bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial Evaluations of a Coastline and Its Close Environment: The Settlement of Dalyan, Muğla, Turkey
Authors: Malkoc Emine , Turel Hatice Sonmez , Kilicaslan Cigdem
Published: September 2011

Dalyan, a Mediterranean coastal settlement in southwestern Turkey, is attracting a great deal of attention due to its natural and cultural value and tourism potential. The aim of this study was to evaluate the Dalyan coastline and its environment as a public open space to find out whether the space meets the needs of users. Responses to a questionnaire were used to propose solutions for developing the area’s performance and identity.

First, the area was divided into six sub-spaces that were evaluated in terms of activities and uses, comfort and image, access and linkage, sociability and sensorial aspects and meeting the users’ expectations. Second, a face-to-face interview was conducted with 255 users. A visual analysis was also conducted. As a result of this research, various sectors of the society were brought together. This research illustrated that the coastline is the most popular sector of Dalyan, and if the suggested development takes place, it would provide an important social environment as well as an open space for community use due to the enhancement of the area’s visual quality and liveability.
Maintaining friendships in early stage dementia: Factors to consider
Authors: Harris Phyllis Braudy
Published: September 2011

Friendships and the importance of social connectiveness play a critical role in aging well, regardless of gender, race, social class, or impairment. Yet, dementia takes its toll on social relationships, and many friends withdraw and ‘disappear’, because they can no longer bear to see the changes that are taking place in their diagnosed friend. The dementia care literature documents this abandonment; however, this study examines the opposite occurrence. In order to understand more clearly the role of long-term friendships and how such friendships remain and continue, despite the diagnosis of dementia, this qualitative study examines in depth eight people in the early stages of dementia who have been able to maintain strong friendships despite the diagnosis. Factors that seem to play important roles are: (1) the importance of the friendships, (2) factors affecting the quality of the relationships, (3) mutually beneficial relationships, (4) core values, (5) acceptance and disclosure, and (6) recognition of strengths and understanding of limitations.
Nested social groups within the social environment of a dementia care assisted living setting
Authors: Doyle Patrick J. , de Medeiros Kate , Saunders Pamela A.
Published: September 2011

The social environments of people with dementia are complex and still not fully understood. Investigating how residents in a dementia care setting navigate and participate within social groups is critical as the therapeutic benefits of social engagement are unequivocal. An ethnographic study of social environments within a dementia care residence revealed that there is active socialization and even strong and lasting friendships formed between people with dementia. Many of these relationships were observed to be a part of groups, ‘nested’ within the larger social environment. These ‘nested social groups’ had unique dynamics and their structuring was often influenced by outside factors (e.g. physical environment and staff preferences). The existence of these groups has implications for the experiences and quality of life of the residents in long-term care. Nested social groups will be defined and their function within the social environment will be discussed.
‘Perplexities of the rights of man’: Arendt on the aporias of human rights
Authors: Gündoğdu Ayten
Published: September 2011

This article provides a new interpretation of Hannah Arendt’s critical analysis of the ‘perplexities of the Rights of Man’ by drawing attention to its overlooked methodological orientations, especially its ‘aporetic’ nature. Arendt’s critique is aporetic as it centres on the paradoxes of human rights and analyses them by putting into practice a mode of inquiry that she associates with Socrates. The article challenges the conventional understanding of aporia as a paralysing impasse and suggests that aporetic thinking can create possibilities of rethinking key concepts especially in times of crises. To make this point, I respond to Jacques Rancière’s criticism that the paradoxes introduced by Arendt paralyse thinking and doom human rights to an inevitable destiny of failure. I argue that, precisely because of its aporetic nature, Arendt’s critique attends to possibilities of rethinking and reinventing human rights, as can be seen in her articulation of ‘a right to have rights’.
Measures of vibration exposure for a high-speed craft crew
Authors: Garme K , Burström L , Kuttenkeuler J
Published: September 2011

The paper compares measurement-based measures for human vibration exposure. Data were collected during sea trials on a 10 m, 50 kn coastguard craft equipped with a three-axial accelerometer at the coxswain seat and with vertically mounted gauges measuring the acceleration of the cockpit floor. The ISO 2631-1:1997 measures of vibration (namely the root-mean-square (r.m.s.) value of the whole-body vibration (determined from the frequency-weighted acceleration signal), the maximum transient vibration value (MTVV), and the vibration dose value), the ISO 2631-5:2004 measure (namely the daily equivalent static compression dose Sed), and also statistically based measures to evaluate the acceleration magnitude are compared and discussed with respect to their ability to identify the mitigating effect of the suspension seat and how the different measures rank the severity of the high-speed craft (HSC) ride. The paper concludes that the r.m.s. value and the MTVV are unsuitable for evaluation of the conditions aboard while the other investigated measures show potential in this respect. Further the approach of ISO 2631-5:2004 taking both the short-term and the long-term perspectives on the human exposure to vibration is concluded to be the most mature method well suited to evaluation of HSC conditions.
Apolipoprotein E-e4, Processing Speed, and White Matter Volume in a Genetically Enriched Sample of Midlife Adults
Authors: Ready Rebecca E. , Baran B. , Chaudhry M. , Schatz K. , Gordon J. , Spencer R. M. C.
Published: September 2011

