CELL POLARITY REGULATES ORGAN GROWTH THROUGH THE HIPPO PATHWAY

Defects in apical-basal cell polarity and abnormal expression of cell polarity determinants are linked to human cancer. Loss of polarity is highly correlated with malignancy. In Drosophila, perturbation of apical-basal polarity, including overexpressing the apical determinant Crumbs, can lead to uncontrolled tissue growth. Cells mutant for the basolateral determinant scribble overproliferate and can form neoplastic tumors. Interestingly, scribble mutant clones that arise in wild-type tissues are eliminated and therefore do not manifest their tumorigenic potential. However, the mechanisms by which cell polarity coordinates with growth control pathways in developing organs to achieve appropriate organ size remain obscure. To investigate the function of apical determinants in growth regulation, I investigated the mechanism by which the apical determinant Crumbs affects growth in Drosophila imaginal discs. I found that crumbs gain and loss of function cause overgrowth and induction of Hippo target genes. In addition, Crumbs is required for the proper localization of Expanded, an upstream component of the Hippo pathway. Furthermore, we uncoupled the cell polarity and growth control function of Crb through structure-functional analysis. Taken together, our data identify a role of Crb in growth regulation specifically through modulation of the Hippo pathway. To further explore the role of polarity in growth control, I investigated how cells mutant for basolateral determinants are eliminated by using patches of cells mutant for scribble (scribble mutant clones) as a model system. We found that competitive cell-cell interactions eliminate tumorigenic scribble cells by modulation of the Hippo pathway. The regulation of Hippo signaling is required and sufficient to restrain the tumorous growth of scribble mutant cells. Artificially increasing the relative fitness of scribble mutant cells unleashes their tumorigenic potential. Therefore, we have identified a novel tumor-suppression mechanism that depends on signaling between normal and tumorigenic cells. These data identify evasion of cell competition as a critical step toward malignancy and illustrate a role for wild-type tissue in eliminating abnormal cells and preventing the formation of tumors

Magnetowave Induced Plasma Wakefield Acceleration for Ultra High Energy Cosmic Rays

Magnetowave induced plasma wakefield acceleration (MPWA) in a relativistic astrophysical outflow has been proposed as a viable mechanism for the acceleration of cosmic particles to ultra high energies. Here we present simulation results that clearly demonstrate the viability of this mechanism for the first time. We invoke the high frequency and high speed whistler mode for the driving pulse. The plasma wakefield so induced validates precisely the theoretical prediction. We show that under appropriate conditions, the plasma wakefield maintains very high coherence and can sustain high-gradient acceleration over a macroscopic distance. Invoking gamma ray burst (GRB) as the source, we show that MPWA production of ultra high energy cosmic rays (UHECR) beyond ZeV 10^21 eV is possible.Comment: 4 pages, 4 figure

ACTION RESEARCH INTO E-LEARNING CURICULUM DEVELOPMENT FOR LIBRARY AND INFORMATION SCIENCE IN TAIWAN

Introduction. E-learning is flourishing in higher education due to its ability to lift time and place restrictions from teaching and learning, giving those who do not have time to be full-time on-campus students an opportunity to receive professional education. Because many library staff have not received professional education, more e-learning curricula and programs by Library and Information Science schools is something that many libraries in Taiwan look forward to. Facing demand for e-learning from library staff, the Graduate Institute of Library, Information and Archival Studies (LIAS) at National Cheng-Chi University undertook an experimental curriculum project . Method. The purpose of this study was to develop an e-learning master's program with six e-learning curricula for library staff and instructors in senior high schools in accordance with quality assurance mechanism .The study was conducted as action research with five stages as follows: (a) describing the problem and its focus; (b) exploring some action options for the problem; (c)seeking collaborative partners and discussing; (d)undertaking action options: the five lecturers of the LIAS planned and developed six e-learning courses with web-based learning systems; (f) evaluation and feedback: six courses were modified according to student learning outcome assessments and course reviews. Conclusion. In addition to describing the planning and implementation of the curriculum, the article also reviews the effectiveness of e-learning teaching and learning, as well as offering final conclusions and recommendations

