, and correlating these numbers with expression levels of retinoic acid receptor-α (RAR-α), which is inducible by retinoic acid. Total DNA and RNA were extracted from each of 25 mf-positive and 25 mf-negative skin samples and evaluated using quantitative polymerase chain reaction with appropriate negative controls. Analysis of the samples, adjusted with glyceraldehyde 3-phosphate dehydrogenase gene levels, revealed that most samples with detectable RAR-α transcripts had higher levels of RAR-α expression than the assay control. However, the quality and number of samples were insufficient for statistical analysis. Fold data on the expression levels of both O volvulus DNA and RAR RNA suggested a possible trend toward higher relative RAR-α expression in samples with higher levels of O volvulus DNA ( r 2  = 0.25, P  = .079). Evidence of a contribution of vitamin A to the pathology of onchocerciasis thus remains elusive. Future studies on the role of retinoids in onchocerciasis will require larger groups of participants as well as careful monitoring of the cold chain and tissue storage procedures in view of the sensitivity of

Insular Activity during Passive Viewing of Aversive Stimuli Reflects Individual Differences in State Negative Affect

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Meriau, Katja; Wartenburger, Isabell; Kazzer, Philipp; Prehn, Kristin; Villringer, Arno; van der Meer, Elke; Heekeren, Hauke R.

2009-01-01

People differ with regard to how they perceive, experience, and express negative affect. While trait negative affect reflects a stable, sustained personality trait, state negative affect represents a stimulus limited and temporally acute emotion. So far, little is known about the neural systems mediating the relationship between negative affect…

When negation is not negation

OpenAIRE

Milicevic, Nataša

2008-01-01

In this paper I will discuss the formation of different types of yes/no questions in Serbian (examples in (1)), focusing on the syntactically and semantically puzzling example (1d), which involves the negative auxiliary inversion. Although there is a negative marker on the fronted auxiliary, the construction does not involve sentential negation. This coincides with the fact that the negative quantifying NPIs cannot be licensed. The question formation and sentential negation have similar synta...

17β-estradiol-induced growth of triple-negative breast cancer cells is prevented by the reduction of GPER expression after treatment with gefitinib.

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Girgert, Rainer; Emons, Günter; Gründker, Carsten

2017-02-01

Triple-negative breast cancers (TNBCs) are neither susceptible to endocrine therapy due to a lack of estrogen receptor α expression nor trastuzumab. TNBCs frequently overexpress epidermal growth factor receptor (EGFR) and membrane bound estrogen receptor, GPER. To a certain extent the growth of TNBCs is stimulated by 17β-estradiol via GPER. We analyzed whether inhibition of EGFR by gefitinib reduces the expression of GPER and subsequent signal transduction in TNBC cells. Dependence of proliferation on 17β-estradiol was determined using Alamar Blue assay. Expression of GPR30 and activation of c-src, EGFR and cAMP-responsive element binding (CREB) protein by 17β-estradiol was analyzed by western blotting. Expression of c-fos, cyclin D1 and aromatase was determined using RT-PCR. Gefitinib reduced GPER expression concentration‑ and time‑dependently. In HCC70 cells, GPER expression was reduced to 15±11% (p<0.05) after treatment with 200 nM gefitinib for four days, and in HCC1806 cells GPER expression was reduced to 39±5% (p<0.01) of the control. 17β-estradiol significantly increased the percentage of HCC1806 cells within 7 days to 145±29% of the control (HCC70, 110±8%). This increase in cell growth was completely prevented in both TNBC cell lines after GPR30 expression was downregulated by treatment with 200 nM gefitinib. In HCC1806 cells, activation of c-src was increased by 17β-estradiol to 350±50% (p<0.01), and gefitinib reduced src activation to 110%. Similar results were obtained in the HCC70 cells. Phosphorylation of EGFR increased to 240±40% (p<0.05) in the HCC1806 cells treated with 17β-estradiol (HCC70, 147±25%). Gefitinib completely prevented this activation. Phosphorylation of CREB and induction of c-fos, cyclin D1 and aromatase expression by 17β-estradiol were all prevented by gefitinib. These experiments conclusively show that reduction of GPER expression is a promising therapeutic approach for TNBC.

Flg22-Triggered Immunity Negatively Regulates Key BR Biosynthetic Genes.

Science.gov (United States)

Jiménez-Góngora, Tamara; Kim, Seong-Ki; Lozano-Durán, Rosa; Zipfel, Cyril

2015-01-01

In plants, activation of growth and activation of immunity are opposing processes that define a trade-off. In the past few years, the growth-promoting hormones brassinosteroids (BR) have emerged as negative regulators of pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI), promoting growth at the expense of defense. The crosstalk between BR and PTI signaling was described as negative and unidirectional, since activation of PTI does not affect several analyzed steps in the BR signaling pathway. In this work, we describe that activation of PTI by the bacterial PAMP flg22 results in the reduced expression of BR biosynthetic genes. This effect does not require BR perception or signaling, and occurs within 15 min of flg22 treatment. Since the described PTI-induced repression of gene expression may result in a reduction in BR biosynthesis, the crosstalk between PTI and BR could actually be negative and bidirectional, a possibility that should be taken into account when considering the interaction between these two pathways.

Noninvasive monitoring of placenta-specific transgene expression by bioluminescence imaging.

Directory of Open Access Journals (Sweden)

Xiujun Fan

Full Text Available BACKGROUND: Placental dysfunction underlies numerous complications of pregnancy. A major obstacle to understanding the roles of potential mediators of placental pathology has been the absence of suitable methods for tissue-specific gene manipulation and sensitive assays for studying gene functions in the placentas of intact animals. We describe a sensitive and noninvasive method of repetitively tracking placenta-specific gene expression throughout pregnancy using lentivirus-mediated transduction of optical reporter genes in mouse blastocysts. METHODOLOGY/PRINCIPAL FINDINGS: Zona-free blastocysts were incubated with lentivirus expressing firefly luciferase (Fluc and Tomato fluorescent fusion protein for trophectoderm-specific infection and transplanted into day 3 pseudopregnant recipients (GD3. Animals were examined for Fluc expression by live bioluminescence imaging (BLI at different points during pregnancy, and the placentas were examined for tomato expression in different cell types on GD18. In another set of experiments, blastocysts with maximum photon fluxes in the range of 2.0E+4 to 6.0E+4 p/s/cm(2/sr were transferred. Fluc expression was detectable in all surrogate dams by day 5 of pregnancy by live imaging, and the signal increased dramatically thereafter each day until GD12, reaching a peak at GD16 and maintaining that level through GD18. All of the placentas, but none of the fetuses, analyzed on GD18 by BLI showed different degrees of Fluc expression. However, only placentas of dams transferred with selected blastocysts showed uniform photon distribution with no significant variability of photon intensity among placentas of the same litter. Tomato expression in the placentas was limited to only trophoblast cell lineages. CONCLUSIONS/SIGNIFICANCE: These results, for the first time, demonstrate the feasibility of selecting lentivirally-transduced blastocysts for uniform gene expression in all placentas of the same litter and early

Face expressive lifting (FEL): an original surgical concept combined with bipolar radiofrequency.

Science.gov (United States)

Divaris, Marc; Blugerman, Guillermo; Paul, Malcolm D

2014-01-01

Aging can lead to changes in facial expressions, transforming the positive youth expression of happiness to negative expressions as sadness, tiredness, and disgust. Local skin distension is another consequence of aging, which can be difficult to treat with rejuvenation procedures. The "face expressive lifting" (FEL) is an original concept in facial rejuvenation surgery. On the one hand, FEL integrates established convergent surgical techniques aiming to correct the age-related negative facial expressions. On the other hand, FEL incorporates novel bipolar RF technology aiming to correct local skin distension. One hundred twenty-six patients underwent FEL procedure. Facial expression and local skin distension were assessed with 2 years follow-up. There was a correction of negative facial expression for 96 patients (76 %) and a tightening of local skin distension in 100 % of cases. FEL is an effective procedure taking into account and able to correct both age-related negative changes in facial expression and local skin distension using radiofrequency. Level of Evidence: Level IV, therapeutic study.

FA1 immunoreactivity in endocrine tumours and during development of the human fetal pancreas; negative correlation with glucagon expression

DEFF Research Database (Denmark)

Tornehave, D; Jensen, Charlotte Harken; Teisner, B

1996-01-01

Fetal antigen 1 (FA1) is a glycoprotein containing six epidermal growth factor (EGF)-like repeats. It is closely similar to the protein translated from the human delta-like (dlk) cDNA and probably constitutes a proteolytically processed form of dlk. dlk is homologous to the Drosophila homeotic...... proteins delta and notch and to the murine preadipocyte differentiation factor Pref-1. These proteins participate in determining cell fate choices during differentiation. We now report that FA1 immunoreactivity is present in a number of neuroectodermally derived tumours as well as in pancreatic endocrine...... tumours. A negative correlation between FA1 and glucagon immunoreactants in these tumours prompted a reexamination of FA1 immunoreactants during fetal pancreatic development. At the earliest stages of development, FA1 was expressed by most of the non-endocrine parenchymal cells and, with ensuing...

A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients.

Science.gov (United States)

Habel, Laurel A; Shak, Steven; Jacobs, Marlena K; Capra, Angela; Alexander, Claire; Pho, Mylan; Baker, Joffre; Walker, Michael; Watson, Drew; Hackett, James; Blick, Noelle T; Greenberg, Deborah; Fehrenbacher, Louis; Langholz, Bryan; Quesenberry, Charles P

2006-01-01

The Oncotype DX assay was recently reported to predict risk for distant recurrence among a clinical trial population of tamoxifen-treated patients with lymph node-negative, estrogen receptor (ER)-positive breast cancer. To confirm and extend these findings, we evaluated the performance of this 21-gene assay among node-negative patients from a community hospital setting. A case-control study was conducted among 4,964 Kaiser Permanente patients diagnosed with node-negative invasive breast cancer from 1985 to 1994 and not treated with adjuvant chemotherapy. Cases (n = 220) were patients who died from breast cancer. Controls (n = 570) were breast cancer patients who were individually matched to cases with respect to age, race, adjuvant tamoxifen, medical facility and diagnosis year, and were alive at the date of death of their matched case. Using an RT-PCR assay, archived tumor tissues were analyzed for expression levels of 16 cancer-related and five reference genes, and a summary risk score (the Recurrence Score) was calculated for each patient. Conditional logistic regression methods were used to estimate the association between risk of breast cancer death and Recurrence Score. After adjusting for tumor size and grade, the Recurrence Score was associated with risk of breast cancer death in ER-positive, tamoxifen-treated and -untreated patients (P = 0.003 and P = 0.03, respectively). At 10 years, the risks for breast cancer death in ER-positive, tamoxifen-treated patients were 2.8% (95% confidence interval [CI] 1.7-3.9%), 10.7% (95% CI 6.3-14.9%), and 15.5% (95% CI 7.6-22.8%) for those in the low, intermediate and high risk Recurrence Score groups, respectively. They were 6.2% (95% CI 4.5-7.9%), 17.8% (95% CI 11.8-23.3%), and 19.9% (95% CI 14.2-25.2%) for ER-positive patients not treated with tamoxifen. In both the tamoxifen-treated and -untreated groups, approximately 50% of patients had low risk Recurrence Score values. In this large, population-based study of lymph

Drug-resistant gram-negative uropathogens: A review.

Science.gov (United States)

Khoshnood, Saeed; Heidary, Mohsen; Mirnejad, Reza; Bahramian, Aghil; Sedighi, Mansour; Mirzaei, Habibollah

2017-10-01

Urinary tract infection(UTI) caused by Gram-negative bacteria is the second most common infectious presentation in community medical practice. Approximately 150 million people are diagnosed with UTI each year worldwide. Drug resistance in Gram-negative uropathogens is a major global concern which can lead to poor clinical outcomes including treatment failure, development of bacteremia, requirement for intravenous therapy, hospitalization, and extended length of hospital stay. The mechanisms of drug resistance in these bacteria are important due to they are often not identified by routine susceptibility tests and have an exceptional potential for outbreaks. Treatment of UTIs depends on the access to effective drugs, which is now threatened by antibiotic resistant Gram-negative uropathogens. Although several effective antibiotics with activity against highly resistant Gram-negatives are available, there is not a unique antibiotic with activity against the high variety of resistance. Therefore, antimicrobial susceptibility tests, correlation between clinicians and laboratories, development of more rapid diagnostic methods, and continuous monitoring of drug resistance are urgent priorities. In this review, we will discuss about the current global status of drug-resistant Gram-negative uropathogens and their mechanisms of drug resistance to provide new insights into their treatment options. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Diminished facial emotion expression and associated clinical characteristics in Anorexia Nervosa.

Science.gov (United States)

Lang, Katie; Larsson, Emma E C; Mavromara, Liza; Simic, Mima; Treasure, Janet; Tchanturia, Kate

2016-02-28

This study aimed to investigate emotion expression in a large group of children, adolescents and adults with Anorexia Nervosa (AN), and investigate the associated clinical correlates. One hundred and forty-one participants (AN=66, HC= 75) were recruited and positive and negative film clips were used to elicit emotion expressions. The Facial Activation Coding system (FACES) was used to code emotion expression. Subjective ratings of emotion were collected. Individuals with AN displayed less positive emotions during the positive film clip compared to healthy controls (HC). There was no significant difference between the groups on the Positive and Negative Affect Scale (PANAS). The AN group displayed emotional incongruence (reporting a different emotion to what would be expected given the stimuli, with limited facial affect to signal the emotion experienced), whereby they reported feeling significantly higher rates of negative emotion during the positive clip. There were no differences in emotion expression between the groups during the negative film clip. Despite this individuals with AN reported feeling significantly higher levels of negative emotions during the negative clip. Diminished positive emotion expression was associated with more severe clinical symptoms, which could suggest that these individuals represent a group with serious social difficulties, which may require specific attention in treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Radioactivity monitor for high-performance liquid chromatography

International Nuclear Information System (INIS)

Reeve, D.R.; Crozier, A.

1977-01-01

The coupling of a homogeneous radioactivity monitor to a liquid chromatograph involves compromises between the sensitivity of the monitor and the resolution and speed of analysis of the chromatograph. The theoretical relationships between these parameters are considered and expressions derived which make it possible to calculate suitable monitor operating conditions for most types of high-performance liquid chromatography

Extracellular matrix metalloproteinase inducer (EMMPRIN) expression correlates positively with active angiogenesis and negatively with basic fibroblast growth factor expression in epithelial ovarian cancer.

Science.gov (United States)

Szubert, Sebastian; Szpurek, Dariusz; Moszynski, Rafal; Nowicki, Michal; Frankowski, Andrzej; Sajdak, Stefan; Michalak, Slawomir

2014-03-01

The primary aim of this paper was to evaluate the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and its relationship with proangiogenic factors and microvessel density (MVD) in ovarian cancer. The study group included 58 epithelial ovarian cancers (EOCs), 35 benign ovarian tumors, and 21 normal ovaries. The expression of EMMPRIN, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) was assessed by ELISA of tissue homogenates. Antibodies against CD105, CD31, and CD34 were used to immunohistochemically assess MVD. We have found significantly higher EMMPRIN expression in EOC than in benign ovarian tumors and normal ovaries. Similarly, the VEGF expression was higher in EOC than in benign ovarian tumors and normal ovaries. By contrast, bFGF expression was lower in EOC than in benign ovarian tumors and ovary samples. EMMPRIN expression in EOC was directly correlated with VEGF expression and CD105-MVD, but inversely correlated with bFGF expression. Grade 2/3 ovarian cancers had increased expression of EMMPRIN and VEGF, increased CD105-MVD, and lowered expression of bFGF compared to grade 1 ovarian cancers. Moreover, EMMPRIN expression was higher in advanced (FIGO III and IV) ovarian cancer. The upregulation of EMMPRIN and VEGF expression is correlated with increased CD105-MVD and silenced bFGF, which suggests early and/or reactivated angiogenesis in ovarian cancer. Aggressive EOC is characterized by the following: high expression of EMMPRIN and VEGF, high CD105-MVD, and low expression of bFGF.

[Negative symptoms of schizophrenia: historical aspects].

Science.gov (United States)

Pringuey, D; Paquin, N; Cherikh, F; Giordana, B; Belzeaux, R; Cermolacce, M; Adida, M; Azorin, J-M

2015-12-01

The history of negative symptoms of schizophrenia rises early days of medicine in clinical and pathophysiological differences between positive and negative and their complex joint. Forming a set of typical core of symptoms, and some feature of a syndrome belonging to a specific pathophysiological mechanism, negative symptoms of schizophrenia emerge from old descriptions of clinical pictures, related to the overall look of madness, the heart of alienation, a central sign of early dementia, gradually more precisely describing the strange nature of the autistic withdrawal and schizophrenic apragmatism. At therapeutic era, negative symptoms have taken over the positive symptoms to establish an operational criteria whose importance lies in the progressive severity of this clinical type and in their contribution to therapeutic resistance. Despite the efforts of modern typological classifications, this work rehabilitates the old concept of "unitary psychosis" by defining a common symptomatic core to multiple clinical forms of psychosis, combining deficit of emotional expression and avolition, meaning a native psychopathology and a pathophysiology possibly in a common final way, and calling the arrival of new treatment strategies. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Downregulation of Smurf2, a tumor-suppressive ubiquitin ligase, in triple-negative breast cancers: Involvement of the RB-microRNA axis

International Nuclear Information System (INIS)

Liu, Xianpeng; Gu, Xin; Sun, Limin; Flowers, Ashley B; Rademaker, Alfred W; Zhou, Yiran; Kiyokawa, Hiroaki

2014-01-01

The HECT family ubiquitin ligase Smurf2 regulates cell polarity, migration, division, differentiation and death, by targeting diverse substrates that are critical for receptor signaling, cytoskeleton, chromatin remodeling and transcription. Recent studies suggest that Smurf2 functions as a tumor suppressor in mice. However, no inactivating mutation of SMURF2 has been reported in human, and information about Smurf2 expression in human cancer remains limited or complicated. Here we demonstrate that Smurf2 expression is downregulated in human breast cancer tissues, especially of the triple-negative subtype, and address the mechanism of Smurf2 downregulation in triple-negative breast cancer cells. Human breast cancer tissues (47 samples expressing estrogen receptor (ER) and 43 samples with triple-negative status) were examined by immunohistochemistry for the expression of Smurf2. Ten widely-studied human breast cancer cell lines were examined for the expression of Smurf2. Furthermore, microRNA-mediated regulation of Smurf2 was investigated in triple-negative cancer cell lines. Immunohistochemical analysis showed that benign mammary epithelial cells expressed high levels of Smurf2, so did cells in ductal carcinomas in situ. In contrast, invasive ductal carcinomas showed focal or diffuse decrease in Smurf2 expression, which was observed more frequently in triple-negative tumors than in ER-positive tumors. Consistently, human triple-negative breast cancer cell lines such as BT549, MDA-MB-436, DU-4475 and MDA-MB-468 cells showed significantly lower expression of Smurf2 protein, compared to ER + or HER2+ cell lines. Studies using quantitative PCR and specific microRNA inhibitors indicated that increased expression of miR-15a, miR-15b, miR-16 and miR-128 was involved in Smurf2 downregulation in those triple-negative cancer cell lines, which have mutations in the retinoblastoma (RB) gene. Forced expression of RB increased levels of Smurf2 protein with concomitant decreases in

Neuroticism modulates amygdala-prefrontal connectivity in response to negative emotional facial expressions

NARCIS (Netherlands)

Cremers, Henk R.; Demenescu, Liliana R.; Aleman, Andre; Renken, Remco; van Tol, Marie-Jose; van der Wee, Nic J. A.; Veltman, Dick. J.; Roelofs, Karin

2010-01-01

Neuroticism is associated with the experience of negative affect and the development of affective disorders. While evidence exists for a modulatory role of neuroticism on task induced brain activity, it is unknown how neuroticism affects brain connectivity, especially the crucial coupling between

Facial dynamics and emotional expressions in facial aging treatments.