Healthy midlife children of a parent with Alzheimer’s disease ([AD] N = 23; 9 male) participated in neuropsychological testing, and magnetic resonance imaging (MRI) of brain volumetrics were obtained. In all, 35% of the sample were apolipoprotein E (ApoE)-e4 positive (n = 8; 5 male). The ApoE-e4 group exhibited significantly slower performances on an executive function and processing speed measure and had less white matter volume than the non-ApoE-e4 group. Lesser white matter volume was significantly correlated with slower processing speed. Processing speed and changes in white matter volume might be indicators of preclinical decline in AD.
Listeria monocytogenes
Authors: Haroon Y. , Bhalla A. , El-Tahir A.
Published: September 2011

Infected aneurysms associated with Listeria monocytogenes are rare. We describe a case of an infrarenal abdominal aortic aneurysm infected by Listeria monocytogenes. The aneurysm was diagnosed using a contrast-enhanced computed tomography (CT) scan and the infective organism identified within positive blood cultures. The patient underwent a successful urgent open aortic aneurysm repair and completed a 6-week course of antibiotics.
Thoughts and Feelings About Organizational Change
Authors: Fugate Mel , Harrison Spencer , Kinicki Angelo J.
Published: September 2011

This longitudinal field study examines the relationships among the three focal constructs within appraisal theory—appraisal, emotion, and coping—at the beginning of change and their relationship with employee withdrawal at the end of an organizational restructuring. New theory is used to integrate past theory and research to propose and test a model containing synchronous reciprocal relationships between negative appraisal and negative emotions. Results confirmed a synchronous reciprocal relationship between negative appraisal and negative emotions, which suggests that appraisal is not a sequential process as often conceptualized and tested in the past. Negative appraisals and negative emotions also had negative relationships with control coping, which was negatively associated to intentions to quit, which in turn predicted subsequent voluntary turnover. This study thus extends appraisal theory and demonstrates it is a powerful alternative (theoretical) means for examining employee reactions to organizational change. Theoretical and practical implications of the results are discussed.
Animating the Photographic Trace, Intersecting Phantoms with Phantasms: Contemporary Media Arts, Digital Moving Pictures, and the Documentary’s ‘Expanded Field’
Authors: Kim Ji-Hoon
Published: September 2011

This article investigates the ways in which contemporary media artworks across various platforms provide a fresh look at the photographic inscription of reality by animating the still photograph with digitally produced movement. These artworks are based on what the author calls ‘digital moving pictures’, hybrid images in which photographic stillness and cinematic movement are interrelated in a single picture frame by the mediation of digital imaging systems. Examining the works of Jim Campbell, Ken Jacobs, David Claerbout, Julie Meltzer and David Thorne, the author argues that the pictures’ blurring of the boundaries between the live action and the animated images, and between the recorded and the manipulated, is meant to satisfy documentary epistephilia (a ‘desire to know’) and stimulate the viewer’s ‘pensive’ and ‘investigative’ engagements with the photographic trace as possible spectatorial modes of the documentary. The pictures then ask us to envision the documentary’s ‘expanded field’ (Rosalind Krauss), in which a series of binaries defining the modernist conception of the documentary are problematized, including prioritizing the photochemical qualities of analogue film and photography as directly guaranteeing evidential claims about their representations over the animated or graphically rendered image.
Equine Models of Articular Cartilage Repair
Authors: McIlwraith C. Wayne , Fortier Lisa A. , Frisbie David D. , Nixon Alan J.
Published: September 2011

Articular cartilage injuries of the knee and ankle are common, and a number of different methods have been developed in an attempt to improve their repair. Clinically, there are 2 distinct aims of cartilage repair: 1) restoration of joint function and 2) prevention or at least delay of the onset of osteoarthritis. These goals can potentially be achieved through replacement of damaged or lost articular cartilage with tissue capable of functioning under normal physiological environments for an extended period, but limitations of the final repair product have long been recognized and still exist today. Screening of potential procedures for human clinical use is done by preclinical studies using animal models. This article reviews equine chondral defect models that have been recently recognized to have specific advantages for translation into human articular cartilage regeneration. Defect models in the femoropatellar, femorotibial, and tibiotalar joints have been developed. The horse provides the closest approximation to humans in terms of articular cartilage and subchondral bone thickness, and it is possible to selectively leave the entire calcified cartilage layer or completely remove it. The defect on the equine medial femoral condyle emulates medial femoral condylar lesions in humans. Other advantages of the equine model include an ability to use an arthroscope to create lesions and perform second-look arthroscopies, the large lesion size allowing for more tissue for evaluation, and the ability to have controlled exercise and test the ability of the repair to cope with athletic exercise as well as institute rehabilitation regimens.
CCR6/CCR10-mediated plasmacytoid dendritic cell recruitment to inflamed epithelia after instruction in lymphoid tissues
Authors: Sisirak Vanja , Vey Nelly , Vanbervliet Béatrice , Duhen Thomas , Puisieux Isabelle , Homey Bernhard , Bowman Edward P. , Trinchieri Giorgio , Dubois Bertrand , Kaiserlian Dominique , Lira Sergio A. , Puisieux Alain , Blay Jean-Yves , Caux Christophe , Bendriss-Vermare Nathalie
Published: September 2011