Tumor Suppression by Cell Competition Through Regulation of the Hippo Pathway

Homeostatic mechanisms can eliminate abnormal cells to prevent diseases such as cancer. However, the underlying mechanisms of this surveillance are poorly understood. Here we investigated how clones of cells mutant for the neoplastic tumor suppressor gene scribble (scrib) are eliminated from Drosophila imaginal discs. When all cells in imaginal discs are mutant for scrib, they hyperactivate the Hippo pathway effector Yorkie (Yki), which drives growth of the discs into large neoplastic masses. Strikingly, when discs also contain normal cells, the scrib− cells do not overproliferate and eventually undergo apoptosis through JNK-dependent mechanisms. However, induction of apoptosis does not explain how scrib− cells are prevented from overproliferating. We report that cell competition between scrib− and wild-type cells prevents hyperproliferation by suppressing Yki activity in scrib− cells. Suppressing Yki activation is critical for scrib− clone elimination by cell competition, and experimental elevation of Yki activity in scrib−cells is sufficient to fuel their neoplastic growth. Thus, cell competition acts as a tumor-suppressing mechanism by regulating the Hippo pathway in scrib− cells. Animals have evolved homeostatic mechanisms to eliminate abnormal and cancerous cells, protecting the animal from harm (1). A prominent example of an organism removing abnormal cells that have the potential to form tumors is the elimination of scribble mutant (scrib−) cells from Drosophila imaginal discs (2–8). scrib is a conserved tumor-suppressor gene that is essential for the establishment of apical–basal cell polarity (8–10). Scrib is a scaffold protein that localizes to basolateral cell junctions and functions together with the Discs large (Dlg) and Lethal giant larvae (Lgl) adaptor proteins to govern apical–basal cell polarity in epithelial cells (8, 10). Imaginal discs from Drosophila larvae that are homozygous mutant for scrib, dlg, or lgl grow into large tumorous masses of neoplastic cells that display several hallmarks of carcinomas: They lose apical–basal cell polarity, hyperproliferate, and have defects in differentiation (10). Interestingly, the neoplastic phenotype of scrib− cells depends on their cellular environment. When scrib− cells are produced in patches (clones) of mutant cells that are surrounded by normal cells, they do not hyperproliferate, remain small, and eventually are eliminated (2–7, 11–13). Similar effects are observed for lgl− and dlg− clones, although they may not be eliminated very efficiently (11, 14, 15). Thus, the presence of wild-type cells prevents scrib−, lgl−, and dlg−cells from manifesting their tumorigenic potential (2–7, 11–15). Several groups have shown that the JNK stress–response pathway is activated in scrib− clones, leading to engulfment and death or extrusion of mutant cells from the epithelium (2–4, 6, 11, 16). Activation of JNK is required for the elimination of scrib− cells because blocking JNK activity in scrib−cells results in massive overgrowth of clones that is reminiscent of the tumorous overgrowth of entirely mutant discs (2–4, 6, 12, 13). However, blocking apoptosis does not cause overproliferation of scrib− clones (2, 3). Therefore, in addition to inducing apoptosis, JNK suppresses the potential of scrib− cells to hyperproliferate (2, 3). However, how scrib−cells are prevented from hyperproliferating is not known. The presence of normal cells is required for the elimination of tumorigenic scrib− clones because genetically ablating the normal tissue surrounding scrib− cells results in hyperproliferation of the scrib− cells (2, 3). It has been suggested that cell competition, a process by which viable cells of lower fitness are removed from a tissue and replaced through extra proliferation of fitter neighbors (17), is responsible for the elimination of scrib−and lgl− cell clones (2, 14). However, the hypothesis that scrib− and lgl− clones are eliminated by cell competition is in conflict with other reports and thus is controversial. It has been reported that cells with compromised Scrib or Lgl function exhibit elevated activity of Yorkie (Yki), a transcriptional coactivator and downstream effector of the Hippo growth-control pathway (13, 14, 18–20). The Hippo pathway is a conserved tumor-suppressor pathway that suppresses growth by antagonizing the activity of Yki (21). Thus, loss of Hippo pathway activity or elevated levels of Yki activity result in hyperproliferation of imaginal disc cells and resistance to apoptosis that normally would eliminate extra cells (21). Notably, an increase in Yki activity can rescue weak cells, such as cells heterozygous for Minute (M) mutations, from being eliminated by cell competition (22). M mutations occur in ribosomal protein-encoding genes and were the first class of genes identified as having cell-competition phenotypes (23). Homozygous M mutations are lethal, but heterozygous Manimals are viable, although their cells have reduced growth rates (23). In genetic mosaics, however, interaction between wild-type and M+/− cells leads to the elimination of the M+/−cells and expansion of the wild-type population, a phenomenon termed “cell competition” (17). Thus, M+/− cells are less competitive than wild-type cells. Importantly, elevated levels of Yki can rescue M+/− cells from being eliminated by cell competition and also can transform normal cells into supercompetitors that induce apoptosis in their neighbors and proliferate at their neighbors’ expense (22, 24, 25). Yki may increase the competitiveness of cells by inducing the expression of Myc, a known regulator of cell competition (24–27). However, the reports that scrib− cells have high levels of Yki activity and the hypothesis that scrib− cells are eliminated by cell competition present a paradox. If scrib− cells indeed have elevated levels of Yki activity, why does that elevated Yki activity not protect scrib−cells from cell competition? Here we investigated this paradox further. We show that scrib− cells are indeed eliminated by cell competition. We found that for this elimination to occur, scrib− cells undergo a JNK-dependent suppression of Yki activity; this suppression of Yki activity prevents scrib− cells from hyperproliferating and enables their removal. The modulation of Yki activity in scrib−cells thus is a critical effect of the JNK-dependent cell-competition process that removes such tumorigenic cells from imaginal discs. Finally we show that the Myc and Ras oncogenes, which can rescue scrib− clones from elimination (2, 4, 15), do so by conferring competitive fitness to scrib− cells and thereby prevent the down-regulation of Yki activity in scrib− cells. Our results thus further characterize the effects of cell-competition pathways in removing tumorigenic scrib− cells from imaginal discs