Science.gov (United States)

Michaud, Thierry; Gassia, Véronique; Belhaouari, Lakhdar

2015-03-01

Facial expressions convey emotions that form the foundation of interpersonal relationships, and many of these emotions promote and regulate our social linkages. Hence, the facial aging symptomatological analysis and the treatment plan must of necessity include knowledge of the facial dynamics and the emotional expressions of the face. This approach aims to more closely meet patients' expectations of natural-looking results, by correcting age-related negative expressions while observing the emotional language of the face. This article will successively describe patients' expectations, the role of facial expressions in relational dynamics, the relationship between facial structures and facial expressions, and the way facial aging mimics negative expressions. Eventually, therapeutic implications for facial aging treatment will be addressed. © 2015 Wiley Periodicals, Inc.

Value activity monitoring

NARCIS (Netherlands)

de Alencar Silva, P.

2013-01-01

Current value modeling ontologies are grounded on the economic premise that profit sharing is a critical condition to be assessed during the configuration of a value constellation. Such a condition ought to be reinforced through a monitoring mechanism design, since a value model expresses only

Negative regulation of neuromedin U mRNA expression in the rat pars tuberalis by melatonin.

Directory of Open Access Journals (Sweden)

Sayaka Aizawa

Full Text Available The pars tuberalis (PT is part of the anterior pituitary gland surrounding the median eminence as a thin cell layer. The characteristics of PT differ from those of the pars distalis (PD, such as cell composition and gene expression, suggesting that the PT has a unique physiological function compared to the PD. Because the PT highly expresses melatonin receptor type 1, it is considered a mediator of seasonal and/or circadian signals of melatonin. Expression of neuromedin U (NMU that is known to regulate energy balance has been previously reported in the rat PT; however, the regulatory mechanism of NMU mRNA expression and secretion in the PT are still obscure. In this study, we examined both the diurnal change of NMU mRNA expression in the rat PT and the effects of melatonin on NMU in vivo. In situ hybridization and quantitative PCR analysis of laser microdissected PT samples revealed that NMU mRNA expression in the PT has diurnal variation that is high during the light phase and low during the dark phase. Furthermore, melatonin administration significantly suppressed NMU mRNA expression in the PT in vivo. On the other hand, 48 h fasting did not have an effect on PT-NMU mRNA expression, and the diurnal change of NMU mRNA expression was maintained. We also found the highest expression of neuromedin U receptor type 2 (NMUR2 mRNA in the third ventricle ependymal cell layer, followed by the arcuate nucleus and the spinal cord. These results suggest that NMU mRNA expression in the PT is downregulated by melatonin during the dark phase and shows diurnal change. Considering that NMU mRNA in the PT showed the highest expression level in the brain, PT-NMU may act on NMUR2 in the brain, especially in the third ventricle ependymal cell layer, with a circadian rhythm.

Genome-wide association studies identify four ER negative-specific breast cancer risk loci

NARCIS (Netherlands)

Garcia-Closas, Montserrat; Couch, Fergus J.; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K.; Brook, Mark N.; Orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather S.; Le Marchand, Loic; Buring, Julie E.; Eccles, Diana; Miron, Penelope; Fasching, Peter A.; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K.; Nevanlinna, Heli; Giles, Graham G.; Cox, Angela; Hopper, John L.; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J.; Schoof, Nils; Bojesen, Stig E.; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L.; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J.; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S.; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H.; Radice, Paolo; teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C.; Park, Daniel J.; Hammet, Fleur; Stone, Jennifer; Veer, Laura J. Van't; Rutgers, Emiel J.; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G.; Ekici, Arif B.; Beckmann, Matthias W.; dos Santos Silva, Isabel; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Milne, Roger L.; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N.; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Balleine, Rosemary; Tseng, Chiu-Chen; Berg, David Van Den; Stram, Daniel O.; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E.; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; McLean, Catriona; Coetzee, Gerhard A.; Feng, Ye; Henderson, Brian E.; Schumacher, Fredrick; Bogdanova, Natalia V.; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A. E. M.; Seynaeve, Caroline M.; Kriege, Mieke; Hooning, Maartje J.; van den Ouweland, Ans M. W.; van Deurzen, Carolien H. M.; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P.; Cross, Simon S.; Reed, Malcolm W. R.; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C.; González-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B.; Bandera, Elisa V.; John, Esther M.; Chen, Gary K.; Hu, Jennifer J.; Rodriguez-Gil, Jorge L.; Bernstein, Leslie; Press, Michael F.; Ziegler, Regina G.; Millikan, Robert M.; Deming-Halverson, Sandra L.; Nyante, Sarah; Ingles, Sue A.; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K.; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G.; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G.; Montgomery, Grant W.; Slamon, Dennis J.; Rauh, Claudia; Lux, Michael P.; Jud, Sebastian M.; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H.; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N.; Chen, Constance; Beck, Andy; Hankinson, Susan E.; Berg, Christine D.; Hoover, Robert N.; Lissowska, Jolanta; Figueroa, Jonine D.; Chasman, Daniel I.; Gaudet, Mia M.; Diver, W. Ryan; Willett, Walter C.; Hunter, David J.; Simard, Jacques; Benitez, Javier; Dunning, Alison M.; Sherman, Mark E.; Chenevix-Trench, Georgia; Chanock, Stephen J.; Hall, Per; Pharoah, Paul D. P.; Vachon, Celine; Easton, Douglas F.; Haiman, Christopher A.; Kraft, Peter

2013-01-01

Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including

99mTc-Labeled Cyclic RGD Peptides for Noninvasive Monitoring of Tumor Integrin αvβ3 Expression

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Yang Zhou

2011-09-01

Full Text Available This report describes the biologic evaluations of [99mTc(HYNIC-3P-RGD2(tricine(TPPTS] (99mTc-3P-RGD2: 6-hydrazinonicotinyl; 3P-RGD2 = PEG4-E[PEG4-c(RGDfK]2; PEG4 = 15-amino-4,7,10,13-tetraoxapentadecanoic acid; and TPPTS = trisodium triphenylpho-sphine-3,3′,3“-trisulfonate, [99mTc(HYNIC-3G-RGD2(tricine(TPPTS] (99mTc-3G-RGD2: 3G-RGD2 = G3-E[G3-c(RGDfK]2 and G3 = Gly-Gly-Gly, and 99mTcO(MAG2−3G-RGD2 (MAG2 = mercaptoacetylglycylglycyl as radiotracers for noninvasive imaging of tumor integrin αvβ3 expression in five xenografted tumor-bearing models. Biodistribution and imaging studies were performed in athymic nude mice bearing U87MG, MDA-MB-435, A549, HT29, or PC-3 tumor xenografts. Immunochemistry was performed using the cultured primary tumor cells and xenografted tumor tissues. It was found that the radiotracer tumor uptake followed the trend U87MG > MDA-MB-435 ≈ HT29 ≈ A549 > PC-3. The total integrin β3 expression levels followed the general trend: U87MG > MDA-MB-435 ≈ A549~HT29 > PC-3. There is a linear relationship between the radiotracer injected dose per gram tumor uptake and the total integrin β3 expression levels. On the basis of these, it was concluded that radiotracer tumor uptake is contributed by integrin αVβ3 expressed on tumor cells and activated endothelial cells of the tumor neovasculature. 99mTc-3P-RGD2 has the capability to monitor integrin αvβ3 expression in a noninvasive fashion.

"What concerns me is..." Expression of emotion by advanced cancer patients during outpatient visits.

Science.gov (United States)

Anderson, Wendy G; Alexander, Stewart C; Rodriguez, Keri L; Jeffreys, Amy S; Olsen, Maren K; Pollak, Kathryn I; Tulsky, James A; Arnold, Robert M

2008-07-01

Cancer patients have high levels of distress, yet oncologists often do not recognize patients' concerns. We sought to describe how patients with advanced cancer verbally express negative emotion to their oncologists. As part of the Studying Communication in Oncologist-Patient Encounters Trial, we audio-recorded 415 visits that 281 patients with advanced cancer made to their oncologists at three US cancer centers. Using qualitative methodology, we coded for verbal expressions of negative emotion, identified words patients used to express emotion, and categorized emotions by type and content. Patients verbally expressed negative emotion in 17% of the visits. The most commonly used words were: "concern," "scared," "worried," "depressed," and "nervous." Types of emotion expressed were: anxiety (46%), fear (25%), depression (12%), anger (9%), and other (8%). Topics about which emotion was expressed were: symptoms and functional concerns (66%), medical diagnoses and treatments (54%), social issues (14%), and the health care system (9%). Although all patients had terminal cancer, they expressed negative emotion overtly related to death and dying only 2% of the time. Patients infrequently expressed negative emotion to their oncologists. When they did, they typically expressed anxiety and fear, indicating concern about the future. When patients use emotionally expressive words such as those we described, oncologists should respond empathically, allowing patients to express their distress and concerns more fully.

Metaplastic Breast Cancer and EGFR Expression

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Nilufer Avci

2014-03-01

Full Text Available Aim: Metaplastic breast cancer has poor prognosis and is usually triple negative. Although it is morphologically more heterogeneous than triple negative breast cancers, expression profile is more homogeneous. In this study, we investigated our metaplastic breast cancer cases regarding their pathology and clinical characteristics. Material and Method: 16 metaplastic breast cancer cases from four different center were included in the study. Pathology and clinical characteristics of the cases were evaluated retrospectively. Results: All the cases are female and median age is 48 (39-45. Tumor is commonly localized to the outer quadrant and mean diameter of the mass is 37.5 (15-100 mm. Tumor diameter is ≤20 mm in 3 (15.8%, >20-≤50 mm in 11 (57.9% and >50 mm in 3 (10.51% of the cases. Only 4 (16.1% patients have axillary lymph node involvement. When considering histological subtypes, five of the cases has squamous cell, five of them has spindle cell, one of them has mucoepidermoid, and in five cases the subtype was not identified. Considering hormone receptor status ER and PR was negative in 78.9%, 63.2% respectively. HER2 protein expression was positive by immunohistochemical staining in 1 (5.3% case. CK5/6 and CK17 was both positive in 7 (36.8% cases. EGFR expression was positive in 4 (21.1% cases, was negative in 5 (26.3% cases and not identified in 7 (36.8% cases. Three of the cases were offered neoadjuvant chemotherapy. As neoadjuvant chemotherapy, anthracycline and taxane combination (n:2 TAC, n:1 AC-paclitaxel was preferred. Mean follow-up was 41 months. Mean survival was 42.4 months in EGFR negative patients and 47.5 months in EGFR positive patients. This difference was not statistically significant. During follow-up 3 cases had recurrence. Discussion: EGFR expression is seen in metaplastic breast cancer. Although EGFR expression is related to poor prognosis, it is not a predictive marker. Therefore, predictive molecular markers are

Visual-spatial processing and working-memory load as a function of negative and positive psychotic-like experiences.

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Abu-Akel, A; Reniers, R L E P; Wood, S J

2016-09-01

Patients with schizophrenia show impairments in working-memory and visual-spatial processing, but little is known about the dynamic interplay between the two. To provide insight into this important question, we examined the effect of positive and negative symptom expressions in healthy adults on perceptual processing while concurrently performing a working-memory task that requires the allocations of various degrees of cognitive resources. The effect of positive and negative symptom expressions in healthy adults (N = 91) on perceptual processing was examined in a dual-task paradigm of visual-spatial working memory (VSWM) under three conditions of cognitive load: a baseline condition (with no concurrent working-memory demand), a low VSWM load condition, and a high VSWM load condition. Participants overall performed more efficiently (i.e., faster) with increasing cognitive load. This facilitation in performance was unrelated to symptom expressions. However, participants with high-negative, low-positive symptom expressions were less accurate in the low VSWM condition compared to the baseline and the high VSWM load conditions. Attenuated, subclinical expressions of psychosis affect cognitive performance that is impaired in schizophrenia. The "resource limitations hypothesis" may explain the performance of the participants with high-negative symptom expressions. The dual-task of visual-spatial processing and working memory may be beneficial to assessing the cognitive phenotype of individuals with high risk for schizophrenia spectrum disorders.

Entanglement negativity and entropy in non-equilibrium conformal field theory

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Marianne Hoogeveen

2015-09-01

Full Text Available We study the dynamics of the entanglement in one-dimensional critical quantum systems after a local quench in which two independently thermalized semi-infinite halves are joined to form a homogeneous infinite system and left to evolve unitarily. We show that under certain conditions a nonequilibrium steady state (NESS is reached instantaneously as soon as the entanglement interval is within the light cone emanating from the contact point. In this steady state, the exact expressions for the entanglement entropy and the logarithmic negativity are in agreement with the steady state density matrix being a boosted thermal state, as expected. We derive various general identities: relating the negativity after the quench with unequal left and right initial temperatures with that where the left and right temperatures are equal; and relating these with the negativity in equilibrium thermal states. In certain regimes the resulting expressions can be analytically evaluated. Immediately after the interval intersects the light cone, we find logarithmic growth. For a very long interval, we find that the negativity approaches a plateau after sufficiently long times, different from its NESS value. The NESS value is reached instantly as soon as the entire interval is contained in the light cone. This provides a theoretical framework explaining recently obtained numerical results.

Entanglement negativity and entropy in non-equilibrium conformal field theory

International Nuclear Information System (INIS)

Hoogeveen, Marianne; Doyon, Benjamin

2015-01-01

We study the dynamics of the entanglement in one-dimensional critical quantum systems after a local quench in which two independently thermalized semi-infinite halves are joined to form a homogeneous infinite system and left to evolve unitarily. We show that under certain conditions a nonequilibrium steady state (NESS) is reached instantaneously as soon as the entanglement interval is within the light cone emanating from the contact point. In this steady state, the exact expressions for the entanglement entropy and the logarithmic negativity are in agreement with the steady state density matrix being a boosted thermal state, as expected. We derive various general identities: relating the negativity after the quench with unequal left and right initial temperatures with that where the left and right temperatures are equal; and relating these with the negativity in equilibrium thermal states. In certain regimes the resulting expressions can be analytically evaluated. Immediately after the interval intersects the light cone, we find logarithmic growth. For a very long interval, we find that the negativity approaches a plateau after sufficiently long times, different from its NESS value. The NESS value is reached instantly as soon as the entire interval is contained in the light cone. This provides a theoretical framework explaining recently obtained numerical results

The therapeutic effect of negative pressure in treating femoral head necrosis in rabbits.

Science.gov (United States)

Zhang, Yin-gang; Wang, Xuezhi; Yang, Zhi; Zhang, Hong; Liu, Miao; Qiu, Yushen; Guo, Xiong

2013-01-01

Because negative pressure can stimulate vascular proliferation, improve blood circulation and promote osteogenic differentiation of bone marrow stromal cells, we investigated the therapeutic effect of negative pressure on femoral head necrosis (FHN) in a rabbit model. Animals were divided into four groups (n = 60/group): [1] model control, [2] core decompression, [3] negative pressure and [4] normal control groups. Histological investigation revealed that at 4 and 8 weeks postoperatively, improvements were observed in trabecular bone shape, empty lacunae and numbers of bone marrow hematopoietic cells and fat cells in the negative pressure group compared to the core decompression group. At week 8, there were no significant differences between the negative pressure and normal control groups. Immunohistochemistry staining revealed higher expression of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2) in the femoral heads in the negative pressure group compared with the core decompression group. Transmission electron microscopy revealed that cell organelles were further developed in the negative pressure group compared with the core decompression group. Microvascular ink staining revealed an increased number of bone marrow ink-stained blood vessels, a thicker vascular lumen and increased microvascular density in the negative pressure group relative to the core decompression group. Real-time polymerase chain reaction revealed that expression levels of both VEGF and BMP-2 were higher in the negative pressure group compared with the core decompression group. In summary, negative pressure has a therapeutic effect on FHN. This effect is superior to core decompression, indicating that negative pressure is a potentially valuable method for treating early FHN.

Entropies of negative incomes, Pareto-distributed loss, and financial crises.

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Gao, Jianbo; Hu, Jing; Mao, Xiang; Zhou, Mi; Gurbaxani, Brian; Lin, Johnny

2011-01-01

Health monitoring of world economy is an important issue, especially in a time of profound economic difficulty world-wide. The most important aspect of health monitoring is to accurately predict economic downturns. To gain insights into how economic crises develop, we present two metrics, positive and negative income entropy and distribution analysis, to analyze the collective "spatial" and temporal dynamics of companies in nine sectors of the world economy over a 19 year period from 1990-2008. These metrics provide accurate predictive skill with a very low false-positive rate in predicting downturns. The new metrics also provide evidence of phase transition-like behavior prior to the onset of recessions. Such a transition occurs when negative pretax incomes prior to or during economic recessions transition from a thin-tailed exponential distribution to the higher entropy Pareto distribution, and develop even heavier tails than those of the positive pretax incomes. These features propagate from the crisis initiating sector of the economy to other sectors.

Entropies of negative incomes, Pareto-distributed loss, and financial crises.

Directory of Open Access Journals (Sweden)

Jianbo Gao

Full Text Available Health monitoring of world economy is an important issue, especially in a time of profound economic difficulty world-wide. The most important aspect of health monitoring is to accurately predict economic downturns. To gain insights into how economic crises develop, we present two metrics, positive and negative income entropy and distribution analysis, to analyze the collective "spatial" and temporal dynamics of companies in nine sectors of the world economy over a 19 year period from 1990-2008. These metrics provide accurate predictive skill with a very low false-positive rate in predicting downturns. The new metrics also provide evidence of phase transition-like behavior prior to the onset of recessions. Such a transition occurs when negative pretax incomes prior to or during economic recessions transition from a thin-tailed exponential distribution to the higher entropy Pareto distribution, and develop even heavier tails than those of the positive pretax incomes. These features propagate from the crisis initiating sector of the economy to other sectors.

Integrated expression analysis of muscle hypertrophy identifies Asb2 as a negative regulator of muscle mass

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Davey, Jonathan R.; Watt, Kevin I.; Parker, Benjamin L.; Chaudhuri, Rima; Ryall, James G.; Cunningham, Louise; Qian, Hongwei; Sartorelli, Vittorio; Chamberlain, Jeffrey; James, David E.

2016-01-01

The transforming growth factor-β (TGF-β) signaling network is a critical regulator of skeletal muscle mass and function and, thus, is an attractive therapeutic target for combating muscle disease, but the underlying mechanisms of action remain undetermined. We report that follistatin-based interventions (which modulate TGF-β network activity) can promote muscle hypertrophy that ameliorates aging-associated muscle wasting. However, the muscles of old sarcopenic mice demonstrate reduced response to follistatin compared with healthy young-adult musculature. Quantitative proteomic and transcriptomic analyses of young-adult muscles identified a transcription/translation signature elicited by follistatin exposure, which included repression of ankyrin repeat and SOCS box protein 2 (Asb2). Increasing expression of ASB2 reduced muscle mass, thereby demonstrating that Asb2 is a TGF-β network–responsive negative regulator of muscle mass. In contrast to young-adult muscles, sarcopenic muscles do not exhibit reduced ASB2 abundance with follistatin exposure. Moreover, preventing repression of ASB2 in young-adult muscles diminished follistatin-induced muscle hypertrophy. These findings provide insight into the program of transcription and translation events governing follistatin-mediated adaptation of skeletal muscle attributes and identify Asb2 as a regulator of muscle mass implicated in the potential mechanistic dysfunction between follistatin-mediated muscle growth in young and old muscles. PMID:27182554

Subliminal and supraliminal processing of facial expression of emotions: brain oscillation in the left/right frontal area.

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Balconi, Michela; Ferrari, Chiara

2012-03-26

The unconscious effects of an emotional stimulus have been highlighted by a vast amount of research, whereover it remains questionable whether it is possible to assign a specific function to cortical brain oscillations in the unconscious perception of facial expressions of emotions. Alpha band variation was monitored within the right- and left-cortical side when subjects consciously (supraliminal stimulation) or unconsciously (subliminal stimulation) processed facial patterns. Twenty subjects looked at six facial expressions of emotions (anger, fear, surprise, disgust, happiness, sadness, and neutral) under two different conditions: supraliminal (200 ms) vs. subliminal (30 ms) stimulation (140 target-mask pairs for each condition). The results showed that conscious/unconscious processing and the significance of the stimulus can modulate the alpha power. Moreover, it was found that there was an increased right frontal activity for negative emotions vs. an increased left response for positive emotion. The significance of facial expressions was adduced to elucidate cortical different responses to emotional types.