Absent in peripheral tissues during homeostasis, human plasmacytoid dendritic cells (pDCs) are described in inflamed skin or mucosa. Here, we report that, unlike blood pDCs, a subset of tonsil pDCs express functional CCR6 and CCR10, and their respective ligands CCL20 and CCL27are detected in inflamed epithelia contacting blood dendritic cell antigen 2+ pDCs. Moreover, pDCs are recruited to imiquimod-treated skin tumors in WT but not CCR6-deficient mice, and competitive adoptive transfers reveal that CCR6-deficient pDCs are impaired in homing to inflamed skin tumors after intravenous transfer. On IL-3 culture, CCR6 and CCR10 expression is induced on human blood pDCs that become responsive to CCL20 and CCL27/CCL28, respectively. Interestingly, unlike myeloid DC, blood pDCs initially up-regulate CCR7 expression and CCL19 responsiveness on IL-3 ± CpG-B and then acquire functional CCR6 and CCR10. Finally, IL-3–differentiated CCR6+ CCR10+ pDCs secrete high levels of IFN-α in response to virus. Overall, we propose an unexpected pDCs migratory model that may best apply for mucosal-associated lymphoid tissues. After CCR7-mediated extravasation into lymphoid tissues draining inflamed epithelia, blood pDCs may be instructed to up-regulate CCR6 and/or CCR10 allowing their homing into inflamed epithelia (in mucosae or skin). At this site, pDCs can then produce IFN-α contributing to pathogen clearance and/or local inflammation.
Inducible knockout of GRP78/BiP in the hematopoietic system suppresses Pten-null leukemogenesis and AKT oncogenic signaling
Authors: Wey Shiuan , Luo Biquan , Tseng Chun-Chih , Ni Min , Zhou Hui , Fu Yong , Bhojwani Deepa , Carroll William L. , Lee Amy S.
Published: September 2011

Traditionally, GRP78 is regarded as protective against hypoxia and nutrient starvation prevalent in the microenvironment of solid tumors; thus, its role in the development of hematologic malignancies remains to be determined. To directly elucidate the requirement of GRP78 in leukemogenesis, we created a biallelic conditional knockout mouse model of GRP78 and PTEN in the hematopoietic system. Strikingly, heterozygous knockdown of GRP78 in PTEN null mice is sufficient to restore the hematopoietic stem cell population back to the normal percentage and suppress leukemic blast cell expansion. AKT/mTOR activation in PTEN null BM cells is potently inhibited by Grp78 heterozygosity, corresponding with suppression of the PI3K/AKT pathway by GRP78 knockdown in leukemia cell lines. This is the first demonstration that GRP78 is a critical effector of leukemia progression, at least in part through regulation of oncogenic PI3K/AKT signaling. In agreement with PI3K/AKT as an effector for cytosine arabinoside resistance in acute myeloid leukemia, overexpression of GRP78 renders human leukemic cells more resistant to cytosine arabinoside-induced apoptosis, whereas knockdown of GRP78 sensitizes them. These, coupled with the emerging association of elevated GRP78 expression in leukemic blasts of adult patients and early relapse in childhood leukemia, suggest that GRP78 is a novel therapeutic target for leukemia.
β-Lapachone induces heart morphogenetic and functional defects by promoting the death of erythrocytes and the endocardium in zebrafish embryos
Authors: Wu Yi-Ting , Lin Che Yi , Tsai Ming-Yuan , Chen Yi-Hua , Lu Yu-Fen , Huang Chang-Jen , Cheng Chao-Min , Hwang Sheng-Ping L
Published: September 2011

Background

β-Lapachone has antitumor and wound healing-promoting activities. To address the potential influences of various chemicals on heart development of zebrafish embryos, we previously treated zebrafish embryos with chemicals from a Sigma LOPAC1280™ library and found several chemicals including β-lapachone that affected heart morphogenesis. In this study, we further evaluated the effects of β-lapachone on zebrafish embryonic heart development.

Methods

Embryos were treated with β-lapachone or dimethyl sulfoxide (DMSO) at 24 or 48 hours post fertilization (hpf) for 4 h at 28°C. Heart looping and valve development was analyzed by whole-mount in situ hybridization and histological analysis. For fractional shortening and wall shear stress analyses, AB and Tg (gata1:DsRed) embryos were recorded for their heart pumping and blood cell circulations via time-lapse fluorescence microscopy. Dextran rhodamine dye injection into the tail reticular cells was used to analyze circulation. Reactive oxygen species (ROS) was analyzed by incubating embryos in 5-(and 6-)-chloromethyl-2',7'-dichloro-dihydrofluorescein diacetate (CM-H2DCFDA) and recorded using fluorescence microscopy. o-Dianisidine (ODA) staining and whole mount in situ hybridization were used to analyze erythrocytes. TUNEL assay was used to examine DNA fragmentation.

Results

We observed a linear arrangement of the ventricle and atrium, bradycardia arrhythmia, reduced fractional shortening, circulation with a few or no erythrocytes, and pericardial edema in β-lapachone-treated 52-hpf embryos. Abnormal expression patterns of cmlc2, nppa, BMP4, versican, and nfatc1, and histological analyses showed defects in heart-looping and valve development of β-lapachone-treated embryos. ROS production was observed in erythrocytes and DNA fragmentation was detected in both erythrocytes and endocardium of β-lapachone-treated embryos. Reduction in wall shear stress was uncovered in β-lapachone-treated embryos. Co-treatment with the NQO1 inhibitor, dicoumarol, or the calcium chelator, BAPTA-AM, rescued the erythrocyte-deficiency in circulation and heart-looping defect phenotypes in β-lapachone-treated embryos. These results suggest that the induction of apoptosis of endocardium and erythrocytes by β-lapachone is mediated through an NQO1- and calcium-dependent pathway.