Cost-effectiveness of Clinical Pathway in Coronary Artery Bypass Surgery

Few studies have been devoted to the exploration of the effect of clinical pathways on coronary artery diseases treated with coronary artery bypass (CAB) surgery. This study was aimed to investigate the cost and effectiveness of the clinical pathway on CAB surgery in a medical center. With a retrospective dataset in 2003-2007, 212 CAB surgery patients were included. Data of the costs and postoperative complication occurrence and length of stays were the focus and patient demographics, surgical risk indicator EuroSCORE, surgical conditions were collected. It revealed that there was differentiation across specified cost items in beating heart CAB surgery patients, but not for heart arrest CAB surgery patients with and without clinical pathways enrolled. In addition, there was no difference in postoperative complication occurrence in CAB surgery patients enrolled into clinical pathways. However, robotic beating heart CAB surgery patients enrolled clinical pathways were shown to have less postoperative ordinary ward stay than those not enrolled clinical pathways. CAB surgery patients' age and surgical risks were related to their postoperative lengths of stay to some extent

Effect of Auricular Acupressure on Peri- and Early Postmenopausal Women with Anxiety: A Double-Blinded, Randomized, and Controlled Pilot Study

We tested effects of auricular acupressure on peri- and early postmenopausal women with anxiety (PPWA). Fifty PPWA were randomly assigned to the auricular acupressure group (AG) or the sham group (SG). After 3 meals and before sleep every day for 4 weeks, the AG received auricular acupressure on the bilateral ear shenmen and subcortex points for 3 min per point on alternating ears. The SG received sham auricular acupressure. The Alprazolam was reduced from 0.5 mg/day at baseline to 0.3 mg/day 4 weeks after auricular acupressure (4 W) in the AG (P < .05) whereas maintained at 0.5 mg/day in the SG (P > .05). The Zolpidem was reduced from 3.0 mg/day at baseline to 1.5 mg/day at 4 W (P < .05) whereas was reduced from 2.4 mg/day to 1.9 mg/day at 4 W in the SG (P > .05), thus, significant tapering medication, suggesting auricular acupressure is helpful to PPWA

The Effects of Hunger Marketing in Scarcity products

[[abstract]]Hunger marketing is a marketing strategy where goods suppliers deliberately limit product supply to achieve excess demand. This research paper primarily investigated the varying impacts of Jordon shoes (tangible goods) and travelling to the Maldives (intangible goods) on the variables of the various dimensions of hunger marketing. This researchalso focused on the relationships between hunger marketing; knowledge exchange motivation, opportunities, and ability; involvement; epistemic value; purchase intention; WOM; and the interference caused by Jordon shoes, travelling to the Maldives, and financial status. This research adopted structural equation modelling (SEM) to construct the research framework. The researchers collaborated with a survey company to distribute the questionnaires, of which 975 were recovered. The analytical methods were employed to verify the collected data such as factor loading, t-value, AVE, Cronbach’s α being consistent with the hypotheses set by the aims of this research. The results showed could provide academic value in hunger marketing related researches.[[notice]]補正完

A 78-Year-Old Woman with Fecaloid Vaginal Discharge

A 78-year-old woman with a history of colon cancer with metastasis to the liver was presented to our emergency department because of bilateral groin pain and difficulty in walking, which had gradually increased during the previous 5 days. The pain was of sudden onset, radiating to the back, without aggravating or relieving factors. It was associated with constipation, dysuria and vaginal discharge. She reported passing fecal matter from the vagina one month ago. On physical examination, she appeared malnourished. Her blood pressure was 98/65 mmHg, with a 108 beats/min heart rate and 28 breaths/min respiratory rate. She was afebrile. Physical examinations were unremarkable, except for pale conjunctiva, abdominal distention, and diffuse tenderness especially over the umbilicus with guarding tenderness. Bowel sounds were decreased. Pelvic examination showed a yellowish odorous vaginal discharge from the external orifice of uterus. A complete blood cell count showed the following: leukocyte count, 34,200/mm3; segmented neutrophils, 87.5%; hemoglobin level of 7.4 mg/dl; hematocrit, 18.8%; and platelet, 180000/uL. Other laboratory studies included: glucose, 86 mg/dL; serum urea nitrogen, 28 mg/dL; serum creatinine, 0.87 mg/dL; sodium, 142 mEq/L; potassium, 4.8 mEq/L; albumin, 2.5g/dL; a carbohydrate antigen 19-9 level of 3,244 U/ml, and a carcinoembryonic antigen (CEA) level of 64.6 ng/ml. Coronal and axial cuts of patient’s abdominopelvic computed Tomography (CT) are shown in figures 1 and 2