Subliminal and Supraliminal Processing of Facial Expression of Emotions: Brain Oscillation in the Left/Right Frontal Area

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Michela Balconi

2012-03-01

Full Text Available The unconscious effects of an emotional stimulus have been highlighted by a vast amount of research, whereover it remains questionable whether it is possible to assign a specific function to cortical brain oscillations in the unconscious perception of facial expressions of emotions. Alpha band variation was monitored within the right- and left-cortical side when subjects consciously (supraliminal stimulation or unconsciously (subliminal stimulation processed facial patterns. Twenty subjects looked at six facial expressions of emotions (anger, fear, surprise, disgust, happiness, sadness, and neutral under two different conditions: supraliminal (200 ms vs. subliminal (30 ms stimulation (140 target-mask pairs for each condition. The results showed that conscious/unconscious processing and the significance of the stimulus can modulate the alpha power. Moreover, it was found that there was an increased right frontal activity for negative emotions vs. an increased left response for positive emotion. The significance of facial expressions was adduced to elucidate cortical different responses to emotional types.

Studies of Wilms’ Tumor (WT1 Gene Expression in Adult Acute Leukemias in Singapore

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Che Kang Lim

2007-01-01

Full Text Available Biomarkers provide certain values for diagnosis, monitor treatment effi cacy, or for the development of novel therapeutic approach for particular diseases. Thus, the identifi cation of specifi c of biomarkers for specifi c medical problems, including malignant diseases may be valuable in medical practice. In the study, we have used the Wilms’ tumor gene (WT1 as a biomarker to evaluate its expression in local adult patients with newly diagnosed acute leukemia, including both acute myeloid and lymphoid leukemias (AML and ALL.Aim: To investigate WT1 gene expression in adult patients with acute leukemia at diagnosis.Methods: Eighteen patients with acute leukemia diagnosed at Singapore General Hospital, Singapore, between September, 2004 and July, 2005 were included in this study. There were fifteen AML and three ALL cases aged from 18 to 71 years old. Total RNA and DNA was extracted from peripheral blood mononuclear cells (PBMCs. Expression of WT1 was detected by nested reverse-transcription polymerase chain reaction (Nested RT-PCR. K562, and 3T3 cells were used as positive- and negative-controls. The results were revalidated using real-time PCR. HLA-A genotyping was performed using sequence specific oligonucleotide polymorphism (SSOP analysis.Results: WT1 gene was exclusively expressed in all eighteen, including three ALL and fi fteen AML, patients. In contrast with WT1 gene, the HLA-A genotyping was remarkably heterogeneous in these patients.Conclusions: WT1 gene expression was observed in local patients with acute leukemia at diagnosis. It may be used as a potential molecular marker for diagnosis, clinical progression of the diseases or monitoring the response to treatment, as well as a target for the development of novel therapeutic approaches.

The free energy principle, negative energy modes, and stability

International Nuclear Information System (INIS)

Morrison, P.J.; Kotschenreuther, M.

1990-01-01

This paper is concerned with instability of equilibria of Hamiltonian, fluid and plasma dynamical systems. Usually the dynamical equilibrium of interest is not the state of thermodynamic equilibrium, and does not correspond to a free energy minimum. The relaxation of this type of equilibrium is conventionally considered to be initiated by linear instability. However, there are many cases where linear instability is not present, but the equilibrium is nonlinearly unstable to arbitrarily small perturbations. This paper is about general free energy expressions for determining the presence of linear or nonlinear instabilities. These expressions are simple and practical, and can be obtained for all equilibria of all ideal fluid and plasma models. By free energy, we mean the energy change upon perturbations of the equilibrium that respect dynamical phase space constraints. This quantity is measured by a self-adjoint quadratic form, called δ 2 F. The free energy can result in instability when δ 2 F is indefinite; i.e. there exist accessible perturbations that lower the free energy of the system. A primary purpose of this paper is to tie together three manifestations of what we will refer to as negative energy modes. The first is the conventional plasma physics notion of negative energy mode that is based on the definition of the energy in a homogeneous dielectric medium. A negative energy mode is a normal mode of the medium (plasma) that possesses negative dielectric energy. The second manifestation occurs in finite degree-of-freedom Hamiltonian normal form theory. The quadratic part of a Hamiltonian in the vicinity of an equilibrium point, which possesses only distinct oscillatory eigenvalues, has an invariant signature. Thus in cases where the quadratic form is indefinite, it is natural to refer to the modes corresponding to the negative signature as negative energy modes

High mobility group protein DSP1 negatively regulates HSP70 transcription in Crassostrea hongkongensis

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Miao, Zongyu; Xu, Delin; Cui, Miao; Zhang, Qizhong, E-mail: zhangqzdr@126.com

2016-06-10

HSP70 acts mostly as a molecular chaperone and plays important roles in facilitating the folding of nascent peptides as well as the refolding or degradation of the denatured proteins. Under stressed conditions, the expression level of HSP70 is upregulated significantly and rapidly, as is known to be achieved by various regulatory factors controlling the transcriptional level. In this study, a high mobility group protein DSP1 was identified by DNA-affinity purification from the nuclear extracts of Crassostrea hongkongensis using the ChHSP70 promoter as a bait. The specific interaction between the prokaryotically expressed ChDSP1 and the FITC-labeled ChHSP70 promoter was confirmed by EMSA analysis. ChDSP1 was shown to negatively regulate ChHSP70 promoter expression by Luciferase Reporter Assay in the heterologous HEK293T cells. Both ChHSP70 and ChDSP1 transcriptions were induced by either thermal or CdCl{sub 2} stress, while the accumulated expression peaks of ChDSP1 were always slightly delayed when compared with that of ChHSP70. This indicates that ChDSP1 is involved, very likely to exert its suppressive role, in the recovery of the ChHSP70 expression from the induced level to its original state. This study is the first to report negative regulator of HSP70 gene transcription, and provides novel insights into the mechanisms controlling heat shock protein expression. -- Highlights: •HMG protein ChDSP1 shows affinity to ChHSP70 promoter in Crassostrea hongkongensis. •ChDSP1 negatively regulates ChHSP70 transcription. •ChHSP70 and ChDSP1 transcriptions were coordinately induced by thermal/Cd stress. •ChDSP1 may contribute to the recovery of the induced ChHSP70 to its original state. •This is the first report regarding negative regulator of HSP70 transcription.

Social inhibition modulates the effect of negative emotions on cardiac prognosis following percutaneous coronary intervention in the drug-eluting stent era

DEFF Research Database (Denmark)

Denollet, Johan; Pedersen, Susanne S.; Ong, Andrew T L

2006-01-01

Negative emotions have an adverse effect on cardiac prognosis. We investigated whether social inhibition (inhibited self-expression in social interaction) modulates the effect of negative emotions on clinical outcome following percutaneous coronary intervention (PCI).......Negative emotions have an adverse effect on cardiac prognosis. We investigated whether social inhibition (inhibited self-expression in social interaction) modulates the effect of negative emotions on clinical outcome following percutaneous coronary intervention (PCI)....

Negation and Nonveridicality in the History of Greek

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Chatzopoulou, Aikaterini

2012-01-01

This study provides a thorough investigation of the expression primarily of sentential negation in the history of Greek, through quantitative data from representative texts from three major stages of vernacular Greek (Attic Greek, Koine, Late Medieval Greek), and qualitative data from Homeric Greek until Standard Modern. The contrast between two…

Mothers' depressive symptoms predict both increased and reduced negative reactivity: aversion sensitivity and the regulation of emotion.

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Dix, Theodore; Moed, Anat; Anderson, Edward R

2014-07-01

This study examined whether, as mothers' depressive symptoms increase, their expressions of negative emotion to children increasingly reflect aversion sensitivity and motivation to minimize ongoing stress or discomfort. In multiple interactions over 2 years, negative affect expressed by 319 mothers and their children was observed across variations in mothers' depressive symptoms, the aversiveness of children's immediate behavior, and observed differences in children's general negative reactivity. As expected, depressive symptoms predicted reduced maternal negative reactivity when child behavior was low in aversiveness, particularly with children who were high in negative reactivity. Depressive symptoms predicted high negative reactivity and steep increases in negative reactivity as the aversiveness of child behavior increased, particularly when high and continued aversiveness from the child was expected (i.e., children were high in negative reactivity). The findings are consistent with the proposal that deficits in parenting competence as depressive symptoms increase reflect aversion sensitivity and motivation to avoid conflict and suppress children's aversive behavior. © The Author(s) 2014.

Negative absorption in an anisotropic plasma

Energy Technology Data Exchange (ETDEWEB)

Karapetyan, R.V.

1976-02-01

We consider the absorption of electromagnetic waves in a plasma with electron drift for an arbitrary relation between the electron thermal and drift velocities and also for an arbitrary angle between the polarization vector of the wave and the direction of drift. Using a kinetic equation describing the influence of an external field on the collision of plasma particles, we find an expression for the work done on the plasma by a high-frequency electromagnetic field of arbitrary intensity. We show that in the weak-field limit under certain conditions the sign of the work becomes negative; i.e., a plasma with electron drift can amplify electromagnetic waves propagating through it. An expression is obtained for the amplification coefficient and a numerical estimate is given. (AIP)

Advances of reporter gene imaging monitoring stem cell therapy

International Nuclear Information System (INIS)

Pei Zhijun; Zhang Yongxue

2010-01-01

Stem cell transplantation in the treatment of various tissue damage or degenerative diseases are research hotspots both at home and abroad. However, ignorance of the homing, differentiation and functional expression of the stem cell in vivo influence the further development of stem cell therapy. As an important component of molecular imaging technology, reporter gene imaging dynamically monitors the change of stem cell in vivo via monitoring the expression of transfected reporter gene. This paper briefly describes the latest research progress and the future development trend of the monitoring of reporter gene imaging in stem cell therapy in vivo. (authors)

Loss of the NKX3.1 tumorsuppressor promotes the TMPRSS2-ERG fusion gene expression in prostate cancer

International Nuclear Information System (INIS)

Thangapazham, Rajesh; Saenz, Francisco; Katta, Shilpa; Mohamed, Ahmed A; Tan, Shyh-Han; Petrovics, Gyorgy; Srivastava, Shiv; Dobi, Albert

2014-01-01

In normal prostate epithelium the TMPRSS2 gene encoding a type II serine protease is directly regulated by male hormones through the androgen receptor. In prostate cancer ERG protooncogene frequently gains hormonal control by seizing gene regulatory elements of TMPRSS2 through genomic fusion events. Although, the androgenic activation of TMPRSS2 gene has been established, little is known about other elements that may interact with TMPRSS2 promoter sequences to modulate ERG expression in TMPRSS2-ERG gene fusion context. Comparative genomic analyses of the TMPRSS2 promoter upstream sequences and pathway analyses were performed by the Genomatix Software. NKX3.1 and ERG genes expressions were evaluated by immunoblot or by quantitative Real-Time PCR (qRT-PCR) assays in response to siRNA knockdown or heterologous expression. QRT-PCR assay was used for monitoring the gene expression levels of NKX3.1-regulated genes. Transcriptional regulatory function of NKX3.1 was assessed by luciferase assay. Recruitment of NKX3.1 to its cognate elements was monitored by Chromatin Immunoprecipitation assay. Comparative analysis of the TMPRSS2 promoter upstream sequences among different species revealed the conservation of binding sites for the androgen inducible NKX3.1 tumor suppressor. Defects of NKX3.1, such as, allelic loss, haploinsufficiency, attenuated expression or decreased protein stability represent established pathways in prostate tumorigenesis. We found that NKX3.1 directly binds to TMPRSS2 upstream sequences and negatively regulates the expression of the ERG protooncogene through the TMPRSS2-ERG gene fusion. These observations imply that the frequently noted loss-of-function of NKX3.1 cooperates with the activation of TMPRSS2-ERG fusions in prostate tumorigenesis

Prognostic significance of nuclear expression of UMP-CMP kinase in triple negative breast cancer patients

DEFF Research Database (Denmark)

Liu, Ning Qing; De Marchi, Tommaso; Timmermans, Annemieke

2016-01-01

associated to its expression through gene set enrichment analysis (GSEA). A total of 461 TNBC paraffin-embedded tissues were collected from different academic hospitals in Europe, incorporated into tissue micro-arrays (TMA), and stained for CMPK1 expression. We also collected gene expression data of 60...

Strong negative self regulation of Prokaryotic transcription factors increases the intrinsic noise of protein expression

Directory of Open Access Journals (Sweden)

Jenkins Dafyd J

2008-01-01

Full Text Available Abstract Background Many prokaryotic transcription factors repress their own transcription. It is often asserted that such regulation enables a cell to homeostatically maintain protein abundance. We explore the role of negative self regulation of transcription in regulating the variability of protein abundance using a variety of stochastic modeling techniques. Results We undertake a novel analysis of a classic model for negative self regulation. We demonstrate that, with standard approximations, protein variance relative to its mean should be independent of repressor strength in a physiological range. Consequently, in that range, the coefficient of variation would increase with repressor strength. However, stochastic computer simulations demonstrate that there is a greater increase in noise associated with strong repressors than predicted by theory. The discrepancies between the mathematical analysis and computer simulations arise because with strong repressors the approximation that leads to Michaelis-Menten-like hyperbolic repression terms ceases to be valid. Because we observe that strong negative feedback increases variability and so is unlikely to be a mechanism for noise control, we suggest instead that negative feedback is evolutionarily favoured because it allows the cell to minimize mRNA usage. To test this, we used in silico evolution to demonstrate that while negative feedback can achieve only a modest improvement in protein noise reduction compared with the unregulated system, it can achieve good improvement in protein response times and very substantial improvement in reducing mRNA levels. Conclusion Strong negative self regulation of transcription may not always be a mechanism for homeostatic control of protein abundance, but instead might be evolutionarily favoured as a mechanism to limit the use of mRNA. The use of hyperbolic terms derived from quasi-steady-state approximation should also be avoided in the analysis of stochastic

Negative Knudsen force on heated microbeams

KAUST Repository

Zhu, Taishan

2011-11-18

Knudsen force acting on a heated microbeam adjacent to a cold substrate in a rarefied gas is a mechanical force created by unbalanced thermal gradients. The measured force has its direction pointing towards the side with a lower thermal gradient and its magnitude vanishes in both continuum and free-molecule limits. In our previous study, negative Knudsen forces were discovered at the high Knudsen regime before diminishing in the free-molecule limit. Such a phenomenon was, however, neither observed in experiment [A. Passian et al., Phys. Rev. Lett. 90, 124503 (2003)], nor captured in the latest numerical study [J. Nabeth et al., Phys. Rev. E 83, 066306 (2011)]. In this paper, the existence of such a negative Knudsen force is further confirmed using both numerical simulation and theoretical analysis. The asymptotic order of the Knudsen force near the collisionless limit is analyzed and the analytical expression of its leading term is provided, from which approaches for the enhancement of negative Knudsen forces are proposed. The discovered phenomenon could find its applications in novel mechanisms for pressure sensing and actuation.

Maternal Punitive Reactions to Children's Negative Emotions and Young Adult Trait Anger: Effect of Gender and Emotional Closeness.

Science.gov (United States)

Perry, Nicole B; Cavanaugh, Alyson; Dunbar, Angel; Leerkes, Esther M

The current study tested whether young adult's recollected reports of their mother's punitive reactions to their negative emotions in childhood predicted anger expression in young adulthood and whether emotional closeness weakens this association. Further, a three-way interaction was tested to examine whether emotional closeness is a stronger protective factor for young women than for young men. Results revealed a significant three-way interaction (gender X emotional closeness X maternal punitive reactions). For young men, maternal punitive reactions to negative emotions were directly associated with increased anger expressions. Maternal punitive reactions to young women's negative emotions in childhood were associated with increased anger in adulthood only when they reported low maternal emotional closeness. Findings suggest that maternal emotional closeness may serve as a buffer against the negative effects of maternal punitive reactions for women's anger expression in young adulthood.

Impairment of vocal expression of negative emotions in patients with Alzheimer's disease.

Science.gov (United States)

Han, Kyung-Hun; Zaytseva, Yuliya; Bao, Yan; Pöppel, Ernst; Chung, Sun Yong; Kim, Jong Woo; Kim, Hyun Taek

2014-01-01

Vocal expression of emotions (EE) in retrieval of events from autobiographical memory was investigated in patients in early stages of Alzheimer's disease (AD). Twenty-one AD patients and 19 controls were interviewed, and EE of the reported memories was rated by 8 independent evaluators. The AD group had lower EE of both recent and remote memory than controls, although EE in remote memories was better preserved in both groups. We observed positive correlations between EE and indicators of cognitive competence in AD patients. AD Patients are impaired in the ability to express emotions already at early stages of the disease, and EE seems to deteriorate along with the progression of cognitive impairment.

Limb clouds and dust on Mars from images obtained by the Visual Monitoring Camera (VMC) onboard Mars Express

Science.gov (United States)

Sánchez-Lavega, A.; Chen-Chen, H.; Ordoñez-Etxeberria, I.; Hueso, R.; del Río-Gaztelurrutia, T.; Garro, A.; Cardesín-Moinelo, A.; Titov, D.; Wood, S.

2018-01-01

The Visual Monitoring Camera (VMC) onboard the Mars Express (MEx) spacecraft is a simple camera aimed to monitor the release of the Beagle-2 lander on Mars Express and later used for public outreach. Here, we employ VMC as a scientific instrument to study and characterize high altitude aerosols events (dust and condensates) observed at the Martian limb. More than 21,000 images taken between 2007 and 2016 have been examined to detect and characterize elevated layers of dust in the limb, dust storms and clouds. We report a total of 18 events for which we give their main properties (areographic location, maximum altitude, limb projected size, Martian solar longitude and local time of occurrence). The top altitudes of these phenomena ranged from 40 to 85 km and their horizontal extent at the limb ranged from 120 to 2000 km. They mostly occurred at Equatorial and Tropical latitudes (between ∼30°N and 30°S) at morning and afternoon local times in the southern fall and northern winter seasons. None of them are related to the orographic clouds that typically form around volcanoes. Three of these events have been studied in detail using simultaneous images taken by the MARCI instrument onboard Mars Reconnaissance Orbiter (MRO) and studying the properties of the atmosphere using the predictions from the Mars Climate Database (MCD) General Circulation Model. This has allowed us to determine the three-dimensional structure and nature of these events, with one of them being a regional dust storm and the two others water ice clouds. Analyses based on MCD and/or MARCI images for the other cases studied indicate that the rest of the events correspond most probably to water ice clouds.

Routine sanitary radiation monitoring

International Nuclear Information System (INIS)

Marej, A.N.

1984-01-01

Hygienic bases and organization principles of radiation monitoring realized in the process of operation of nuclear power engineering enterprises are considered. The monitoring is aimed at prevention from a negative effect of ionizing radiations on public heath. It is achieved by solution of the following tasks: realization of control over radioactive waste disposal into environment, control over the level of radioactive substance content in evironmental objects, control over external and internal irradiation of population assessment of environmental radiactivity of certain regions and of the territory of the country with the subsequent informing the corresponding organizations and population

Negativity of asymmetric two-mode Gaussian states: An explicit analytic formula and physical interpretation

International Nuclear Information System (INIS)

Poon, Phoenix S. Y.; Law, C. K.

2007-01-01

We show that the negativity of a general two-mode Gaussian state can be explicitly expressed in terms of an optimal uncertainty product in position-momentum space. Such an uncertainty product is shown to have the greatest violation of a separability criterion based on positive partial transposition. Our analytic formula indicates the observables determining the negativity. For asymmetric Gaussian states, we show that the negativity is controlled by an asymmetric parameter which sets an upper bound for the negativity

Energy Monitoring

DEFF Research Database (Denmark)

Hansen, Claus T.; Madsen, Dines; Christiensen, Thomas

Energy measurement has become an important aspect of our daily lives since we have learned that energy consumption, is one of the main source of global warming. Measuring instruments varies from a simple watt-meter to more sophisticated microprocessor control devices. The negative effects...... that fossil fuels induce on our environment has forced us to research renewable energy such as sunlight, wind etc. This new environmental awareness has also helped us to realize the importance of monitoring and controlling our energy use. The main purpose in this research is to introduce a more sophisticated...... but affordable way to monitor energy consumption of individuals or groups of home appliances. By knowing their consumption the utilization can be regulated for more efficient use. A prototype system has been constructed to demonstrate our idea....