Conclusions

The novel finding of this study is that β-lapachone affects heart morphogenesis and function through the induction of apoptosis of endocardium and erythrocytes. In addition, this study further demonstrates the importance of endocardium and hemodynamic forces on heart morphogenesis and contractile performance.
Invasive fungal sinusitis in patients with hematological malignancy: 15 years experience in a single university hospital in Taiwan
Authors: Chen Chien-Yuan , Sheng Wang-Huei , Cheng Aristine , Chen Yee-Chun , Tsay Woei , Tang Jih-Luh , Huang Shang-Yi , Chang Shan-Chwen , Tien Hwei-Fang
Published: September 2011

Background

Risk factors and outcomes in hematological patients who acquire invasive fungal sinusitis (IFS) are infrequently reported in the modern medical era.

Method

A retrospective study of hospitalized patients with hematological disease was conducted at National Taiwan University Hospital between January 1995 and December 2009.

Results

Clinical characteristics and outcomes with their associated radiographic and microbiological findings were analyzed. Forty-six patients with IFS and 64 patients with chronic non-invasive sinusitis were enrolled as comparsion. IFS developed more commonly in patients with acute myeloid leukemia (AML) and with prolonged neutropenia (absolute neutrophil count less than 500/mm3 for more than 10 days) (p < 0.001). Aspergillus flavus was the most common pathogen isolated (44%). Serum Aspergillus galactomannan antigen was elevated in seven of eleven patients (64%) with IFS caused by aspergillosis but negative for all three patients with mucormycosis. Bony erosion and extra-sinus infiltration was found in 15 of 46 (33%) patients on imaging. Overall, 19 of 46 patients (41.3%) died within 6 weeks. Patients with disease subtype of AML (p = 0.044; Odds Ratio [OR], 5.84; 95% confidence interval [95% CI], 1.02-30.56) and refractory leukemia status (p = 0.05; OR, 4.27; 95% CI, 1.003-18.15) had worse prognosis. Multivariate analysis identified surgical debridement as an independent good prognostic factor (p = 0.047) in patients with IFS.

Conclusions

Patients of AML with prolonged neutropenia (> 10 days) had significantly higher risk of IFS. Early introduction of anti-fungal agent and aggressive surgical debridement potentially decrease morbidity and mortality in high risk patients with IFS.
A case of bilateral self-induced keratoconus in a patient with tourette syndrome associated with compulsive eye rubbing: case report
Authors: Kandarakis Artemios , Karampelas Michael , Soumplis Vasileios , Panos Christos , Makris Nikolaos , Kandarakis Stylianos , Karagiannis Dimitrios
Published: September 2011

Background

Tourette syndrome is a neurologic disorder that is characterized by repetitive muscle contractions that produce stereotyped movements or sounds. Approximately 50% of individuals with TS also exhibit obsessive-compulsive behaviors including eye rubbing. We report a case of bilateral self-induced keratoconus in a patient with TS, associated with compulsive eye rubbing.

Case presentation

A 35-year-old man was first seen in our clinic as an outpatient due to rapid deterioration of vision in his right eye associated with pain and tearing, over a period of one month. Slit lamp biomicroscopy of the right eye showed a central stromal scar due to corneal hydrops. Clinical examination and corneal topography of the left eye were normal. Six months later the patient developed corneal hydrops of his left eye. During the following examinations his vision continued to deteriorate in both eyes, while a central stromal scar was forming in his left cornea. Four years after the initial examination the patient's visual acuity was no light perception in the right eye and counting fingers at 33 cm in the left eye. His right eye was phthisic.

Conclusions

Our patient developed a rapidly progressing bilateral corneal ectasia and phthisis of his right eye during a time period of 4 years. This unusual pattern suggests that the patient's compulsive behavior compromised both of his corneas and led to bilateral keratoconus.
Initial clinical experience with a novel vertebral augmentation system for treatment of symptomatic vertebral compression fractures: A case series of 26 consecutive patients
Authors: Korovessis Panagiotis , Repantis Thomas , Miller Larry E , Block Jon E
Published: September 2011

Background

Minimally invasive vertebral augmentation procedures are widely used to treat vertebral compression fractures although procedural polymethylmethacrylate cement leakage remains common. We report herein our initial experience with a novel vertebral augmentation technique designed to treat symptomatic vertebral osteoporotic fractures and osteolytic metastases with minimal cement extravasation.

Methods

Forty-two vertebral fractures were identified in 26 consecutive patients (mean age 74 ± 9 years). All patients were treated with a novel percutaneous vertebral augmentation device (Kiva® VCF Treatment System, Benvenue Medical, Santa Clara, CA, USA). Indications for surgery included recent (≤ 3 months) symptomatic osteoporotic vertebral fracture (n = 34) and pathologic vertebral fractures (e.g. metabolic bone disease, myeloma, metastasis) (n = 8) located between T10 and S1. Patient outcomes were evaluated pre-treatment and at 2- and 6-month follow-up visits. Postoperative cement extravasation was assessed with computed tomography. Patient-reported back pain was quantified using an 11-point numeric scale. Back-specific functional disability was self-reported with the Oswestry Disability Index on a 0 to 100% scale.