Expressive Writing as a Therapeutic Process for Drug Dependent Women

Science.gov (United States)

Meshberg-Cohen, Sarah; Svikis, Dace; McMahon, Thomas J

2013-01-01

Background Although women with Substance Use Disorders (SUD) have high rates of trauma and post-traumatic stress, many addiction programs do not offer trauma-specific treatments. One promising intervention is Pennebaker’s expressive writing, which involves daily, 20-minute writing sessions to facilitate disclosure of stressful experiences. Methods Women (N = 149) in residential treatment completed a randomized clinical trial comparing expressive writing to control writing. Repeated measures analysis of variance was used to document change in psychological and physical distress from baseline to 2-week and 1-month follow-ups. Analyses also examined immediate levels of negative affect following expressive writing. Results Expressive writing participants showed greater reductions in post-traumatic symptom severity, depression, and anxiety scores, when compared to control writing participants at the 2-week follow-up. No group differences were found at the 1-month follow-up. Safety data were encouraging; while expressive writing participants showed increased negative affect immediately after each writing session, there were no differences in pre-writing negative affect scores between conditions the following day. By the final writing session, participants were able to write about traumatic/stressful events without having a spike in negative affect. Conclusions Results suggest expressive writing may be a brief, safe, low cost, adjunct to SUD treatment that warrants further study as a strategy for addressing post-traumatic distress in substance-abusing women. PMID:24588298

Expressive writing as a therapeutic process for drug-dependent women.

Science.gov (United States)

Meshberg-Cohen, Sarah; Svikis, Dace; McMahon, Thomas J

2014-01-01

Although women with substance use disorders (SUDs) have high rates of trauma and posttraumatic stress, many addiction programs do not offer trauma-specific treatments. One promising intervention is Pennebaker's expressive writing, which involves daily, 20-minute writing sessions to facilitate disclosure of stressful experiences. Women (N = 149) in residential treatment completed a randomized clinical trial comparing expressive writing with control writing. Repeated-measures analysis of variance was used to document change in psychological and physical distress from baseline to 2-week and 1-month follow-ups. Analyses also examined immediate levels of negative affect following expressive writing. Expressive writing participants showed greater reductions in posttraumatic symptom severity, depression, and anxiety scores, when compared with control writing participants at the 2-week follow-up. No group differences were found at the 1-month follow-up. Safety data were encouraging: although expressive writing participants showed increased negative affect immediately after each writing session, there were no differences in pre-writing negative affect scores between conditions the following day. By the final writing session, participants were able to write about traumatic/stressful events without having a spike in negative affect. Results suggest that expressive writing may be a brief, safe, low-cost, adjunct to SUD treatment that warrants further study as a strategy for addressing posttraumatic distress in substance-abusing women.

Neuropsychology of reward learning and negative symptoms in schizophrenia.

Science.gov (United States)

Nestor, Paul G; Choate, Victoria; Niznikiewicz, Margaret; Levitt, James J; Shenton, Martha E; McCarley, Robert W

2014-11-01

We used the Iowa Gambling Test (IGT) to examine the relationship of reward learning to both neuropsychological functioning and symptom formation in 65 individuals with schizophrenia. Results indicated that compared to controls, participants with schizophrenia showed significantly reduced reward learning, which in turn correlated with reduced intelligence, memory and executive function, and negative symptoms. The current findings suggested that a disease-related disturbance in reward learning may underlie both cognitive and motivation deficits, as expressed by neuropsychological impairment and negative symptoms in schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.

Imbalance in leptin-adiponectin levels and leptin receptor expression as chief contributors to triple negative breast cancer progression in Northeast India.

Science.gov (United States)

Sultana, Rizwana; Kataki, Amal Ch; Borthakur, Bibhuti Bhusan; Basumatary, Tarun K; Bose, Sujoy

2017-07-20

Triple-Negative breast cancer (TNBC), accounts for a large percentage of breast cancer cases in India including Northeast India. TNBC has an unclear molecular aetiology and hence limited targeted therapies. Human breast is comprised of glandular, ductal, connective, and adipose tissues. Adipose tissue is composed of adipocytes. The adipocytes apart from being energy storage depots, are also active sources of adipocytokines and/or adipokines. The role of adipokines in breast cancer including TNBC has been sporadically documented. Two adipokines in particular, leptin and adiponectin, have come to be recognized for their influence on breast cancer risk and tumour biology. Therefore, the aim of this study was to understand the association of differential expression of critical adipokines and associated cellular mechanism in the susceptibility and severity of TNBC in northeast Indian population. We collected 68 TNBC and 63 controls cases and examined for serum leptin and adiponectin levels using enzyme linked immunosorbent assay (ELISA). Leptin Receptor (Ob-R) mRNA expression was determined by real-time polymerase chain reaction (RT-PCR) assay. Differential Ob-R mRNA expression and correlation with cancer stem cell (CSC) markers was evaluated, and correlated with severity. The serum leptin levels were significantly associated with TNBC severity, while the adiponectin levels were comparative. The serum leptin levels correlated inversely with the adiponetin levels. Serum leptin levels were unaffected with difference in parity. The difference in leptin levels in pre and post menopausal cases were found to be statistically non-significant. Higher leptin levels were also found to be associated obesity, mortality and recurrence. Obesity was found to be a factor for TNBC pathogenesis and severity. Increased Ob-R mRNA expression was associated with TNBC, significantly with TNBC severity, and was significantly higher in obese patients with higher grade TNBC cases. The Ob-R gene

Increased macroH2A1.1 expression correlates with poor survival of triple-negative breast cancer patients.

Directory of Open Access Journals (Sweden)

Anne-Claire Lavigne

Full Text Available PURPOSE: Epithelial-Mesenchymal Transition (EMT features appear to be key events in development and progression of breast cancer. Epigenetic modifications contribute to the establishment and maintenance of cancer subclasses, as well as to the EMT process. Whether histone variants contribute to these transformations is not known. We investigated the relative expression levels of histone macroH2A1 splice variants and correlated it with breast cancer status/prognosis/types. METHODS: To detect differential expression of macroH2A1 variant mRNAs in breast cancer cells and tumor samples, we used the following databases: GEO, EMBL-EBI and publisher databases (may-august 2012. We extracted macroH2A1.1/macroH2A1 mRNA ratios and performed correlation studies on intrinsic molecular subclasses of breast cancer and on molecular characteristics of EMT. Associations between molecular and survival data were determined. RESULTS: We found increased macroH2A1.1/macroH2A1 mRNA ratios to be associated with the claudin-low intrinsic subtype in breast cancer cell lines. At the molecular level this association translates into a positive correlation between macroH2A1 ratios and molecular characteristics of the EMT process. Moreover, untreated Triple Negative Breast Cancers presenting a high macroH2A1.1 mRNA ratio exhibit a poor outcome. CONCLUSION: These results provide first evidence that macroH2A1.1 could be exploited as an actor in the maintenance of a transient cellular state in EMT progress towards metastatic development of breast tumors.

Parental efficacy, parental monitoring efficacy, and monitoring among Asian-Indian parents of adolescents living in Chennai, India.

Science.gov (United States)

Ranganathan, Chitra; Montemayor, Raymond

2014-12-01

The purpose of this study was to investigate the relationship between parental efficacy and a new concept entitled parental monitoring efficacy, and to examine the association between parental monitoring efficacy and monitoring. We conducted two studies on two samples of Asian-Indian parents and adolescents living in Chennai, India. In the first study of 241 parents of adolescents in grades, 9-12, we constructed a new measure of parental efficacy that included two factors. The first factor, responding competently to negative adolescent behavior was more strongly predictive of parental monitoring efficacy than the second factor, instilling positive behavior. In the second study of 215 parents and adolescents in grades 10 and 12, parental monitoring efficacy predicted monitoring, especially adolescent disclosure and parental control. The importance of parental control as a monitoring technique among traditional Indian parents was discussed. Copyright © 2014 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

[Negative hallucination, self-onsciousness and ageing].

Science.gov (United States)

Hazif-Thomas, C; Stephan, F; Walter, M; Thomas, P

2015-04-01

Negative hallucinations are characterized by a defect in perception of an object or a person, or a denial of the existence of their perception. Negative hallucinations create blank spaces, due to both an impossible representation and an incapability of investment in reality. They have a close relationship with Cotard's syndrome, delusional theme of organ denial observed in melancholic syndromes in the elderly. Phenomenological approach. The phenomenology of negative hallucinations provides quite an amount of information on the origin of the psychotic symptoms when one is rather old. The connections between hallucinations, mood disorders and negative symptoms are often difficult to live with for the nearest and dearest. Negative hallucinations require a strict approach to identify their expression that is crucial because a wide heterogeneity exists within the pathological pictures, as in Cotard's syndrome. Although the negative hallucination has an anti traumatic function in elderly people fighting against mental pain, it still represents a deficiency in symbolization. The prevalence of this symptom is without doubt underestimated, although its presence often underlines thymic suffering that is more striking. These hallucinatory symptoms have an important impact on the patients' daily life, and they appear to be prisoners of a suffering, which cannot be revealed. We propose in this article to review the clinical symptoms of negative hallucinations in the elderly and the way to manage them. The medicinal approaches are not always effective. A greater place must be given to what is in connection with the body, aiming at a strong impact and thus to offer non-pharmacological approaches, such as somatic ones, which can be either invasive (electroconvulsive therapy) or not (transcranial magnetic stimulation). Copyright © 2014. Published by Elsevier Masson SAS.

The rules of gene expression in plants: Organ identity and gene body methylation are key factors for regulation of gene expression in Arabidopsis thaliana

Directory of Open Access Journals (Sweden)

Gutiérrez Rodrigo A

2008-09-01

Full Text Available Abstract Background Microarray technology is a widely used approach for monitoring genome-wide gene expression. For Arabidopsis, there are over 1,800 microarray hybridizations representing many different experimental conditions on Affymetrix™ ATH1 gene chips alone. This huge amount of data offers a unique opportunity to infer the principles that govern the regulation of gene expression in plants. Results We used bioinformatics methods to analyze publicly available data obtained using the ATH1 chip from Affymetrix. A total of 1887 ATH1 hybridizations were normalized and filtered to eliminate low-quality hybridizations. We classified and compared control and treatment hybridizations and determined differential gene expression. The largest differences in gene expression were observed when comparing samples obtained from different organs. On average, ten-fold more genes were differentially expressed between organs as compared to any other experimental variable. We defined "gene responsiveness" as the number of comparisons in which a gene changed its expression significantly. We defined genes with the highest and lowest responsiveness levels as hypervariable and housekeeping genes, respectively. Remarkably, housekeeping genes were best distinguished from hypervariable genes by differences in methylation status in their transcribed regions. Moreover, methylation in the transcribed region was inversely correlated (R2 = 0.8 with gene responsiveness on a genome-wide scale. We provide an example of this negative relationship using genes encoding TCA cycle enzymes, by contrasting their regulatory responsiveness to nitrate and methylation status in their transcribed regions. Conclusion Our results indicate that the Arabidopsis transcriptome is largely established during development and is comparatively stable when faced with external perturbations. We suggest a novel functional role for DNA methylation in the transcribed region as a key determinant

[Antimicrobial therapy in severe infections with multidrug-resistant Gram-negative bacterias].

Science.gov (United States)

Duszyńska, Wiesława

2010-01-01

Multidrug-resistant Gram-negative bacteria pose a serious and rapidly emerging threat to patients in healthcare settings, and are especially prevalent and problematic in intensive therapy units. Recently, the emergence of pandrug-resistance in Gram-negative bacteria poses additional concerns. This review examines the clinical impact and epidemiology of multidrug-resistant Gram-negative bacteria as a cause of increased morbidity and mortality among ITU patients. Beta-lactamases, cephalosporinases and carbapenemases play the most important role in resistance to antibiotics. Despite the tendency to increased resistance, carbapenems administered by continuous infusion remain the most effective drugs in severe sepsis. Drug concentration monitoring, albeit rarely used in practice, is necessary to ensure an effective therapeutic effect.

Appetitive Motivation and Negative Emotion Reactivity among Remitted Depressed Youth

Science.gov (United States)

Hankin, Benjamin L.; Wetter, Emily K.; Flory, Kate

2012-01-01

Depression has been characterized as involving altered appetitive motivation and emotional reactivity. Yet no study has examined objective indices of emotional reactivity when the appetitive/approach system is suppressed in response to failure to attain a self-relevant goal and desired reward. Three groups of youth (N = 98, ages 9–15; remitted depressed, n = 34; externalizing disordered without depression, n = 30, and healthy controls, n = 34) participated in a novel reward striving task designed to activate the appetitive/approach motivation system. Objective facial expressions of emotion were videotaped and coded throughout both failure (i.e., nonreward) and control (success and reward) conditions. Observational coding of facial expressions as well as youths’ subjective emotion reports showed that the remitted depressed youth specifically exhibited more negative emotional reactivity to failure in the reward striving task, but not the control condition. Neither externalizing disordered (i.e., ADHD, CD, and/ or ODD) nor control youth displayed greater negative emotional reactivity in either the failure or control condition. Findings suggest that depression among youth is related to dysregulated appetitive motivation and associated negative emotional reactivity after failing to achieve an important, self-relevant goal and not attaining reward. These deficits in reward processing appear to be specific to depression as externalizing disordered youth did not display negative emotional reactivity to failure after their appetitive motivation system was activated. PMID:22901275

Negative regulators of brown adipose tissue (BAT)-mediated thermogenesis.

Science.gov (United States)

Sharma, Bal Krishan; Patil, Mallikarjun; Satyanarayana, Ande

2014-12-01

Brown adipose tissue (BAT) is specialized for energy expenditure, a process called adaptive thermogenesis. PET-CT scans recently demonstrated the existence of metabolically active BAT in adult humans, which revitalized our interest in BAT. Increasing the amount and/or activity of BAT holds tremendous promise for the treatment of obesity and its associated diseases. PGC1α is the master regulator of UCP1-mediated thermogenesis in BAT. A number of proteins have been identified to influence thermogenesis either positively or negatively through regulating the expression or transcriptional activity of PGC1α. Therefore, BAT activation can be achieved by either inducing the expression of positive regulators of PGC1α or by inhibiting the repressors of the PGC1α/UCP1 pathway. Here, we review the most important negative regulators of PGC1α/UCP1 signaling and their mechanism of action in BAT-mediated thermogenesis. © 2014 Wiley Periodicals, Inc.

Multilevel analysis of facial expressions of emotion and script: self-report (arousal and valence) and psychophysiological correlates.

Science.gov (United States)

Balconi, Michela; Vanutelli, Maria Elide; Finocchiaro, Roberta

2014-09-26

The paper explored emotion comprehension in children with regard to facial expression of emotion. The effect of valence and arousal evaluation, of context and of psychophysiological measures was monitored. Indeed subjective evaluation of valence (positive vs. negative) and arousal (high vs. low), and contextual (facial expression vs. facial expression and script) variables were supposed to modulate the psychophysiological responses. Self-report measures (in terms of correct recognition, arousal and valence attribution) and psychophysiological correlates (facial electromyography, EMG, skin conductance response, SCR, and heart rate, HR) were observed when children (N = 26; mean age = 8.75 y; range 6-11 y) looked at six facial expressions of emotions (happiness, anger, fear, sadness, surprise, and disgust) and six emotional scripts (contextualized facial expressions). The competencies about the recognition, the evaluation on valence and arousal was tested in concomitance with psychophysiological variations. Specifically, we tested for the congruence of these multiple measures. Log-linear analysis and repeated measure ANOVAs showed different representations across the subjects, as a function of emotion. Specifically, children' recognition and attribution were well developed for some emotions (such as anger, fear, surprise and happiness), whereas some other emotions (mainly disgust and sadness) were less clearly represented. SCR, HR and EMG measures were modulated by the evaluation based on valence and arousal, with increased psychophysiological values mainly in response to anger, fear and happiness. As shown by multiple regression analysis, a significant consonance was found between self-report measures and psychophysiological behavior, mainly for emotions rated as more arousing and negative in valence. The multilevel measures were discussed at light of dimensional attribution model.

Is psychotherapy for functional somatic syndromes harmful? A mixed methods study on negative effects.

Science.gov (United States)

Holsting, A F; Pedersen, H F; Rask, M T; Frostholm, L; Schröder, A

2017-07-01

Concern for negative effects of psychotherapy for functional somatic syndromes (FSS) has been expressed by clinicians and some patient associations, which may prevent patients from seeking treatment. Therefore, we sought to explore the occurrence and characteristics of negative effects from group-based psychotherapy as experienced by patients with severe or multiple FSS. An adapted version of the explanatory sequential mixed methods design was applied. We used data from an on-going pilot study on Acceptance and Commitment Therapy and Mindfulness-Based Stress Reduction. Negative effects were measured by Inventory for the assessment of Negative Effects of Psychotherapy (INEP). In addition, telephone interviews were conducted with randomly chosen patients and patients who reported negative effects. The latter were asked to elaborate on their INEP response. Quantitative data were analysed descriptively while interview transcripts were explored by thematic analysis. Eighty patients responded to the questionnaire (89%). Negative effects to different extent (from 'slightly agree' to 'fully agree') were reported by 25 (31%). The most frequent negative effects were dependence on the therapist (12%), feeling down after therapy (6%) and insurance problems (7%). By exploring 27 participants' experiences of negative effects 3 main themes were identified: relations in therapy, outcome and transition from therapy to everyday life. Patients with FSS reported a few specific negative effects, all with low frequency. Generally, therapy was well-received. Some patients did however express negative effects both within and outside the therapeutic context. It is important to inform patients about potential negative effects prior to psychotherapy. Copyright © 2017 Elsevier Inc. All rights reserved.

The costs and benefits of self-monitoring for higher functioning children and adolescents with autism.

Science.gov (United States)

Henderson, Heather A; Ono, Kim E; McMahon, Camilla M; Schwartz, Caley B; Usher, Lauren V; Mundy, Peter C

2015-02-01

The ability to regulate behaviors and emotions depends in part on the ability to flexibly monitor one's own progress toward a goal. Atypical patterns of response monitoring have been reported in individuals with autism spectrum disorders (ASD). In the current study we examined the error related negativity (ERN), an electrophysiological index of response monitoring, in relation to behavioral, social cognitive, and emotional presentation in higher functioning children (8-16 years) diagnosed with autism (HFA: N = 38) and an age- and IQ-matched sample of children without autism (COM: N = 36). Both HFA and COM participants displayed larger amplitude responses to error compared to correct response trials and these amplitudes did not differ by diagnostic group. For participants with HFA, larger ERN amplitudes were associated with more parent-reported autistic symptoms and more self-reported internalizing problems. However, across the full sample, larger ERN amplitudes were associated with better performance on theory of mind tasks. The results are discussed in terms of the utility of electrophysiological measures for understanding essential moderating processes that contribute to the spectrum of behavioral expression in the development of ASD.

Comprehension of Action Negation Involves Inhibitory Simulation

Directory of Open Access Journals (Sweden)

Francesco eForoni

2013-05-01

Full Text Available Previous research suggests that action language is comprehended by activating the motor system. We report a study, investigating a critical question in this research field: Do negative sentences activate the motor system? Participants were exposed to sentences in the affirmation and negation forms while the zygomatic muscle activity on the left side of the face was continuously measured (Electromyography technique: EMG. Sentences were descriptions of emotional expressions that mapped either directly upon the zygomatic muscle (e.g., ‘I am smiling’ or did not (e.g., ‘I am frowning’. Reading sentences involving the negation of the activity of a specific muscle (zygomatic major - I am not smiling is shown to lead to the inhibition of this muscle. Reading sentences involving the affirmative form instead (I am smiling leads to the activation of zygomatic mucle. In contrast, sentences describing an activity that is irrelevant to the zygomatic muscle (e.g., ‘I am frowning’ or ‘I am not frowning’ produce no muscle activity. These results extend the range of simulation models to negation and by implication to an abstract domain. We discuss how this research contributes to the grounding of abstract and concrete concepts.

The modulating effect of personality traits on neural error monitoring: evidence from event-related FMRI.

Science.gov (United States)

Sosic-Vasic, Zrinka; Ulrich, Martin; Ruchsow, Martin; Vasic, Nenad; Grön, Georg

2012-01-01

The present study investigated the association between traits of the Five Factor Model of Personality (Neuroticism, Extraversion, Openness for Experiences, Agreeableness, and Conscientiousness) and neural correlates of error monitoring obtained from a combined Eriksen-Flanker-Go/NoGo task during event-related functional magnetic resonance imaging in 27 healthy subjects. Individual expressions of personality traits were measured using the NEO-PI-R questionnaire. Conscientiousness correlated positively with error signaling in the left inferior frontal gyrus and adjacent anterior insula (IFG/aI). A second strong positive correlation was observed in the anterior cingulate gyrus (ACC). Neuroticism was negatively correlated with error signaling in the inferior frontal cortex possibly reflecting the negative inter-correlation between both scales observed on the behavioral level. Under present statistical thresholds no significant results were obtained for remaining scales. Aligning the personality trait of Conscientiousness with task accomplishment striving behavior the correlation in the left IFG/aI possibly reflects an inter-individually different involvement whenever task-set related memory representations are violated by the occurrence of errors. The strong correlations in the ACC may indicate that more conscientious subjects were stronger affected by these violations of a given task-set expressed by individually different, negatively valenced signals conveyed by the ACC upon occurrence of an error. Present results illustrate that for predicting individual responses to errors underlying personality traits should be taken into account and also lend external validity to the personality trait approach suggesting that personality constructs do reflect more than mere descriptive taxonomies.

The modulating effect of personality traits on neural error monitoring: evidence from event-related FMRI.

Directory of Open Access Journals (Sweden)

Zrinka Sosic-Vasic

Full Text Available The present study investigated the association between traits of the Five Factor Model of Personality (Neuroticism, Extraversion, Openness for Experiences, Agreeableness, and Conscientiousness and neural correlates of error monitoring obtained from a combined Eriksen-Flanker-Go/NoGo task during event-related functional magnetic resonance imaging in 27 healthy subjects. Individual expressions of personality traits were measured using the NEO-PI-R questionnaire. Conscientiousness correlated positively with error signaling in the left inferior frontal gyrus and adjacent anterior insula (IFG/aI. A second strong positive correlation was observed in the anterior cingulate gyrus (ACC. Neuroticism was negatively correlated with error signaling in the inferior frontal cortex possibly reflecting the negative inter-correlation between both scales observed on the behavioral level. Under present statistical thresholds no significant results were obtained for remaining scales. Aligning the personality trait of Conscientiousness with task accomplishment striving behavior the correlation in the left IFG/aI possibly reflects an inter-individually different involvement whenever task-set related memory representations are violated by the occurrence of errors. The strong correlations in the ACC may indicate that more conscientious subjects were stronger affected by these violations of a given task-set expressed by individually different, negatively valenced signals conveyed by the ACC upon occurrence of an error. Present results illustrate that for predicting individual responses to errors underlying personality traits should be taken into account and also lend external validity to the personality trait approach suggesting that personality constructs do reflect more than mere descriptive taxonomies.

Ambivalence, prejudice and negative behavioural tendencies towards out-groups: The moderating role of attitude basis.

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Costarelli, Sandro; Gerłowska, Justyna

2015-01-01

Two experiments explored the relations between prejudice (suppression), (cognitive) ambivalence and negative behavioural tendencies towards out-groups. The current work argues that expressing out-group ambivalence based on cognitive, but not affective, information is a strategy to justify one's otherwise suppressed prejudice, which may ultimately "cover" the discriminatory nature of out-group-directed negative behavioural tendencies. Two experiments show that (1) participants evaluating the out-group in a normative context inducing prejudice suppression are more likely to self-report ambivalent beliefs rather than ambivalent emotions concerning the out-group as compared with participants whose prejudice expression is induced and (2) high-prejudice participants compared with low-prejudice participants are more prone to out-group-directed negative behavioural tendencies when these latter are self-reported after the expression of ambivalent beliefs but not ambivalent emotions concerning the out-group, and when the expression of their prejudicial evaluations is salient but not when it is not. In light of the extent to which ambivalent attitudes towards out-groups are often seamlessly integrated into public discourse, the implications of the findings are discussed not only for intergroup research but also at the societal level.

Program of environmental radiological monitoring

International Nuclear Information System (INIS)

2005-11-01

This Regulation refers to the requirement of the Regulation CNEN-NN.3.01, 'Basic Act of Radiological Protection', as expressed in the section 5.14, related to the Program of Environmental Radiological Monitoring (PMRA)

A Gene Expression Classifier of Node-Positive Colorectal Cancer

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Paul F. Meeh

2009-10-01

Full Text Available We used digital long serial analysis of gene expression to discover gene expression differences between node-negative and node-positive colorectal tumors and developed a multigene classifier able to discriminate between these two tumor types. We prepared and sequenced long serial analysis of gene expression libraries from one node-negative and one node-positive colorectal tumor, sequenced to a depth of 26,060 unique tags, and identified 262 tags significantly differentially expressed between these two tumors (P < 2 x 10-6. We confirmed the tag-to-gene assignments and differential expression of 31 genes by quantitative real-time polymerase chain reaction, 12 of which were elevated in the node-positive tumor. We analyzed the expression levels of these 12 upregulated genes in a validation panel of 23 additional tumors and developed an optimized seven-gene logistic regression classifier. The classifier discriminated between node-negative and node-positive tumors with 86% sensitivity and 80% specificity. Receiver operating characteristic analysis of the classifier revealed an area under the curve of 0.86. Experimental manipulation of the function of one classification gene, Fibronectin, caused profound effects on invasion and migration of colorectal cancer cells in vitro. These results suggest that the development of node-positive colorectal cancer occurs in part through elevated epithelial FN1 expression and suggest novel strategies for the diagnosis and treatment of advanced disease.

Do you remember your sad face? The roles of negative cognitive style and sad mood.

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Caudek, Corrado; Monni, Alessandra

2013-01-01

We studied the effects of negative cognitive style, sad mood, and facial affect on the self-face advantage in a sample of 66 healthy individuals (mean age 26.5 years, range 19-47 years). The sample was subdivided into four groups according to inferential style and responsivity to sad mood induction. Following a sad mood induction, we examined the effect on working memory of an incidental association between facial affect, facial identity, and head-pose orientation. Overall, head-pose recognition was more accurate for the self-face than for nonself face (self-face advantage, SFA). However, participants high in negative cognitive style who experienced higher levels of sadness displayed a stronger SFA for sad expressions than happy expressions. The remaining participants displayed an opposite bias (a stronger SFA for happy expressions than sad expressions), or no bias. These findings highlight the importance of trait-vulnerability status in the working memory biases related to emotional facial expressions.

Negative emotions boost user activity at BBC forum

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Chmiel, Anna; Sobkowicz, Pawel; Sienkiewicz, Julian; Paltoglou, Georgios; Buckley, Kevan; Thelwall, Mike; Hołyst, Janusz A.

2011-08-01

We present an empirical study of user activity in online BBC discussion forums, measured by the number of posts written by individual debaters and the average sentiment of these posts. Nearly 2.5 million posts from over 18 thousand users were investigated. Scale-free distributions were observed for activity in individual discussion threads as well as for overall activity. The number of unique users in a thread normalized by the thread length decays with thread length, suggesting that thread life is sustained by mutual discussions rather than by independent comments. Automatic sentiment analysis shows that most posts contain negative emotions and the most active users in individual threads express predominantly negative sentiments. It follows that the average emotion of longer threads is more negative and that threads can be sustained by negative comments. An agent-based computer simulation model has been used to reproduce several essential characteristics of the analyzed system. The model stresses the role of discussions between users, especially emotionally laden quarrels between supporters of opposite opinions, and represents many observed statistics of the forum.

Staff acceptance of video monitoring for coordination: a video system to support perioperative situation awareness.

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Kim, Young Ju; Xiao, Yan; Hu, Peter; Dutton, Richard

2009-08-01

To understand staff acceptance of a remote video monitoring system for operating room (OR) coordination. Improved real-time remote visual access to OR may enhance situational awareness but also raises privacy concerns for patients and staff. Survey. A system was implemented in a six-room surgical suite to display OR monitoring video at an access restricted control desk area. Image quality was manipulated to improve staff acceptance. Two months after installation, interviews and a survey were conducted on staff acceptance of video monitoring. About half of all OR personnel responded (n = 63). Overall levels of concerns were low, with 53% rated no concerns and 42% little concern. Top two reported uses of the video were to see if cases are finished and to see if a room is ready. Viewing the video monitoring system as useful did not reduce levels of concern. Staff in supervisory positions perceived less concern about the system's impact on privacy than did those supervised (p < 0.03). Concerns for patient privacy correlated with concerns for staff privacy and performance monitoring. Technical means such as manipulating image quality helped staff acceptance. Manipulation of image quality resulted overall acceptance of monitoring video, with residual levels of concerns. OR nurses may express staff privacy concern in the form of concerns over patient privacy. This study provided suggestions for technological and implementation strategies of video monitoring for coordination use in OR. Deployment of communication technology and integration of clinical information will likely raise concerns over staff privacy and performance monitoring. The potential gain of increased information access may be offset by negative impact of a sense of loss of autonomy.

Programmed Death Ligand 1 (PD-L1 Tumor Expression Is Associated with a Better Prognosis and Diabetic Disease in Triple Negative Breast Cancer Patients

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Gerardo Botti

2017-02-01

Full Text Available Triple Negative Breast Cancers (TNBC subtype is an aggressive disease with poor clinical outcome. The only treatment available is surgery followed by chemotherapy or radiotherapy. Programmed death-ligand 1 (PD-L1 is a trans-membrane protein expressed on a wide variety of cells including immune cells, epithelial and vascular endothelial cells. Recently, PD-1/PD-L1 pathway signaling was described as an adaptive immune resistance mechanism enacted by the tumor cells to evade the immune response. Its presence on tumor cell membranes, acquired for this reason, through time, is an important prognostic value. However, data available in the literature about PD-L1 immunohistochemical expression in breast cancer are often discordant and not uniform, probably for the use of different antibodies clones and the high molecular heterogeneity of the different tumor types. The absence of target therapies, in particular for TNBC, has shifted the clinical attention mainly on the role of PD-L1 in this subtype of breast cancer. In this study, we evaluated tumor and TIL (tumor infiltrating lymphocytes PDL-1 expression in a series of TNBC, included in Tissue Micro Arrays (TMAs, to define its real prognostic value, optimizing immunohistochemistry method with an “approved for diagnostic assay” antibody. PD-L1 expression directly correlated with proliferation index (Ki-67, glycemia, the presence of diabetes and indirectly with menopausal status, presence of lymph node metastasis and relapse. The analysis of Kaplan–Meier showed that an increased PD-L1 expression was strongly associated with better disease-free survival (DFS but not correlated with overall survival (OS. Our data confirmed that PD-L1 could be an important marker for prognostic stratification and for planning immune checkpoint inhibitors therapies in patients with TNBC.

A structural equation model of the relationship between insomnia, negative affect, and paranoid thinking.

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Alexander J Scott

Full Text Available A growing body of evidence points to relationships between insomnia, negative affect, and paranoid thinking. However, studies are needed to examine (i whether negative affect mediates the relation between insomnia and paranoid thinking, (ii whether different types of insomnia exert different effects on paranoia, and (iii to compare the impact of objective and self-reported sleeping difficulties.Structural equation modelling was therefore used to test competing models of the relationships between self-reported insomnia, negative affect, and paranoia. n = 348 participants completed measures of insomnia, negative affect and paranoia. A subset of these participants (n = 91 went on to monitor their sleep objectively (using a portable sleep monitor made by Zeo for seven consecutive nights. Associations between objectively recorded sleep, negative affect, and paranoia were explored using linear regression.The findings supported a fully mediated model where self-reported delayed sleep onset, but not self-reported problems with sleep maintenance or objective measures of sleep, was directly associated with negative affect that, in turn, was associated with paranoia. There was no evidence of a direct association between delayed sleep onset or sleep maintenance problems and paranoia.Taken together, the findings point to an association between perceived (but not objective difficulties initially falling asleep (but not maintaining sleep and paranoid thinking; a relationship that is fully mediated by negative affect. Future research should seek to disentangle the causal relationships between sleep, negative affect, and paranoia (e.g., by examining the effect of an intervention using prospective designs that incorporate experience sampling. Indeed, interventions might profitably target (i perceived sleep quality, (ii sleep onset, and / or (iii emotion regulation as a route to reducing negative affect and, thus, paranoid thinking.

Wolbachia-induced aae-miR-12 miRNA negatively regulates the expression of MCT1 and MCM6 genes in Wolbachia-infected mosquito cell line.

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Solomon Osei-Amo

Full Text Available BACKGROUND: Best recognized for its role in manipulating host reproduction, the parasitic gram-negative Wolbachia pipientis is known to colonize a wide range of invertebrates. The endosymbiotic bacterium has recently been shown to cause a life-shortening effect as well as inhibiting replication of arboviruses in Aedes aegypti; although the molecular mechanisms behind these effects are largely unknown. MicroRNAs (miRNAs have been determined to have a wide range of roles in regulating gene expression in eukaryotes. A recent study showed that several A. aegypti mosquito miRNAs are differentially expressed when infected with Wolbachia. METHODOLOGY/PRINCIPAL FINDINGS: Based on the prior knowledge that one of these miRNAs, aae-miR-12, is differentially expressed in mosquitoes infected with Wolbachia, we aimed to determine any significance of this mediation. We also set out to characterize the target genes of this miRNA in the A. aegpyti genome. Bioinformatic approaches predicted a list of potential target genes and subsequent functional analyses confirmed that two of these, DNA replication licensing (MCM6 and monocarboxylate transporter (MCT1, are under the regulative control of aae-miR-12. We also demonstrated that aae-miR-12 is critical in the persistence of Wolbachia in the host cell. CONCLUSIONS/SIGNIFICANCE: Our study has identified two target genes of aae-miR-12, a differentially expressed mosquito miRNA in Wolbachia-infected cells, and determined that the miRNA affects Wolbachia density in the host cells.

Exposure to Parents' Negative Emotions as a Developmental Pathway to the Family Aggregation of Depression and Anxiety in the First Year of Life.

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Aktar, Evin; Bögels, Susan M

2017-12-01

Depression and anxiety load in families. In the present study, we focus on exposure to parental negative emotions in first postnatal year as a developmental pathway to early parent-to-child transmission of depression and anxiety. We provide an overview of the little research available on the links between infants' exposure to negative emotion and infants' emotional development in this developmentally sensitive period, and highlight priorities for future research. To address continuity between normative and maladaptive development, we discuss exposure to parental negative emotions in infants of parents with as well as without depression and/or anxiety diagnoses. We focus on infants' emotional expressions in everyday parent-infant interactions, and on infants' attention to negative facial expressions as early indices of emotional development. Available evidence suggests that infants' emotional expressions echo parents' expressions and reactions in everyday interactions. In turn, infants exposed more to negative emotions from the parent seem to attend less to negative emotions in others' facial expressions. The links between exposure to parental negative emotion and development hold similarly in infants of parents with and without depression and/or anxiety diagnoses. Given its potential links to infants' emotional development, and to later psychological outcomes in children of parents with depression and anxiety, we conclude that early exposure to parental negative emotions is an important developmental mechanism that awaits further research. Longitudinal designs that incorporate the study of early exposure to parents' negative emotion, socio-emotional development in infancy, and later psychological functioning while considering other genetic and biological vulnerabilities should be prioritized in future research.

Relationships between maternal emotional expressiveness and children's sensitivity to teacher criticism.

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Mizokawa, Ai

2013-01-01

Caregivers' emotional responses to children influence children's social and emotional development. This study investigated the association between maternal emotional expressiveness in the context of mother-child interactions and young children's sensitivity to teacher criticism. Sensitivity to teacher criticism was assessed among 53 Japanese preschoolers using hypothetical scenarios in which a puppet child representing the participant made a small error, and a puppet teacher pointed out the error. Self-report questionnaires were used to measure maternal expressiveness. The results demonstrated that negative maternal expressiveness toward one's own children was positively related to children's ratings of their own ability and negatively related to children's motivation to continue with the task after teacher criticism. Positive maternal expressiveness was not related to children's sensitivity to criticism. These findings suggest that children who have experienced more negative emotion from mothers may be more likely to hold negative beliefs about how others will respond to their behavior more generally. This may, in turn, lead to a defensively positive view of one's own abilities and a disinclination to persevere as protection from additional opportunities for teacher evaluation.

Epigenetic-based combinatorial resveratrol and pterostilbene alters DNA damage response by affecting SIRT1 and DNMT enzyme expression, including SIRT1-dependent γ-H2AX and telomerase regulation in triple-negative breast cancer

International Nuclear Information System (INIS)

Kala, Rishabh; Shah, Harsh N.; Martin, Samantha L.; Tollefsbol, Trygve O.

2015-01-01

Nutrition is believed to be a primary contributor in regulating gene expression by affecting epigenetic pathways such as DNA methylation and histone modification. Resveratrol and pterostilbene are phytoalexins produced by plants as part of their defense system. These two bioactive compounds when used alone have been shown to alter genetic and epigenetic profiles of tumor cells, but the concentrations employed in various studies often far exceed physiologically achievable doses. Triple-negative breast cancer (TNBC) is an often fatal condition that may be prevented or treated through novel dietary-based approaches. HCC1806 and MDA-MB-157 breast cancer cells were used as TNBC cell lines in this study. MCF10A cells were used as control breast epithelial cells to determine the safety of this dietary regimen. CompuSyn software was used to determine the combination index (CI) for drug combinations. Combinatorial resveratrol and pterostilbene administered at close to physiologically relevant doses resulted in synergistic (CI <1) growth inhibition of TNBCs. SIRT1, a type III histone deacetylase (HDAC), was down-regulated in response to this combinatorial treatment. We further explored the effects of this novel combinatorial approach on DNA damage response by monitoring γ-H2AX and telomerase expression. With combination of these two compounds there was a significant decrease in these two proteins which might further resulted in significant growth inhibition, apoptosis and cell cycle arrest in HCC1806 and MDA-MB-157 breast cancer cells, while there was no significant effect on cellular viability, colony forming potential, morphology or apoptosis in control MCF10A breast epithelial cells. SIRT1 knockdown reproduced the effects of combinatorial resveratrol and pterostilbene-induced SIRT1 down-regulation through inhibition of both telomerase activity and γ-H2AX expression in HCC1806 breast cancer cells. As a part of the repair mechanisms and role of SIRT1 in recruiting DNMTs

Identification and prognostic value of anterior gradient protein 2 expression in breast cancer based on tissue microarray.

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Guo, Jilong; Gong, Guohua; Zhang, Bin

2017-07-01

Breast cancer has attracted substantial attention as one of the major cancers causing death in women. It is crucial to find potential biomarkers of prognostic value in breast cancer. In this study, the expression pattern of anterior gradient protein 2 in breast cancer was identified based on the main molecular subgroups. Through analysis of 69 samples from the Gene Expression Omnibus database, we found that anterior gradient protein 2 expression was significantly higher in non-triple-negative breast cancer tissues compared with normal tissues and triple-negative breast cancer tissues (p gradient protein 2 expression pattern. Furthermore, we performed immunohistochemical analysis. The quantification results revealed that anterior gradient protein 2 is highly expressed in non-triple-negative breast cancer (grade 3 excluded) and grade 1 + 2 (triple-negative breast cancer excluded) tumours compared with normal tissues. Anterior gradient protein 2 was significantly highly expressed in non-triple-negative breast cancer (grade 3 excluded) and non-triple-negative breast cancer tissues compared with triple-negative breast cancer tissues (p gradient protein 2 was significantly highly expressed in grade 1 + 2 (triple-negative breast cancer excluded) and grade 1 + 2 tissues compared with grade 3 tissues (p gradient protein 2 expression was significantly associated with histologic type, histological grade, oestrogen status and progesterone status. Univariate analysis of clinicopathological variables showed that anterior gradient protein 2 expression, tumour size and lymph node status were significantly correlated with overall survival in patients with grade 1 and 2 tumours. Cox multivariate analysis revealed anterior gradient protein 2 as a putative independent indicator of unfavourable outcomes (p = 0.031). All these data clearly showed that anterior gradient protein 2 is highly expressed in breast cancer and can be regarded as a putative biomarker for

Clinicopathologic Characteristics of Oestrogen Receptor-Positive/Progesterone Receptor-Negative/Her2-Negative Breast Cancer According to a Novel Definition of Negative Progesterone Receptor Status: A Large Population-Based Study from China.