Results

No cases of intraoperative hypotension, respiratory disturbance, neurological deterioration, infection, or death were observed. There were 2 (4.8%) levels where anterior cement leakage was visible radiographically in patients with osteolyses. No intracanal leakage was observed. Back pain scores improved 71% (p < 0.001) from pre-treatment to the 6-month follow-up. Back function improved 56% from baseline to 6 months (p < 0.001).

Conclusions

The initial clinical experience with the Kiva® System demonstrated significant improvements in back pain and function with minimal and clinically insignificant procedural cement leakage.
Does Glycine max leaves or Garcinia Cambogiapromote weight-loss or lower plasma cholesterol in overweight individuals: a randomized control trial
Authors: Kim Ji-Eun , Jeon Seon-Min , Park Ki Hun , Lee Woo Song , Jeong Tae-Sook , McGregor Robin A , Choi Myung-Sook
Published: September 2011

Background

Natural food supplements with high flavonoid content are often claimed to promote weight-loss and lower plasma cholesterol in animal studies, but human studies have been more equivocal. The aim of this study was firstly to determine the effectiveness of natural food supplements containing Glycine max leaves extract (EGML) or Garcinia cambogia extract (GCE) to promote weight-loss and lower plasma cholesterol. Secondly to examine whether these supplements have any beneficial effect on lipid, adipocytokine or antioxidant profiles.

Methods

Eighty-six overweight subjects (Male:Female = 46:40, age: 20~50 yr, BMI > 23 < 29) were randomly assigned to three groups and administered tablets containing EGML (2 g/day), GCE (2 g/day) or placebo (starch, 2 g/day) for 10 weeks. At baseline and after 10 weeks, body composition, plasma cholesterol and diet were assessed. Blood analysis was also conducted to examine plasma lipoproteins, triglycerides, adipocytokines and antioxidants.

Results

EGML and GCE supplementation failed to promote weight-loss or any clinically significant change in %body fat. The EGML group had lower total cholesterol after 10 weeks compared to the placebo group (p < 0.05). EGML and GCE had no effect on triglycerides, non-HDL-C, adipocytokines or antioxidants when compared to placebo supplementation. However, HDL-C was higher in the EGML group (p < 0.001) after 10 weeks compared to the placebo group.

Conclusions

Ten weeks of EGML or GCE supplementation did not promote weight-loss or lower total cholesterol in overweight individuals consuming their habitual diet. Although, EGML did increase plasma HDL-C levels which is associated with a lower risk of atherosclerosis.
Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells
Authors: Yang Mei , Chen Jingqi , Su Fang , Yu Bin , Su Fengxi , Lin Ling , Liu Yujie , Huang Jian-Dong , Song Erwei
Published: September 2011

Background

Tumor-associated macrophages (TAMs) are alternatively activated cells induced by interleukin-4 (IL-4)-releasing CD4+ T cells. TAMs promote breast cancer invasion and metastasis; however, the mechanisms underlying these interactions between macrophages and tumor cells that lead to cancer metastasis remain elusive. Previous studies have found microRNAs (miRNAs) circulating in the peripheral blood and have identified microvesicles, or exosomes, as mediators of cell-cell communication. Therefore, one alternative mechanism for the promotion of breast cancer cell invasion by TAMs may be through macrophage-secreted exosomes, which would deliver invasion-potentiating miRNAs to breast cancer cells.

Results

We utilized a co-culture system with IL-4-activated macrophages and breast cancer cells to verify that miRNAs are transported from macrophages to breast cancer cells. The shuttling of fluorescently-labeled exogenous miRNAs from IL-4-activated macrophages to co-cultivated breast cancer cells without direct cell-cell contact was observed. miR-223, a miRNA specific for IL-4-activated macrophages, was detected within the exosomes released by macrophages and was significantly elevated in the co-cultivated SKBR3 and MDA-MB-231 cells. The invasiveness of the co-cultivated breast cancer cells decreased when the IL-4-activated macrophages were treated with a miR-223 antisense oligonucleotide (ASO) that would inhibit miR-223 expression. Furthermore, results from a functional assay revealed that miR-223 promoted the invasion of breast cancer cells via the Mef2c-β-catenin pathway.

Conclusions

We conclude that macrophages regulate the invasiveness of breast cancer cells through exosome-mediated delivery of oncogenic miRNAs. Our data provide insight into the mechanisms underlying the metastasis-promoting interactions between macrophages and breast cancer cells.
Abolished adherence alters signaling pathways in phorbol ester-induced human U937 cells
Authors: Otte Anna , Mandel Katharina , Reinstrom Gesche , Hass Ralf
Published: September 2011

Phorbol ester (TPA) treatment of human U937 myeloid leukemia cells is associated with increasing adherence and monocyte-like maturation whereby the role of β2 integrin-mediated attachment for subsequent growth properties and the differentiation program remains unclear. Here, stably-transfected U937 cells with a pMTH1 vector containing the β2 integrin gene of CD11b in antisense orientation (asCD11b-U937) demonstrated a significantly reduced proliferative capacity in contrast to control vector transfectants (pMTH1-U937) or wild-type U937 cells. Phorbol ester exposure induced adherence and growth arrest in more than 90% of pMTH1-U937 and wild-type U937 cells after 72 h. In contrast, TPA-treated asCD11b-U937 failed to attach and the proliferation continued in more than 30% of the cells. Moreover, increased apoptosis appeared in asCD11b-U937 after TPA induction in contrast to pMTH1-U937 cells. In addition, non-specific inhibition of adherence on an agarose surface demonstrated internucleosomal DNA fragmentation in both, pMTH1-U937 and asCD11b-U937 after TPA treatment indicating a functional relationship between abolished adherence, regulation of proliferation and induction of apoptosis. Western blot analysis revealed differences in the expression levels and altered phosphorylation patterns of Pyk-2, pp60src and p42/p44 MAP kinases between pMTH1-U937 and asCD11b-U937 following TPA exposure which was also substantiated by Pyk-2 immunoprecipitation. These findings suggested that induced adherence predominantly mediated by a functional CD11b/CD18 integrin in U937 cells is involved in the activation of downstream signaling kinases and contributes to cell cycle regulation and apoptosis during monocytic maturation.
Different patterns of NF-κB and Notch1 signaling contribute to tumor-induced lymphangiogenesis of esophageal squamous cell carcinoma
Authors: Su Chunhua , Chen Zhenguang , Luo Honghe , Su Yihua , Liu Wangkai , Cai Lie , Wang Tao , Lei Yiyan , Zhong Beilong
Published: September 2011

Background

Lymph node involvement and tumor-induced lymphangiogenesis appear as the earliest features of esophageal squamous cell carcinoma (ESCC), although the molecular regulatory mechanisms involved have remained unclear. Our aim was to investigate the contribution of NF-κB and Notch1 signaling to lymph node involvement and tumor-induced lymphangiogenesis in ESCC.

Material and methods

NF-κB and Notch1 expression in 60 tissue samples of ESCC were assessed by immunohistochemical staining. The correlations of NF-κB and Notch1 with lymph node involvement, lymphatic vessel density (LVD), podoplanin, and vascular endothelial growth factor-C (VEGF-C) were further evaluated to determine the association of NF-κB and Notch1 expression with tumor-induced lymphangiogenesis.

Results

Chi-square tests revealed that NF-κB and Notch1 expression in ESCC tissues were significant associated with lymph node metastasis, LVD, podoplanin, and VEGF-C expression. Strong expression of NF-κB, but weak expression of Notch1, was observed in tumor tissues with lymph nodes involvement (P< 0.05 for both). The mean histoscores of LVD, podoplanin, and VEGF-C staining were higher in high-NF-κB-expressing tissue than in low-expressing tissue (P< 0.05 for each). In contrast, the mean histoscores of LVD and VEGF-C staining were lower in high-Notch1-expressing tissue than in low-expressing tissue (P< 0.05 for both). A multiple factors analysis of LVD and VEGF-C further demonstrated that LVD and VEGF-C status were significantly correlated with NF-κB and Notch1 expression in tumors. NF-κB and Notch1 expression were also significantly inversely correlated (P< 0.05).

Conclusion

These results suggest that different patterns of NF-κB and Notch1 signaling contribute to lymph nodes metastasis and tumor-induced lymphangiogenesis of ESCC, and reveal that up-regulation of NF-κB is associated with down-regulation of Notch1 in tumor tissue.
erbB3 recruitment of insulin receptor substrate 1 modulates insulin-like growth factor receptor signalling in oestrogen receptor-positive breast cancer cell lines
Authors: Knowlden Janice M , Gee Julia MW , Barrow Denise , Robertson John F , Ellis Ian O , Nicholson Robert I , Hutcheson Iain R
Published: September 2011

Introduction

Recently we reported that insulin receptor substrate 1 (IRS-1), classically an adaptor protein for the insulin-like growth factor type I receptor (IGF-IR), associates with the epidermal growth factor receptor in oestrogen receptor (ER)-positive (ER+) tamoxifen-resistant breast cancer cells. In this study, we examined whether IRS-1 also associates with another erbB receptor family member, erbB3, and what impact this might have on IGF-IR signalling in three ER+ breast cancer cell lines.

Methods

Immunoprecipitation and Western blot analysis were utilised to examine the potential association between erbB3 and IRS-1 in MCF-7, T47D and BT-474 cells in the absence and presence of the erbB3/4 ligand heregulin β1 (HRGβ1). Subsequently, the impact of a selective IGF-IR/IR inhibitor 4-anilino-5-bromo-2-[4-(2-hydroxy-3-(N, N-dimethylamino)propoxy)anilino]pyrimidine on this association and HRGβ1 signalling was assessed in these cell lines. Immunohistochemical analysis of a small cohort of ER+ breast cancer patient samples was also performed to determine the potential clinical relevance of this novel interaction.

Results

Immunoprecipitation and Western blot analysis revealed an interaction between erbB3 and IRS-1 in MCF-7, T47D and BT-474 cells, with HRGβ1 significantly enhancing this recruitment and promoting IRS-1 phosphorylation at Y612. IRS-1 participates in erbB3 signalling in MCF-7 and T47D cells as IRS-1 knockdown impaired HRGβ1 signalling. Importantly, recruitment of IRS-1 by erbB3 reduced IRS-1 association with IGF-IR in MCF-7 and T47D cells, whilst blockade of IGF-IR-enhanced erbB3-IRS-1 interaction and sensitised both cell lines to HRGβ1, allowing HRGβ1 to override IGF-IR blockade. Consequently, suppression of IRS-1 signalling enhanced the effects of IGF-IR inhibition in these cells. This novel interaction may have clinical relevance, as immunohistochemical analysis of a small ER+ breast tumour series revealed significant positive correlations between phosphorylated IRS-1 Y612 expression and total erbB3, phosphorylated Akt and Ki-67 expression.