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An-qi Li

Full Text Available A lack of progesterone receptor (PgR expression in oestrogen receptor-positive (ER+ tumours is associated with worse survival. PgR status is usually defined as positive or negative using 1% positive nuclei as a cut-off point. In this study, we aimed to assess the clinicopathologic characteristics of ER+/PgR-/HER2- tumours by comparing them with ER+/PgR+/HER2- tumours using a PgR cut-off point of 20% as a divisive criterion.We analysed 1,522 patients with primary breast cancer who had undergone surgery at the Cancer Center of Fudan University between 2012 and 2014. Age, grade, tumour size, lymph node status and lymphovascular invasion were assessed. Multinomial logistic regression, linear regression and chi-square test models were applied to assess associations between ER, PR and clinical features.ER+/PgR-/HER2- tumours showed poorer clinicopathologic characteristics relative to ER+/PgR+/HER2- tumours using a PgR threshold of 20% instead of 1%. The clinicopathologic characteristics did not differ between tumours with purely negative PgR expression and tumours with a PgR percentage ranging from 1% to 19%. The prognostic significance of PR expression appeared more pronounced in patients under a high Ki-67 status than those under a low Ki-67 status.Based on these findings, we propose the use of a novel threshold of 20% to define PgR status. Nevertheless, the impact of this new criterion on patient management and clinical treatment requires additional study.

Impact of sleep quality on amygdala reactivity, negative affect, and perceived stress.

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Prather, Aric A; Bogdan, Ryan; Hariri, Ahmad R

2013-05-01

Research demonstrates a negative impact of sleep disturbance on mood and affect; however, the biological mechanisms mediating these links are poorly understood. Amygdala reactivity to negative stimuli has emerged as one potential pathway. Here, we investigate the influence of self-reported sleep quality on associations between threat-related amygdala reactivity and measures of negative affect and perceived stress. Analyses on data from 299 participants (125 men, 50.5% white, mean [standard deviation] age = 19.6 [1.3] years) who completed the Duke Neurogenetics Study were conducted. Participants completed several self-report measures of negative affect and perceived stress. Threat-related (i.e., angry and fearful facial expressions) amygdala reactivity was assayed using blood oxygen level-dependent functional magnetic resonance imaging. Global sleep quality was assessed using the Pittsburgh Sleep Quality Index. Amygdala reactivity to fearful facial expressions predicted greater depressive symptoms and higher perceived stress in poor (β values = 0.18-1.86, p values .05). In sex-specific analyses, men reporting poorer global sleep quality showed a significant association between amygdala reactivity and levels of depression and perceived stress (β values = 0.29-0.44, p values sleep quality or in women, irrespective of sleep quality. This study provides novel evidence that self-reported sleep quality moderates the relationships between amygdala reactivity, negative affect, and perceived stress, particularly among men.

Measuring positive and negative affect in the voiced sounds of African elephants (Loxodonta africana).

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Soltis, Joseph; Blowers, Tracy E; Savage, Anne

2011-02-01

As in other mammals, there is evidence that the African elephant voice reflects affect intensity, but it is less clear if positive and negative affective states are differentially reflected in the voice. An acoustic comparison was made between African elephant "rumble" vocalizations produced in negative social contexts (dominance interactions), neutral social contexts (minimal social activity), and positive social contexts (affiliative interactions) by four adult females housed at Disney's Animal Kingdom®. Rumbles produced in the negative social context exhibited higher and more variable fundamental frequencies (F(0)) and amplitudes, longer durations, increased voice roughness, and higher first formant locations (F1), compared to the neutral social context. Rumbles produced in the positive social context exhibited similar shifts in most variables (F(0 )variation, amplitude, amplitude variation, duration, and F1), but the magnitude of response was generally less than that observed in the negative context. Voice roughness and F(0) observed in the positive social context remained similar to that observed in the neutral context. These results are most consistent with the vocal expression of affect intensity, in which the negative social context elicited higher intensity levels than the positive context, but differential vocal expression of positive and negative affect cannot be ruled out.

A Two-Factor Model Better Explains Heterogeneity in Negative Symptoms: Evidence from the Positive and Negative Syndrome Scale.

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Jang, Seon-Kyeong; Choi, Hye-Im; Park, Soohyun; Jaekal, Eunju; Lee, Ga-Young; Cho, Young Il; Choi, Kee-Hong

2016-01-01

Acknowledging separable factors underlying negative symptoms may lead to better understanding and treatment of negative symptoms in individuals with schizophrenia. The current study aimed to test whether the negative symptoms factor (NSF) of the Positive and Negative Syndrome Scale (PANSS) would be better represented by expressive and experiential deficit factors, rather than by a single factor model, using confirmatory factor analysis (CFA). Two hundred and twenty individuals with schizophrenia spectrum disorders completed the PANSS; subsamples additionally completed the Brief Negative Symptom Scale (BNSS) and the Motivation and Pleasure Scale-Self-Report (MAP-SR). CFA results indicated that the two-factor model fit the data better than the one-factor model; however, latent variables were closely correlated. The two-factor model's fit was significantly improved by accounting for correlated residuals between N2 (emotional withdrawal) and N6 (lack of spontaneity and flow of conversation), and between N4 (passive social withdrawal) and G16 (active social avoidance), possibly reflecting common method variance. The two NSF factors exhibited differential patterns of correlation with subdomains of the BNSS and MAP-SR. These results suggest that the PANSS NSF would be better represented by a two-factor model than by a single-factor one, and support the two-factor model's adequate criterion-related validity. Common method variance among several items may be a potential source of measurement error under a two-factor model of the PANSS NSF.

The direct effect of Focal Adhesion Kinase (FAK, dominant-negative FAK, FAK-CD and FAK siRNA on gene expression and human MCF-7 breast cancer cell tumorigenesis

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Zhang Li

2009-08-01

Full Text Available Abstract Background Focal adhesion kinase (FAK is a non-receptor tyrosine kinase that plays an important role in survival signaling. FAK has been shown to be overexpressed in breast cancer tumors at early stages of tumorigenesis. Methods To study the direct effect of FAK on breast tumorigenesis, we developed Tet-ON (tetracycline-inducible system of MCF-7 breast cancer cells stably transfected with FAK or dominant-negative, C-terminal domain of FAK (FAK-CD, and also FAKsiRNA with silenced FAK MCF-7 stable cell line. Increased expression of FAK in isogenic Tet-inducible MCF-7 cells caused increased cell growth, adhesion and soft agar colony formation in vitro, while expression of dominant-negative FAK inhibitor caused inhibition of these cellular processes. To study the role of induced FAK and FAK-CD in vivo, we inoculated these Tet-inducible cells in nude mice to generate tumors in the presence or absence of doxycycline in the drinking water. FAKsiRNA-MCF-7 cells were also injected into nude mice to generate xenograft tumors. Results Induction of FAK resulted in significant increased tumorigenesis, while induced FAK-CD resulted in decreased tumorigenesis. Taq Man Low Density Array assay demonstrated specific induction of FAKmRNA in MCF-7-Tet-ON-FAK cells. DMP1, encoding cyclin D binding myb-like protein 1 was one of the genes specifically affected by Tet-inducible FAK or FAK-CD in breast xenograft tumors. In addition, silencing of FAK in MCF-7 cells with FAK siRNA caused increased cell rounding, decreased cell viability in vitro and inhibited tumorigenesis in vivo. Importantly, Affymetrix microarray gene profiling analysis using Human Genome U133A GeneChips revealed >4300 genes, known to be involved in apoptosis, cell cycle, and adhesion that were significantly down- or up-regulated (p Conclusion Thus, these data for the first time demonstrate the direct effect of FAK expression and function on MCF-7 breast cancer tumorigenesis in vivo and reveal

Monitoring of railway bridges in Japan

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Abe, Makoto; Komon, Kazuki; Narumoto, Asao; Sugidate, Masao; Mori, Takeshi; Miki, Chitoshi

2000-06-01

In Japan, some monitoring systems have been introduced to evaluate conditions of the railway structures. In this work, we introduce the monitoring systems of railway bridges. Here, for example, we show the abstraction of fatigue damage monitoring system. The crack propagation properties of a side notched SUS304 thin sheet, which is affixed to a fatigue test specimen, is studied to develop a fatigue damage monitoring sensor. When cyclic loads are applied to the fatigue specimen, the side notched thin sheet behaves as a displacement controlled condition. The stress intensity factor (Delta) K is expressed by the following equation; (Delta) K equals (Delta) (sigma) (root)GL/2 where GL is the gauge length of the thin sheet. The thin sheet is fatigue pre-cracked, stress- relieved and affixed to a specimen. The results of fatigue crack propagation tests show that the crack propagation rate is dependent on stress range and gauge length, but not on crack length. Under sufficient mean stress conditions, the fatigue crack propagation rate is well expressed by a power low of (Delta) K even at such a low stress range as 20 MPa. Fatigue damage accumulated during a monitoring period can be estimated from crack propagation during the period. The sensitivity of the sensor is controlled through the gauge length of the sensor.

Two subdomains of negative symptoms in psychotic disorders: established and confirmed in two large cohorts

NARCIS (Netherlands)

Liemburg, Edith; Castelein, Stynke; Stewart, Roy; van der Gaag, Mark; Aleman, André; Knegtering, Henderikus; Kahn, René S.; Linszen, Don H.; van Os, Jim; Wiersma, Durk; Bruggeman, Richard; Cahn, Wiepke; de Haan, Lieuwe; Krabbendam, Lydia; Myin-Germeys, Inez

2013-01-01

Negative symptoms of schizophrenia are normally grouped into a single category. However, the diversity of such symptoms suggests that they are actually made up of more than one dimension. The DSM-V proposes two negative symptom domains, namely expressive deficits and avolition/asociality. We

Two subdomains of negative symptoms in psychotic disorders : Established and confirmed in two large cohorts

NARCIS (Netherlands)

Liemburg, E.; Castelein, S.; Stewart, R.; van der Gaag, M.; Aleman, A.; Knegtering, H.

Negative symptoms of schizophrenia are normally grouped into a single category. However, the diversity of such symptoms suggests that they are actually made up of more than one dimension. The DSM-V proposes two negative symptom domains, namely expressive deficits and avolition/asociality. We

Facial expressions of emotion and the course of conjugal bereavement.

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Bonanno, G A; Keltner, D

1997-02-01

The common assumption that emotional expression mediates the course of bereavement is tested. Competing hypotheses about the direction of mediation were formulated from the grief work and social-functional accounts of emotional expression. Facial expressions of emotion in conjugally bereaved adults were coded at 6 months post-loss as they described their relationship with the deceased; grief and perceived health were measured at 6, 14, and 25 months. Facial expressions of negative emotion, in particular anger, predicted increased grief at 14 months and poorer perceived health through 25 months. Facial expressions of positive emotion predicted decreased grief through 25 months and a positive but nonsignificant relation to perceived health. Predictive relations between negative and positive emotional expression persisted when initial levels of self-reported emotion, grief, and health were statistically controlled, demonstrating the mediating role of facial expressions of emotion in adjustment to conjugal loss. Theoretical and clinical implications are discussed.

Negative emotions in cancer care: do oncologists' responses depend on severity and type of emotion?

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Kennifer, Sarah L; Alexander, Stewart C; Pollak, Kathryn I; Jeffreys, Amy S; Olsen, Maren K; Rodriguez, Keri L; Arnold, Robert M; Tulsky, James A

2009-07-01

To examine how type and severity of patients' negative emotions influence oncologists' responses and subsequent conversations. We analyzed 264 audio-recorded conversations between advanced cancer patients and their oncologists. Conversations were coded for patients' expressions of negative emotion, which were categorized by type of emotion and severity. Oncologists' responses were coded as using either empathic language or blocking and distancing approaches. Patients presented fear more often than anger or sadness; severity of disclosures was most often moderate. Oncologists responded to 35% of these negative emotional disclosures with empathic language. They were most empathic when patients presented intense emotions. Responding empathically to patients' emotional disclosures lengthened discussions by an average of only 21s. Greater response rates to severe emotions suggest oncologists may recognize negative emotions better when patients express them more intensely. Oncologists were least responsive to patient fear and responded with greatest empathy to sadness. Oncologists may benefit from additional training to recognize negative emotions, even when displayed without intensity. Teaching cancer patients to better articulate their emotional concerns may also enhance patient-oncologist communication.

Conditional expression of the dominant-negative TGF-β receptor type II elicits lingual epithelial hyperplasia in transgenic mice.

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Li, Feng; Zhou, Mingliang

2013-05-01

The transforming growth factor-β (TGF-β) signaling pathway is generally believed to be a potent inhibitor of proliferation. However, many epithelia lacking the essential Tgfbr2 gene still maintain normal tissue homeostasis. Here, transgenic mice expressing rtTA from the human keratin 14 (K14) promoter were used to generate an inducible dominant-negative TGF-β receptor type II (Tgfbr2) mutant model, which allowed us to distinguish between the primary and secondary effects of TGF-β signaling disruption by Doxycycline treatment in K14+ epithelial stem cells. We showed that in mice lacking TGF-β signaling in K14+ cells, invasive carcinomas developed on the ventral surface of the tip of the tongue, while filiform papillae on the dorsal surface showed different pathological changes from the tip to the posterior of the tongue. In addition, acetylation levels of histone H4 and histone H3 rapidly increased, while pMAPK activity was enhanced and Jagged2 inactivated in lingual epithelia after disruption of TGF-β signaling. Our results contribute to the understanding of TGF-β signaling in regulating homeostasis and carcinogenesis in lingual epithelia. Copyright © 2013 Wiley Periodicals, Inc.

Dogs cannot bark: event-related brain responses to true and false negated statements as indicators of higher-order conscious processing.

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Herbert, Cornelia; Kübler, Andrea

2011-01-01

The present study investigated event-related brain potentials elicited by true and false negated statements to evaluate if discrimination of the truth value of negated information relies on conscious processing and requires higher-order cognitive processing in healthy subjects across different levels of stimulus complexity. The stimulus material consisted of true and false negated sentences (sentence level) and prime-target expressions (word level). Stimuli were presented acoustically and no overt behavioral response of the participants was required. Event-related brain potentials to target words preceded by true and false negated expressions were analyzed both within group and at the single subject level. Across the different processing conditions (word pairs and sentences), target words elicited a frontal negativity and a late positivity in the time window from 600-1000 msec post target word onset. Amplitudes of both brain potentials varied as a function of the truth value of the negated expressions. Results were confirmed at the single-subject level. In sum, our results support recent suggestions according to which evaluation of the truth value of a negated expression is a time- and cognitively demanding process that cannot be solved automatically, and thus requires conscious processing. Our paradigm provides insight into higher-order processing related to language comprehension and reasoning in healthy subjects. Future studies are needed to evaluate if our paradigm also proves sensitive for the detection of consciousness in non-responsive patients.

Dogs cannot bark: event-related brain responses to true and false negated statements as indicators of higher-order conscious processing.

Directory of Open Access Journals (Sweden)

Cornelia Herbert

Full Text Available The present study investigated event-related brain potentials elicited by true and false negated statements to evaluate if discrimination of the truth value of negated information relies on conscious processing and requires higher-order cognitive processing in healthy subjects across different levels of stimulus complexity. The stimulus material consisted of true and false negated sentences (sentence level and prime-target expressions (word level. Stimuli were presented acoustically and no overt behavioral response of the participants was required. Event-related brain potentials to target words preceded by true and false negated expressions were analyzed both within group and at the single subject level. Across the different processing conditions (word pairs and sentences, target words elicited a frontal negativity and a late positivity in the time window from 600-1000 msec post target word onset. Amplitudes of both brain potentials varied as a function of the truth value of the negated expressions. Results were confirmed at the single-subject level. In sum, our results support recent suggestions according to which evaluation of the truth value of a negated expression is a time- and cognitively demanding process that cannot be solved automatically, and thus requires conscious processing. Our paradigm provides insight into higher-order processing related to language comprehension and reasoning in healthy subjects. Future studies are needed to evaluate if our paradigm also proves sensitive for the detection of consciousness in non-responsive patients.

Contrastive Analysis and Research on Negative Pressure Beam Tube System and Positive Pressure Beam Tube System for Mine Use

Science.gov (United States)

Wang, Xinyi; Shen, Jialong; Liu, Xinbo

2018-01-01

Against the technical defects of universally applicable beam tube monitoring system at present, such as air suction in the beam tube, line clogging, long sampling time, etc., the paper analyzes the current situation of the spontaneous combustion fire disaster forecast of mine in our country and these defects one by one. On this basis, the paper proposes a research thought that improving the positive pressure beam tube so as to substitute the negative pressure beam tube. Then, the paper introduces the beam tube monitoring system based on positive pressure technology through theoretical analysis and experiment. In the comparison with negative pressure beam tube, the paper concludes the advantage of the new system and draws the conclusion that the positive pressure beam tube is superior to the negative pressure beam tube system both in test result and test time. At last, the paper proposes prospect of the beam tube monitoring system based on positive pressure technology.

Appetitive motivation and negative emotion reactivity among remitted depressed youth.

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Hankin, Benjamin L; Wetter, Emily K; Flory, Kate

2012-01-01

Depression has been characterized as involving altered appetitive motivation and emotional reactivity. Yet no study has examined objective indices of emotional reactivity when the appetitive/approach system is suppressed in response to failure to attain a self-relevant goal and desired reward. Three groups of youth (N = 98, ages 9-15; remitted depressed, n = 34; externalizing disordered without depression, n = 30; and healthy controls, n = 34) participated in a novel reward striving task designed to activate the appetitive/approach motivation system. Objective facial expressions of emotion were videotaped and coded throughout both failure (i.e., nonreward) and control (success and reward) conditions. Observational coding of facial expressions as well as youths' subjective emotion reports showed that the remitted depressed youth specifically exhibited more negative emotional reactivity to failure in the reward striving task, but not the control condition. Neither externalizing disordered (i.e., attention deficit hyperactivity disorder, conduct disorder, and/or oppositional defiant disorder) nor control youth displayed greater negative emotional reactivity in either the failure or control condition. Findings suggest that depression among youth is related to dysregulated appetitive motivation and associated negative emotional reactivity after failing to achieve an important, self-relevant goal and not attaining reward. These deficits in reward processing appear to be specific to depression as externalizing disordered youth did not display negative emotional reactivity to failure after their appetitive motivation system was activated.

Bcl-2 protein expression in mucoepidermoid carcinoma of salivary glands: a single institution experience.

Science.gov (United States)

Janjua, Omer Sefvan; Qureshi, Sana Mehmood; Khan, Tariq Sarfraz; Alamgir, Wajiha

2012-01-01

Mucoepidermoid carcinoma is the most common salivary gland tumor with varying behavior among different histopathological grades. The objective of this study was to determine the expression of Bcl-2 protein in mucoepidermoid carcinoma (MEC) and to correlate with histological grades. The records of 40 cases of MEC were collected from the histopathology department. Fresh slides were prepared and fresh diagnoses were made using the grading criteria for MEC. Immunohistochemical markers for Bcl-2 were applied and the results analyzed using the chi-square test. Of 40 cases, 20 were males and 20 were females. The range in age of the patients was 6 to 67 years mean (SD) was 42.6 (1.85) years. Twenty-two were low grade (55%), 11 high grade (27.5%) and 7 (17.5%) were intermediate grade MEC. Among these 40 cases, Bcl-2 expression was positive in 24 cases and negative in 16 cases. In 22 cases of low-grade MEC, 19 were positive while only 3 were negative. In high-grade tumors, all 11 cases were found to have a negative expression of Bcl-2 protein. In intermediate-grade MEC, 5 cases showed positive expression while only 2 cases showed negative expression. Bcl-2 protein expression showed positive expression in low-grade and negative expression in high-grade MEC. Intermediate grade showed more than 50% positive results for Bcl-2. Correlation between grades of MEC and expression of Bcl-2 is statistically significant and can be used for the depicting the prognosis of MEC along with other prognostic and clinico-pathological parameters.