Conclusions

IRS-1 can be recruited to IGF-IR and erbB3 in ER+ breast cancer cells, and this provides an adaptive resistance mechanism when these receptors are targeted individually. Consequently, cotargeting IGF-IR and either erbB3 or IRS-1 should prove to be a more effective strategy for the treatment of ER+ breast cancer.
Therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells after intrathecal administration by lumbar puncture in a rat model of cerebral ischemia
Authors: Lim Jung Yeon , Jeong Chang Hyun , Jun Jin Ae , Kim Seong Muk , Ryu Chung Heon , Hou Yun , Oh Wonil , Chang Jong Wook , Jeun Sin-Soo
Published: September 2011

Introduction

Stem cell transplantation is a promising therapeutic strategy for the treatment of stroke. Mesenchymal stem cells (MSCs) are a potential cell source for clinical application because they can be easily obtained and cultivated with a high proliferative capacity. The safety and efficacy of cell therapy depends on the mode of cell administration. To determine the therapeutic potential of intrathecal administration of MSCs by lumbar puncture (LP), we administrated human umbilical cord blood-derived MSCs (hUCB-MSCs) intrathecally into the lumbar spinal cord or intravenously into the tail vein in a rat model of stroke, and then investigated whether hUCB-MSCs could enter the brain, survive, and improve post-stroke neurological functional recovery.

Methods

hUCB-MSCs (1.0 × 106) were administrated three days after stroke induced by occlusion of the middle cerebral artery. The presence of hUCB-MSCs and their survival and differentiation in the brain tissue of the rats was examined by immunohistochemistry. Recovery of coordination of movement after administration of hUCB-MSCs was examined using a Rotarod test and adhesive-removal test on the 7th, 14th, 21st, and 28th days after ischemia. The volume of ischemic lesions seven days after the experimental procedure was evaluated using 2-3-5-triphenyltetrazolium (TTC) staining.

Results

Rats receiving hUCB-MSCs intrathecally by LP had a significantly higher number of migrated cells within the ischemic area when compared with animals receiving cells intravenously. In addition, many of the cells administered intrathecally survived and a subset of them expressed mature neural-lineage markers, including the mature neuron marker NeuN and glial fibrillary acidic protein, typical of astrocytes. Animals that received hUCB-MSCs had significantly improved motor function and reduced ischemic damage when compared with untreated control animals. Regardless of the administration route, the group treated with 1 × 106 hUCB-MSCs showed better neurological recovery, without significant differences between the two treatment groups. Importantly, intrathecal administration of 5 × 105 hUCB-MSCs significantly reduced ischemic damage, but not in the intravenously treated group. Furthermore, the cells administered intrathecally survived and migrated into the ischemic area more extensively, and differentiated significantly into neurons and astrocytes.

Conclusions

Together, these results indicate that intrathecal administration of MSCs by LP may be useful and feasible for MSCs treatment of brain injuries, such as stroke, or neurodegenerative disorders.
Cannabis, COMT and psychotic experiences
Authors: Zammit Stanley , Owen Michael J. , Evans Jonathan , Heron Jon , Lewis Glyn
Published: September 2011

Background

A putative interaction between cannabis and variation at rs4680 within the catechol-methyl-transferase (COMT) gene on psychosis has been reported, but not adequately replicated.

Aims

To examine whether the relative risk of developing psychosis following use of cannabis is dependent upon variation within COMT.

Method

A longitudinal study of 2630 individuals from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort who completed questionnaire-based assessments for cannabis use at age 14 and incident psychotic experiences at age 16. Six SNPs within COMT were genotyped.

Results

There was no evidence of an interaction under multiplicative models between cannabis use and COMT on the risk of developing psychotic experiences in our primary analyses. In sensitivity analyses we observed highly variable evidence of interaction, whereby psychotomimetic effects of cannabis were greater in methionine homozygotes under some scenarios, but in valine homozygotes under others.

Conclusions

Cannabis increases risk of psychosis irrespective of underlying COMT genotypes. These findings argue against the widely held belief that the relative risk of developing psychosis following use of cannabis is dependent upon variation within COMT. The public health message about the potential increase in risk of psychotic disorders following cannabis use should not be tempered by reports that this harm is subgroup specific in the absence of robust evidence of replication.
An Inevitable Moment for America
Authors: Sestak Joe
Published: September 2011

The rebellions across the Middle East and North Africa provide a perspective for America about its own leaders, who have made the “politics of survival” the determining factor of what they do. The loss of faith in our traditional political institutions caused by their focus on self-aggrandizing power instead of needed change for our people gives impetus to outside forces — such as the Tea Party — much as in Tunisia and Egypt. Leaders must restore Americans’ trust by a commitment to accountability and results if they are to be the ones to lead the restoration of the American Dream.
Overcoming anoikis – pathways to anchorage-independent growth in cancer
Authors: Guadamillas Marta C. , Cerezo Ana , del Pozo Miguel A.
Published: September 2011

Anoikis (or cell-detachment-induced apoptosis) is a self-defense strategy that organisms use to eliminate ‘misplaced’ cells, i.e. cells that are in an inappropriate location. Occasionally, detached or misplaced cells can overcome anoikis and survive for a certain period of time in the absence of the correct signals from the extracellular matrix (ECM). If cells are able to adapt to their new environment, then they have probably become anchorage-independent, which is one of the hallmarks of cancer cells. Anoikis resistance and anchorage-independency allow tumor cells to expand and invade adjacent tissues, and to disseminate through the body, giving rise to metastasis. Thus, overcoming anoikis is a crucial step in a series of changes that a tumor cell undergoes during malignant transformation.

Tumor cells have developed a variety of strategies to bypass or overcome anoikis. Some strategies consist of adaptive cellular changes that allow the cells to behave as they would in the correct environment, so that induction of anoikis is aborted. Other strategies aim to counteract the negative effects of anoikis induction by hyperactivating survival and proliferative cascades. The recently discovered processes of autophagy and entosis also highlight the contribution of these mechanisms to rendering the cells in a dormant state until they receive a signal initiated at the ECM, thereby circumventing anoikis. In all situations, the final outcome is the ability of the tumor to grow and metastasize. A better understanding of the mechanisms underlying anoikis resistance could help to counteract tumor progression and prevent metastasis formation.
The regulation of abscission by multi-protein complexes
Authors: Neto Hélia , Gould Gwyn W.
Published: September 2011

The terminal stage of cytokinesis – a process termed abscission – is the severing of the thin intercellular bridge that connects the two daughter cells. Recent work provides new insight into the mechanism by which this microtubule-dense membrane bridge is resolved, and highlights important roles for multi-protein assemblies in different facets of abscission. These include the endosomal sorting complex required for transport (ESCRT), which appears to have a decisive role in the final scission event, and vesicle tethering complexes, which potentially act at an earlier stage, and might serve to prepare the abscission site. Here, we review recent studies of the structure, function and regulation of these complexes as related to abscission. We focus largely on studies of cytokinesis in mammalian cells. However, cell division in other systems, such as plants and Archae, is also considered, reflecting the mechanistic conservation of membrane-scission processes during cell division.
WDR36 acts as a scaffold protein tethering a G-protein-coupled receptor, Gαq and phospholipase Cβ in a signalling complex
Authors: Cartier Andréane , Parent Audrey , Labrecque Pascale , Laroche Geneviève , Parent Jean-Luc
Published: September 2011

We identified the WD-repeat-containing protein, WDR36, as an interacting partner of the β isoform of thromboxane A2 receptor (TPβ) by yeast two-hybrid screening. We demonstrated that WDR36 directly interacts with the C-terminus and the first intracellular loop of TPβ by in vitro GST-pulldown assays. The interaction in a cellular context was observed by co-immunoprecipitation, which was positively affected by TPβ stimulation. TPβ–WDR36 colocalization was detected by confocal microscopy at the plasma membrane in non-stimulated HEK293 cells but the complex translocated to intracellular vesicles following receptor stimulation. Coexpression of WDR36 and its siRNA-mediated knockdown, respectively, increased and inhibited TPβ-induced Gαq signalling. Interestingly, WDR36 co-immunoprecipitated with Gαq, and promoted TPβ–Gαq interaction. WDR36 also associated with phospholipase Cβ (PLCβ) and increased the interaction between Gαq and PLCβ, but prevented sequestration of activated Gαq by GRK2. In addition, the presence of TPβ in PLCβ immunoprecipitates was augmented by expression of WDR36. Finally, disease-associated variants of WDR36 affected its ability to modulate Gαq-mediated signalling by TPβ. We report that WDR36 acts as a new scaffold protein tethering a G-protein-coupled receptor, Gαq and PLCβ in a signalling complex.
ThePOF1Bcandidate gene for premature ovarian failure regulates epithelial polarity
Authors: Padovano Valeria , Lucibello Ilaria , Alari Valentina , Della Mina Pamela , Crespi Arianna , Ferrari Ilaria , Recagni Marta , Lattuada Donatella , Righi Marco , Toniolo Daniela , Villa Antonello , Pietrini Grazia
Published: September 2011

POF1B is a candidate gene for premature ovarian failure (POF); it is mainly expressed in polarised epithelial tissues, but its function in these tissues and the relationship with the disorder are unknown. Here we show colocalisation of POF1B with markers of both adherens and tight junctions in human jejunum. The tight junction localisation was maintained by the human POF1B stably expressed in the MDCK polarised epithelial cell line, whereas it was lost by the POF1B R329Q variant associated with POF. Localisation of apico-basal polarity markers and ultrastructure of the tight junctions were maintained in cells expressing the mutant. However, tight junction assembly was altered, cells were dysmorphic and the monolayer organisation was also altered in three-dimensional culture systems. Moreover, cells expressing the POF1B R329Q variant showed defects in ciliogenesis and cystogenesis as a result of misorientation of primary cilia and mitotic division. All of these defects were explained by interference of the mutant with the content and organisation of F-actin at the junctions. A role for POF1B in the regulation of the actin cytoskeleton was further verified by shRNA silencing of the endogenous protein in human intestinal Caco-2 cells. Taken together, these data indicate that localisation of POF1B to tight junctions has a key role in the organisation of epithelial monolayers by regulating the actin cytoskeleton.