Large vehicle portal monitor for perimeter safeguards applications

International Nuclear Information System (INIS)

Caldwell, J.T.; Atwater, H.F.; Bernard, W.; Bieri, J.M.; Shunk, E.R.

1979-01-01

We have developed a class of vehicle portal monitors based on shielded 4π geometry neutron counting. we have derived and experimentally verified an analytical expression relating the detection sensitivity of the neutron tunnel vehicle portal monitor to four design parameters of the system. For a given number of neutron detectors, this design achieves one or more orders of magnitude improvement in nuclear materials detection sensitivity over previous vehicle portal monitors

BRCA1-IRIS regulates cyclin D1 expression in breast cancer cells

International Nuclear Information System (INIS)

Nakuci, Enkeleda; Mahner, Sven; DiRenzo, James; ElShamy, Wael M.

2006-01-01

The regulator of cell cycle progression, cyclin D1, is up-regulated in breast cancer cells; its expression is, in part, dependent on ERα signaling. However, many ERα-negative tumors and tumor cell lines (e.g., SKBR3) also show over-expression of cyclin D1. This suggests that, in addition to ERα signaling, cyclin D1 expression is under the control of other signaling pathways; these pathways may even be over-expressed in the ERα-negative cells. We previously noticed that both ERα-positive and -negative cell lines over-express BRCA1-IRIS mRNA and protein. Furthermore, the level of over-expression of BRCA1-IRIS in ERα-negative cell lines even exceeded its over-expression level in ERα-positive cell lines. In this study, we show that: (1) BRCA1-IRIS forms complex with two of the nuclear receptor co-activators, namely, SRC1 and SRC3 (AIB1) in an ERα-independent manner. (2) BRCA1-IRIS alone, or in connection with co-activators, is recruited to the cyclin D1 promoter through its binding to c-Jun/AP1 complex; this binding activates the cyclin D1 expression. (3) Over-expression of BRCA1-IRIS in breast cells over-activates JNK/c-Jun; this leads to the induction of cyclin D1 expression and cellular proliferation. (4) BRCA1-IRIS activation of JNK/c-Jun/AP1 appears to account for this, because in cells that were depleted from BRCA1-IRIS, JNK remained inactive. However, depletion of SRC1 or SRC3 instead reduced c-Jun expression. Our data suggest that this novel signaling pathway links BRCA1-IRIS to cellular proliferation through c-Jun/AP1 nuclear pathway; finally, this culminates in the increased expression of the cyclin D1 gene

Chinese adolescents' reports of covert parental monitoring: Comparisons with overt monitoring and links with information management.

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Hawk, Skyler T

2017-02-01

This study compared Chinese adolescents' reports of covert parental monitoring with the overt strategies of solicitation and control. We investigated these behaviors in terms of unique associations with adolescents' perceived privacy invasion and the information management behaviors of disclosure and secrecy. High school students (N = 455, 61.5% female; M age  = 17.39, SD = 0.83) from a predominantly rural province of Mainland China reported a high incidence of covert monitoring (60.40%). Covert monitoring predicted privacy invasion more strongly than solicitation or control. Solicitation positively predicted disclosure, while covert monitoring negatively predicted disclosure and positively predicted secrecy. Privacy invasion fully mediated links between covert monitoring and information management. These latter effects were significantly stronger for girls than for boys. Similar to Western adolescents, Chinese youth might apply selective resistance when parents violate their personal domain. The findings suggest linkage between some parental monitoring behaviors and disruptions in Chinese family communication. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

MicroPET/CT Imaging of AXL Downregulation by HSP90 Inhibition in Triple-Negative Breast Cancer

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Wanqin Wang

2017-01-01

Full Text Available AXL receptor tyrosine kinase is overexpressed in a number of solid tumor types including triple-negative breast cancer (TNBC. AXL is considered an important regulator of epithelial-to-mesenchymal transition (EMT and a potential therapeutic target for TNBC. In this work, we used microPET/CT with 64Cu-labeled anti-human AXL antibody (64Cu-anti-hAXL to noninvasively interrogate the degradation of AXL in vivo in response to 17-allylamino-17-demethoxygeldanamycin (17-AAG, a potent inhibitor of HSP90. 17-AAG treatment caused significant decline in AXL expression in orthotopic TNBC MDA-MB-231 tumors, inhibited EMT, and delayed tumor growth in vivo, resulting in significant reduction in tumor uptake of 64Cu-anti-hAXL as clearly visualized by microPET/CT. Our data indicate that 64Cu-anti-hAXL can be useful for monitoring anti-AXL therapies and for assessing inhibition of HSP90 molecular chaperone using AXL as a molecular surrogate.

Facial Expressivity at 4 Months: A Context by Expression Analysis.

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Bennett, David S; Bendersky, Margaret; Lewis, Michael

2002-01-01

The specificity predicted by differential emotions theory (DET) for early facial expressions in response to 5 different eliciting situations was studied in a sample of 4-month-old infants (n = 150). Infants were videotaped during tickle, sour taste, jack-in-the-box, arm restraint, and masked-stranger situations and their expressions were coded second by second. Infants showed a variety of facial expressions in each situation; however, more infants exhibited positive (joy and surprise) than negative expressions (anger, disgust, fear, and sadness) across all situations except sour taste. Consistent with DET-predicted specificity, joy expressions were the most common in response to tickling, and were less common in response to other situations. Surprise expressions were the most common in response to the jack-in-the-box, as predicted, but also were the most common in response to the arm restraint and masked-stranger situations, indicating a lack of specificity. No evidence of predicted specificity was found for anger, disgust, fear, and sadness expressions. Evidence of individual differences in expressivity within situations, as well as stability in the pattern across situations, underscores the need to examine both child and contextual factors in studying emotional development. The results provide little support for the DET postulate of situational specificity and suggest that a synthesis of differential emotions and dynamic systems theories of emotional expression should be considered.

The Negative Sign and Exponential Expressions: Unveiling Students' Persistent Errors and Misconceptions

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Cangelosi, Richard; Madrid, Silvia; Cooper, Sandra; Olson, Jo; Hartter, Beverly

2013-01-01

The purpose of this study was to determine whether or not certain errors made when simplifying exponential expressions persist as students progress through their mathematical studies. College students enrolled in college algebra, pre-calculus, and first- and second-semester calculus mathematics courses were asked to simplify exponential…

Recruitment of HDAC4 by transcription factor YY1 represses HOXB13 to affect cell growth in AR-negative prostate cancers

DEFF Research Database (Denmark)

Ren, Guoling; Zhang, Guocui; Dong, Zhixiong

2008-01-01

HOXB13 is a homeodomain protein implicated to play a role in growth arrest in AR (androgen receptor)-negative prostate cancer cells. Expression of HOXB13 is restricted to the AR-expressing prostate cells. In this report, we demonstrate that the HDAC inhibitor NaB (sodium butyrate) was able...... to induce cell growth arrest and to increase HOXB13 expression in AR-negative prostate cancer cells. We also show that both HDAC4 and YY1 participated in the repression of HOXB13 expression through an epigenetic mechanism involving histone acetylation modification. Specifically, co...

Cyclin D1 expression in prostate carcinoma

Energy Technology Data Exchange (ETDEWEB)

Pereira, R.A.; Ravinal, R.C.; Costa, R.S.; Lima, M.S. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Patologia, Ribeirão Preto, SP, Brasil, Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Tucci, S. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Cirurgia e Anatomia, Divisão de Urologia, Ribeirão Preto, SP, Brasil, Divisão de Urologia, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Muglia, V.F. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Medicina Interna (Centro de Ciência da Imagem), Ribeirão Preto, SP, Brasil, Departamento de Medicina Interna (Centro de Ciência da Imagem), Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Reis, R.B. Dos [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Cirurgia e Anatomia, Divisão de Urologia, Ribeirão Preto, SP, Brasil, Divisão de Urologia, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Silva, G.E.B. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Patologia, Ribeirão Preto, SP, Brasil, Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

2014-05-09

The purpose of this study was to investigate the relationship between cyclin D1 expression and clinicopathological parameters in patients with prostate carcinoma. We assessed cyclin D1 expression by conventional immunohistochemistry in 85 patients who underwent radical prostatectomy for prostate carcinoma and 10 normal prostate tissue samples retrieved from autopsies. We measured nuclear immunostaining in the entire tumor area and based the results on the percentage of positive tumor cells. The preoperative prostate-specific antigen (PSA) level was 8.68±5.16 ng/mL (mean±SD). Cyclin D1 staining was positive (cyclin D1 expression in >5% of tumor cells) in 64 cases (75.4%) and negative (cyclin D1 expression in ≤5% of tumor cells) in 21 cases (including 15 cases with no immunostaining). Normal prostate tissues were negative for cyclin D1. Among patients with a high-grade Gleason score (≥7), 86% of patients demonstrated cyclin D1 immunostaining of >5% (P<0.05). In the crude analysis of cyclin D1 expression, the high-grade Gleason score group showed a mean expression of 39.6%, compared to 26.9% in the low-grade Gleason score group (P<0.05). Perineural invasion tended to be associated with cyclin D1 expression (P=0.07), whereas cyclin D1 expression was not associated with PSA levels or other parameters. Our results suggest that high cyclin D1 expression could be a potential marker for tumor aggressiveness.

Cyclin D1 expression in prostate carcinoma

International Nuclear Information System (INIS)

Pereira, R.A.; Ravinal, R.C.; Costa, R.S.; Lima, M.S.; Tucci, S.; Muglia, V.F.; Reis, R.B. Dos; Silva, G.E.B.

2014-01-01

The purpose of this study was to investigate the relationship between cyclin D1 expression and clinicopathological parameters in patients with prostate carcinoma. We assessed cyclin D1 expression by conventional immunohistochemistry in 85 patients who underwent radical prostatectomy for prostate carcinoma and 10 normal prostate tissue samples retrieved from autopsies. We measured nuclear immunostaining in the entire tumor area and based the results on the percentage of positive tumor cells. The preoperative prostate-specific antigen (PSA) level was 8.68±5.16 ng/mL (mean±SD). Cyclin D1 staining was positive (cyclin D1 expression in >5% of tumor cells) in 64 cases (75.4%) and negative (cyclin D1 expression in ≤5% of tumor cells) in 21 cases (including 15 cases with no immunostaining). Normal prostate tissues were negative for cyclin D1. Among patients with a high-grade Gleason score (≥7), 86% of patients demonstrated cyclin D1 immunostaining of >5% (P<0.05). In the crude analysis of cyclin D1 expression, the high-grade Gleason score group showed a mean expression of 39.6%, compared to 26.9% in the low-grade Gleason score group (P<0.05). Perineural invasion tended to be associated with cyclin D1 expression (P=0.07), whereas cyclin D1 expression was not associated with PSA levels or other parameters. Our results suggest that high cyclin D1 expression could be a potential marker for tumor aggressiveness

Expressing and Amplifying Positive Emotions Facilitate Goal Attainment in Workplace Interactions

Science.gov (United States)

Wong, Elena; Tschan, Franziska; Messerli, Laurence; Semmer, Norbert K.

2013-01-01

Expressing emotions has social functions; it provides information, affects social interactions, and shapes relationships with others. Expressing positive emotions could be a strategic tool for improving goal attainment during social interactions at work. Such effects have been found in research on social contagion, impression management, and emotion work. However, expressing emotions one does not feel entails the risk of being perceived as inauthentic. This risk may well be worth taking when the emotions felt are negative, as expressing negative emotions usually has negative effects. When experiencing positive emotions, however, expressing them authentically promises benefits, and the advantage of amplifying them is not so obvious. We postulated that expressing, and amplifying, positive emotions would foster goal attainment in social interactions at work, particularly when dealing with superiors. Analyses are based on 494 interactions involving the pursuit of a goal by 113 employes. Multilevel analyses, including polynomial analyses, show that authentic display of positive emotions supported goal attainment throughout. However, amplifying felt positive emotions promoted goal attainment only in interactions with superiors, but not with colleagues. Results are discussed with regard to the importance of hierarchy for detecting, and interpreting, signs of strategic display of positive emotions. PMID:23675358

Expressing and amplifying positive emotions facilitate goal attainment in workplace interactions

Directory of Open Access Journals (Sweden)

Elena eWong

2013-05-01

Full Text Available Expressing emotions has social functions; it provides information, affects social interactions, and shapes relationships with others. Expressing positive emotions could be a strategic tool for improving goal attainment during social interactions at work. Such effects have been found in research on social contagion, impression management, and emotion work. However, expressing emotions one does not feel entails the risk of being perceived as inauthentic. This risk may well be worth taking when the emotions felt are negative, as expressing negative emotions usually has negative effects. When experiencing positive emotions, however, expressing them authentically promises benefits, and the advantage of amplifying them is not so obvious. We postulated that expressing, and amplifying, positive emotions would foster goal attainment in social interactions at work, particularly when dealing with superiors. Analyses are based on 494 interactions involving the pursuit of a goal by 113 employees. Multilevel analyses, including polynomial analyses, show that authentic display of positive emotions supported goal attainment throughout. However, amplifying felt positive emotions promoted goal attainment only in interactions with superiors, but not with colleagues. Results are discussed with regard to the importance of hierarchy for detecting, and interpreting, signs of strategic display of positive emotions.

Increased gene expression of histone deacetylases in patients with Philadelphia-negative chronic myeloproliferative neoplasms

DEFF Research Database (Denmark)

Skov, Vibe; Larsen, Thomas Stauffer; Thomassen, Mads

2012-01-01

Abstract Myeloproliferation, myeloaccumulation (decreased apoptosis), inflammation, bone marrow fibrosis and angiogenesis are cardinal features of the Philadelphia-negative chronic myeloproliferative neoplasms: essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF...

Expression of RECK and matrix metalloproteinase-2 in ameloblastoma

International Nuclear Information System (INIS)

Zhang, Bin; Zhang, Jin; Xu, Zhi-Ying; Xie, Hong-Liang

2009-01-01

Ameloblastoma is a frequent odontogenic benign tumor characterized by local invasiveness, high risk of recurrence and occasional metastasis and malignant transformation. Matrix metalloproteinase-2 (MMP-2) promotes tumor invasion and progression by destroying the extracellular matrix (ECM) and basement membrane. For this proteolytic activity, the endogenous inhibitor is reversion-inducing cysteine rich protein with Kazal motifs (RECK). The aim of this study was to characterize the relationship between RECK and MMP-2 expression and the clinical manifestation of ameloblastoma. Immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) were employed to detect the protein and mRNA expression of RECK and MMP-2 in keratocystic odontogenic tumor (KCOT), ameloblastoma and ameloblastic carcinoma. RECK protein expression was significantly reduced in KCOT (87.5%), ameloblastoma (56.5%) and ameloblastic carcinoma (0%) (P < 0.01), and was significantly lower in recurrent ameloblastoma compared with primary ameloblastoma (P < 0.01), but did not differ by histological type of ameloblastoma. MMP-2 protein expression was significantly higher in ameloblastoma and ameloblastic carcinoma compared with KCOT (P < 0.01). RECK mRNA expression was significantly lower in ameloblastoma than in KCOT (P < 0.01), lower in recurrent ameloblastoma than in primary ameloblastoma, and was negative in ameloblastic carcinoma. MMP-2 mRNA expression was significantly higher in ameloblastoma compared with KCOT (P < 0.01), but was no different in recurrent ameloblastoma versus primary ameloblastoma. RECK protein expression was negatively associated with MMP-2 protein expression in ameloblastoma (r = -0.431, P < 0.01). Low or no RECK expression and increased MMP-2 expression may be associated with negative clinical findings in ameloblastoma. RECK may participate in the invasion, recurrence and malignant transformation of ameloblastoma by regulating MMP-2 at the post

Impairment of vocal expression of negative emotions in patients with Alzheimer`s disease

Directory of Open Access Journals (Sweden)

Kyung-Hun eHan

2014-05-01

Full Text Available The vocal expression of emotions (EE in the retrieval of events from autobiographical memory was investigated in patients in early stages of Alzheimer’s disease (AD. 21 AD patients and 19 controls were interviewed, and EE of the reported memories was rated by 8 independent evaluators. The AD group had lower EE of both recent and remote memory than controls, although EE in remote memories was better preserved in both groups. We observed positive correlations between EE and indicators of cognitive competence in AD patients. AD Patients are impaired in their ability to express emotions at early stages of the disease, and EE seems to deteriorate along with the progression of cognitive impairment.

Assays for noninvasive imaging of reporter gene expression

International Nuclear Information System (INIS)

Gambhir, S.S.; Barrio, J.R.; Herschman, H.R.; Phelps, M.E.

1999-01-01

Repeated, noninvasive imaging of reporter gene expression is emerging as a valuable tool for monitoring the expression of genes in animals and humans. Monitoring of organ/cell transplantation in living animals and humans, and the assessment of environmental, behavioral, and pharmacologic modulation of gene expression in transgenic animals should soon be possible. The earliest clinical application is likely to be monitoring human gene therapy in tumors transduced with the herpes simplex virus type 1 thymidine kinase (HSV1-tk) suicide gene. Several candidate assays for imaging reporter gene expression have been studied, utilizing cytosine deaminase (CD), HSV1-tk, and dopamine 2 receptor (D2R) as reporter genes. For the HSV1-tk reporter gene, both uracil nucleoside derivatives (e.g., 5-iodo-2'-fluoro-2'-deoxy-1-β-D-arabinofuranosyl-5-iodouracil [FIAU] labeled with 124 I, 131 I ) and acycloguanosine derivatives {e.g., 8-[ 18 F]fluoro-9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]guanine (8-[ 18 F]-fluoroganciclovir) ([ 18 F]FGCV), 9-[(3-[ 18 F]fluoro-1-hydroxy-2-propoxy)methyl]guanine ([ 18 F]FHPG)} have been investigated as reporter probes. For the D2R reporter gene, a derivative of spiperone {3-(2'-[ 18 F]-Fluoroethyl)spiperone ([ 18 F]FESP)} has been used with positron emission tomography (PET) imaging. In this review, the principles and specific assays for imaging reporter gene expression are presented and discussed. Specific examples utilizing adenoviral-mediated delivery of a reporter gene as well as tumors expressing reporter genes are discussed

Evaluating guilt and shame in an expressive writing alcohol intervention.

Science.gov (United States)

Rodriguez, Lindsey M; Young, Chelsie M; Neighbors, Clayton; Campbell, Michelle T; Lu, Qian

2015-08-01

Expressive writing interventions have shown positive physical and psychological health benefits over time, with the presumed mechanism being emotional disclosure. However, work utilizing expressive writing in behavior change has been minimal. The current research applied the expressive writing paradigm to reduce drinking intentions among college students, and evaluated the role of event-related guilt and shame in intervention effects. College students (N=429) completed a baseline survey and were randomly assigned to one of three conditions: Negative (write about a heavy drinking event that was negative); Positive (write about a heavy drinking event that was positive); or Neutral (write about their first day of college). After writing, readiness to change and future drinking intentions were assessed. Results revealed intervention effects on intended drinks per week and intended number of drinks during peak and typical drinking occasions. Participants in the negative condition also displayed higher levels of event-related guilt and shame. Results showed that guilt mediated intervention effects on readiness to change, which also mediated the association between guilt-reparative behavior and drinking intentions. Results provide initial support for an expressive writing intervention on alcohol use and underscore the importance of eliciting emotions associated with reparative behavior when considering negative past experiences and future behavior change. Copyright © 2015 Elsevier Inc. All rights reserved.

Basic principles of test-negative design in evaluating influenza vaccine effectiveness.

Science.gov (United States)

Fukushima, Wakaba; Hirota, Yoshio

2017-08-24

Based on the unique characteristics of influenza, the concept of "monitoring" influenza vaccine effectiveness (VE) across the seasons using the same observational study design has been developed. In recent years, there has been a growing number of influenza VE reports using the test-negative design, which can minimize both misclassification of diseases and confounding by health care-seeking behavior. Although the test-negative designs offer considerable advantages, there are some concerns that widespread use of the test-negative design without knowledge of the basic principles of epidemiology could produce invalid findings. In this article, we briefly review the basic concepts of the test-negative design with respect to classic study design such as cohort studies or case-control studies. We also mention selection bias, which may be of concern in some countries where rapid diagnostic testing is frequently used in routine clinical practices, as in Japan. Copyright © 2017. Published by Elsevier Ltd.

Negative regulation of neuronal cell differentiation by INHAT subunit SET/TAF-Iβ.

Science.gov (United States)

Kim, Dong-Wook; Kim, Kee-Beom; Kim, Ji-Young; Lee, Kyu-Sun; Seo, Sang-Beom

2010-09-24

Epigenetic modification plays an important role in transcriptional regulation. As a subunit of the INHAT (inhibitor of histone acetyltransferases) complex, SET/TAF-Iβ evidences transcriptional repression activity. In this study, we demonstrate that SET/TAF-Iβ is abundantly expressed in neuronal tissues of Drosophila embryos. It is expressed at high levels prior to and in early stages of neuronal development, and gradually reduced as differentiation proceeds. SET/TAF-Iβ binds to the promoters of a subset of neuronal development markers and negatively regulates the transcription of these genes. The results of this study show that the knockdown of SET/TAF-Iβ by si-RNA induces neuronal cell differentiation, thus implicating SET/TAF-Iβ as a negative regulator of neuronal development. Copyright © 2010 Elsevier Inc. All rights reserved.

Impact of Sleep Quality on Amygdala Reactivity, Negative Affect, and Perceived Stress

Science.gov (United States)

Prather, Aric A.; Bogdan, Ryan; Ahmad R. Hariri, PhD

2013-01-01

Objective Research demonstrates a negative impact of sleep disturbance on mood and affect; however, the biological mechanisms mediating these links are poorly understood. Amygdala reactivity to negative stimuli has emerged as one potential pathway. Here, we investigate the influence of self-reported sleep quality on associations between threat-related amygdala reactivity and measures of negative affect and perceived stress. Methods Analyses on data from 299 participants (125 men, 50.5% white, mean [standard deviation] age = 19.6 [1.3] years) who completed the Duke Neurogenetics Study were conducted. Participants completed several self-report measures of negative affect and perceived stress. Threat-related (i.e., angry and fearful facial expressions) amygdala reactivity was assayed using blood oxygen level–dependent functional magnetic resonance imaging. Global sleep quality was assessed using the Pittsburgh Sleep Quality Index. Results Amygdala reactivity to fearful facial expressions predicted greater depressive symptoms and higher perceived stress in poor (β values = 0.18–1.86, p values .05). In sex-specific analyses, men reporting poorer global sleep quality showed a significant association between amygdala reactivity and levels of depression and perceived stress (β values = 0.29–0.44, p values < .05). In contrast, no significant associations were observed in men reporting good global sleep quality or in women, irrespective of sleep quality. Conclusions This study provides novel evidence that self-reported sleep quality moderates the relationships between amygdala reactivity, negative affect, and perceived stress, particularly among men. PMID:23592753

Processing of unattended facial emotions: a visual mismatch negativity study.

Science.gov (United States)

Stefanics, Gábor; Csukly, Gábor; Komlósi, Sarolta; Czobor, Pál; Czigler, István

2012-02-01

Facial emotions express our internal states and are fundamental in social interactions. Here we explore whether the repetition of unattended facial emotions builds up a predictive representation of frequently encountered emotions in the visual system. Participants (n=24) were presented peripherally with facial stimuli expressing emotions while they performed a visual detection task presented in the center of the visual field. Facial stimuli consisted of four faces of different identity, but expressed the same emotion (happy or fearful). Facial stimuli were presented in blocks of oddball sequence (standard emotion: p=0.9, deviant emotion: p=0.1). Event-related potentials (ERPs) to the same emotions were compared when the emotions were deviant and standard, respectively. We found visual mismatch negativity (vMMN) responses to unattended deviant emotions in the 170-360 ms post-stimulus range over bilateral occipito-temporal sites. Our results demonstrate that information about the emotional content of unattended faces presented at the periphery of the visual field is rapidly processed and stored in a predictive memory representation by the visual system. We also found evidence that differential processing of deviant fearful faces starts already at 70-120 ms after stimulus onset. This finding shows a 'negativity bias' under unattended conditions. Differential processing of fearful deviants were more pronounced in the right hemisphere in the 195-275 ms and 360-390 ms intervals, whereas processing of happy deviants evoked larger differential response in the left hemisphere in the 360-390 ms range, indicating differential hemispheric specialization for automatic processing of positive and negative affect. Copyright © 2011 Elsevier Inc. All rights reserved.

Design for relaxation during milk expression using biofeedback

NARCIS (Netherlands)

Feijs, L.M.G.; Kierkels, J.G.T.; Marcus, A.

2013-01-01

Many women experience difficulty expressing milk using a breast pump. A negative influence upon their success is stress, hampering the milk ejection reflex. We explore biofeedback to enhance relaxation during milk expression. We discuss context, the principles of biofeedback and the design of an

Expressive Dissonance: When Emotional Inconsistency Arouses Dissonance

Directory of Open Access Journals (Sweden)

Audrey Pelt

2018-05-01

Full Text Available The aim of the two studies was to explore a new dissonance paradigm–expressive dissonance–based on the inconsistency between what people feel and what people express behaviorally. Expressive dissonance was aroused by asking participants to watch a film with a high emotional content, either positive (joy or negative (sadness. In the no-dissonance condition, they received the instruction to naturally watch the film. In the expressive dissonance condition, they received the instruction to facially express emotions that were the opposite of what they felt. We expected that the expressive dissonance situation would: 1 require cognitive resources leading to a decrease in cognitive performance (studies 1 and 2; 2 be accompanied by emotional regulation strategies (study 1; 3 be accompanied by an increase in dissonance-related affects (study 2. Although our results (studies 1 and 2 corroborated those obtained previously in terms of performance, they also showed that participants in the expressive dissonance situation use emotional regulation strategies: exaggeration and suppression (study 1, and that they felt self-directed negative affects (study 2, just like the participants in a cognitive dissonance situation. These first results allowed us to establish a theoretical bridge between the theories of emotions–particularly those related to the emotional regulation processes–and to widen the scope of relevance of the dissonance theory.

Performance monitoring and error significance in patients with obsessive-compulsive disorder.

Science.gov (United States)

Endrass, Tanja; Schuermann, Beate; Kaufmann, Christan; Spielberg, Rüdiger; Kniesche, Rainer; Kathmann, Norbert

2010-05-01

Performance monitoring has been consistently found to be overactive in obsessive-compulsive disorder (OCD). The present study examines whether performance monitoring in OCD is adjusted with error significance. Therefore, errors in a flanker task were followed by neutral (standard condition) or punishment feedbacks (punishment condition). In the standard condition patients had significantly larger error-related negativity (ERN) and correct-related negativity (CRN) ampliudes than controls. But, in the punishment condition groups did not differ in ERN and CRN amplitudes. While healthy controls showed an amplitude enhancement between standard and punishment condition, OCD patients showed no variation. In contrast, group differences were not found for the error positivity (Pe): both groups had larger Pe amplitudes in the punishment condition. Results confirm earlier findings of overactive error monitoring in OCD. The absence of a variation with error significance might indicate that OCD patients are unable to down-regulate their monitoring activity according to external requirements. Copyright 2010 Elsevier B.V. All rights reserved.

A large-scale analysis of sex differences in facial expressions.

Directory of Open Access Journals (Sweden)

Daniel McDuff

Full Text Available There exists a stereotype that women are more expressive than men; however, research has almost exclusively focused on a single facial behavior, smiling. A large-scale study examines whether women are consistently more expressive than men or whether the effects are dependent on the emotion expressed. Studies of gender differences in expressivity have been somewhat restricted to data collected in lab settings or which required labor-intensive manual coding. In the present study, we analyze gender differences in facial behaviors as over 2,000 viewers watch a set of video advertisements in their home environments. The facial responses were recorded using participants' own webcams. Using a new automated facial coding technology we coded facial activity. We find that women are not universally more expressive across all facial actions. Nor are they more expressive in all positive valence actions and less expressive in all negative valence actions. It appears that generally women express actions more frequently than men, and in particular express more positive valence actions. However, expressiveness is not greater in women for all negative valence actions and is dependent on the discrete emotional state.

"Straight-acting gays": the relationship between masculine consciousness, anti-effeminacy, and negative gay identity.

Science.gov (United States)

Sánchez, Francisco J; Vilain, Eric

2012-02-01

Some gay men are preoccupied with traditional notions of masculinity and express negative feelings towards effeminate behavior in gay men. Various scholars have speculated that such attitudes by gay men reflect internalized negative feelings about being gay. Thus, we sought to assess the importance of masculinity among gay men, to compare their ideal versus perceived masculinity-femininity, to ask how gay men assess masculinity, and to test whether masculine consciousness and anti-effeminacy could predict negative feelings about being gay. Results from an online survey of 751 gay men in the United States (MAge=32.64 years, SD=11.94) showed that the majority rated masculinity for themselves and in a same-sex partner as important, and they ideally wished that their behavior was more masculine (Cohen's d=.42) and less feminine (d=.42) than they perceived it to be. Furthermore, one's behavior was more important than how one looks when assessing masculinity. A multiple regression analysis showed that the degree to which they were preoccupied with masculinity and expressed anti-effeminacy accounted for 30% of the variance in negative feelings about being gay. These finding further support the idea that masculinity is an important construct for gay men and that masculine consciousness and anti-effeminacy are related to negative feelings about being gay.

Active and Passive Optical Imaging Modality for Unobtrusive Cardiorespiratory Monitoring and Facial Expression Assessment.

Science.gov (United States)

Blazek, Vladimir; Blanik, Nikolai; Blazek, Claudia R; Paul, Michael; Pereira, Carina; Koeny, Marcus; Venema, Boudewijn; Leonhardt, Steffen

2017-01-01

Because of their obvious advantages, active and passive optoelectronic sensor concepts are being investigated by biomedical research groups worldwide, particularly their camera-based variants. Such methods work noninvasively and contactless, and they provide spatially resolved parameter detection. We present 2 techniques: the active photoplethysmography imaging (PPGI) method for detecting dermal blood perfusion dynamics and the passive infrared thermography imaging (IRTI) method for detecting skin temperature distribution. PPGI is an enhancement of classical pulse oximetry. Approved algorithms from pulse oximetry for the detection of heart rate, heart rate variability, blood pressure-dependent pulse wave velocity, pulse waveform-related stress/pain indicators, respiration rate, respiratory variability, and vasomotional activity can easily be adapted to PPGI. Although the IRTI method primarily records temperature distribution of the observed object, information on respiration rate and respiratory variability can also be derived by analyzing temperature change over time, for example, in the nasal region, or through respiratory movement. Combined with current research areas and novel biomedical engineering applications (eg, telemedicine, tele-emergency, and telemedical diagnostics), PPGI and IRTI may offer new data for diagnostic purposes, including assessment of peripheral arterial and venous oxygen saturation (as well as their differences). Moreover, facial expressions and stress and/or pain-related variables can be derived, for example, during anesthesia, in the recovery room/intensive care unit and during daily activities. The main advantages of both monitoring methods are unobtrusive data acquisition and the possibility to assess vital variables for different body regions. These methods supplement each other to enable long-term monitoring of physiological effects and of effects with special local characteristics. They also offer diagnostic advantages for

Interpreting infant emotional expressions: Parenthood has differential effects on men and women.

Science.gov (United States)

Parsons, Christine E; Young, Katherine S; Jegindoe Elmholdt, Else-Marie; Stein, Alan; Kringelbach, Morten L

2017-03-01

Interpreting and responding to an infant's emotional cues is a fundamental parenting skill. Responsivity to infant cues is frequently disrupted in depression, impacting negatively on child outcomes, which underscores its importance. It is widely assumed that women, and in particular mothers, show greater attunement to infants than do men. However, empirical evidence for sex and parental status effects, particularly in relation to perception of infant emotion, has been lacking. In this study, men and women with and without young infants were asked to rate valence in a range of infant facial expressions, on a scale of very positive to very negative. Results suggested complex interaction effects between parental status, sex, and the facial expression being rated. Mothers provided more positive ratings of the happy expressions and more extreme ratings of the intense emotion expressions than fathers, but non-mothers and non-fathers did not. Low-level depressive symptoms were also found to correlate with more negative ratings of negative infant facial expressions across the entire sample. Overall, these results suggest that parental status might have differential effects on men and women's appraisal of infant cues. Differences between fathers' and mothers' perceptions of infant emotion might be of interest in understanding variance in interaction styles, such as proportion of time spent in play.

Effluent and environmental monitoring of Chalk River Laboratories

Energy Technology Data Exchange (ETDEWEB)

Pilgrim, T.; De Waele, C.; Gallagher, C. [Atomic Energy of Canada Limited, Chalk River, ON (Canada)

2014-07-01

Atomic Energy of Canada Limited's (AECL's) Environmental Protection Program has been gathering environmental monitoring data at its Chalk River Laboratories (CRL) for over 60 years. The comprehensive effluent and environmental monitoring program at CRL consists of more than 600 sampling locations, including the Ottawa River, with approximately 60,000 analyses performed on air and liquid effluent parameters each year. Monitoring for a variety of radiological and non-radiological parameters is regularly conducted on various media, including ambient air, foodstuff (e.g. milk, fish, garden produce, large game, and farm animals), groundwater, Ottawa River water and other surface water on and off-site. The purpose of the monitoring program is to verify that past and current radiological and non-radiological emissions derived from AECL operations and activities, such as process water effluent into the Ottawa River, are below regulatory limits and demonstrate that CRL operations do not negatively affect the quality of water on or leaving the site. In fact, ongoing program reports demonstrate that radiological emissions are well below regulatory limits and have been declining for the past five years, and that non-radiological contaminants do not negatively affect the quality of water on and off the site. Two updated Canadian Standards Association (CSA) standards for Effluent and Environmental monitoring have come into effect and have resulted in some changes to the AECL Program. This presentation will discuss effluent and surface water monitoring results, the observed trends, the changes triggered by the CSA standards, and a path forward for the future. (author)

Expression of CD133 in acute leukemia.

Science.gov (United States)

Tolba, Fetnat M; Foda, Mona E; Kamal, Howyda M; Elshabrawy, Deena A

2013-06-01

There have been conflicting results regarding a correlation between CD133 expression and disease outcome. To assess CD133 expression in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) and to evaluate its correlation with the different clinical and laboratory data as well as its relation to disease outcome, the present study included 60 newly diagnosed acute leukemic patients; 30 ALL patients with a male to female ratio of 1.5:1 and their ages ranged from 9 months to 48 years, and 30 AML patients with a male to female ratio of 1:1 and their ages ranged from 17 to 66 years. Flow cytometric assessment of CD133 expression was performed on blast cells. In ALL, no correlations were elicited between CD133 expression and some monoclonal antibodies, but in AML group, there was a significant positive correlation between CD133 and HLA-DR, CD3, CD7 and TDT, CD13 and CD34. In ALL group, patients with negative CD133 expression achieved complete remission more than patients with positive CD133 expression. In AML group, there was no statistically significant association found between positive CD133 expression and treatment outcome. The Kaplan-Meier curve illustrated a high significant negative correlation between CD133 expression and the overall survival of the AML patients. CD133 expression is an independent prognostic factor in acute leukemia, especially ALL patients and its expression could characterize a group of acute leukemic patients with higher resistance to standard chemotherapy and relapse. CD133 expression was highly associated with poor prognosis in acute leukemic patients.

A Negative Life Event Impairs Psychosocial Stress, Recovery and Running Economy of Runners

NARCIS (Netherlands)

Otter, R. T. A.; Brink, M. S.; Diercks, R. L.; Lemmink, K. A. P. M.

The purpose was to investigate how a negative life event (NLE) affects perceived psychosocial stress, recovery and running economy (RE). Competitive runners were monitored in a prospective non-experimental cohort study over one full training season in which they experienced the same unplanned severe

Electronics system for the 150 kV negative ion test stand at BNL

International Nuclear Information System (INIS)

Larson, R.A.

1977-01-01

The 150 kV test stand at BNL is being used to investigate the extraction, acceleration and transport problems associated with the development of intense negative ion beams. The power supplies associated with these functions as well as the control and monitoring electronics are described

Parents' emotion expression as a predictor of child's social competence: children with or without intellectual disability.

Science.gov (United States)

Green, S; Baker, B

2011-03-01

Parents' expression of positive emotion towards children who are typically developing (TD) is generally associated with better social development. However, the association between parents' negative emotion expression and social development can be positive or negative depending upon a number of factors, including the child's emotion regulation abilities. Given the lower emotion regulation capabilities of children with intellectual disability (ID), we hypothesised that parents' negative emotion expression would be associated with lower social development in children with ID compared to those with TD. Participants were 180 families of children with or without ID enrolled in a longitudinal study. Parents' positive and negative affect were coded live from naturalistic home interactions at child ages 5-8 years, and child's social skills were measured by using mother report at child ages 6-9 years. We examined mothers' and fathers' emotion expression as a time-varying predictor of social skills across ages 5-9 years. Mothers, but not fathers, expressed less positive affect and more negative affect with ID group children. Parents' positive affect expression was related to social skills only for TD children, with mothers' positive affect predicting higher social skills. Contrary to expectations, fathers' positive affect predicted lower social skills. Parents' negative affect predicted significantly lower social skills for children with ID than for children with TD. Findings support the theory that low to moderate levels of negative expression may be less beneficial or detrimental for children with ID compared to children with TD. Implications for further research and intervention are discussed. © 2011 The Authors. Journal of Intellectual Disability Research © 2011 Blackwell Publishing Ltd.

Expression Profiling of Tyrosine Kinase Genes

National Research Council Canada - National Science Library

Weier, Heinz

2000-01-01

... of these genes parallels the progression of tumors to a more malignant phenotype. We developed a DNA micro-array based screening system to monitor the level of expression of tyrosine kinase (tk...

Individual Differences in Working Memory Capacity Predict Action Monitoring and the Error-Related Negativity

Science.gov (United States)

Miller, A. Eve; Watson, Jason M.; Strayer, David L.

2012-01-01

Neuroscience suggests that the anterior cingulate cortex (ACC) is responsible for conflict monitoring and the detection of errors in cognitive tasks, thereby contributing to the implementation of attentional control. Though individual differences in frontally mediated goal maintenance have clearly been shown to influence outward behavior in…

Environmental effects monitoring for exploration drilling

International Nuclear Information System (INIS)

Buchanan, R.A.; Cook, J.A.; Mathieu, A.

2003-01-01

Strategies for monitoring the environmental effects of single exploratory offshore wells on the east coast of Canada were evaluated. The report was compiled from consultations with scientists, regulators and stakeholders as well as a review of regulatory regimes and toxicity results. The aim of the report was to develop a decision tree for determining when to conduct environmental effects monitoring (EEM). Respondents evinced lower levels of concern for single exploratory wells than for production developments. A number of scientists argued for full statistical treatment of all data, and many people argued that more assurance was needed that the marine environment was not being unduly harmed. Respondents also considered that biological effects should be a primary focus, rather than the occurrence of trace chemical signals, and that seabirds and mammals should be monitored. Concern was expressed over the value of data collected from monitoring the effects of exploratory drilling activities. It was suggested that local and site-specific issues should be considered in the design of EEM programs. Respondents expressed strong concern about potential cumulative effects with other industrial activities, and suggested that test cases should be established and monitored to develop a scientific rationale for the inclusion or exclusion of specific variables in future EEM programs. A decision tree was developed based on 3 scenarios: (1) compliance monitoring only in well known areas with no sensitive issues; opportunistic EEM surveys of sediments, benthos, seabirds and marine mammals in shallow or deep areas with no known sensitive issues; and (3) custom EEM surveys for sensitive areas. Currently, there are EEM requirements for drilling exploratory wells offshore Canada's east coast. 58 refs., 2 tabs., 7 figs