scholarly journals Akt/PKB enhances non-canonical Wnt signals by compartmentalizing β-Catenin

2017 ◽  
Author(s):  
Nicolas Aznar ◽  
Nina Sun ◽  
Ying Dunkel ◽  
Jason Ear ◽  
Matthew D. Buschman ◽  
...  
Keyword(s):  
Cellular Proliferation ◽  
Colony Growth ◽  
Akt Pathway ◽  
Cell Contact ◽  
Long Distance ◽  
Recycling Endosomes ◽  
Dynein Motor ◽  
Canonical Wnt ◽  
The Impact ◽  
E Cadherin

AbstractCellular proliferation is antagonistically regulated by canonical and non-canonical Wnt signals; their dysbalance triggers cancers. It is widely believed that the PI3-K→ Akt pathway enhances canonical Wnt signals by affecting transcriptional activity and stability of β-catenin. Here we demonstrate that the PI3-K→Akt pathway also enhances non-canonical Wnt signals by compartmentalizing β-catenin. By phosphorylating the phosphoinositide(PI)-binding domain of a multimodular signal transducer, Daple, Akt abolishes Daple’s ability to bind PI3-P-enriched endosomes that engage dynein motor complex for long-distance trafficking of β-catenin/E-cadherin complexes to pericentriolar recycling endosomes (PCREs). Phosphorylation compartmentalizes Daple/β-catenin/E-cadherin complexes to cell-cell contact sites, enhances non-canonical Wnt signals, and thereby, suppresses colony growth. Dephosphorylation compartmentalizes β-catenin on PCREs, a specialized compartment for prolonged unopposed canonical Wnt signaling, and enhances colony growth. Cancer-associated Daple mutants that are insensitive to Akt mimic a constitutively dephosphorylated state. This work not only identifies Daple as a platform for crosstalk between Akt and the non-canonical Wnt pathway, but also reveals the impact of such crosstalk during cancer initiation and progression.

scholarly journals A Daple-Akt feed-forward loop enhances noncanonical Wnt signals by compartmentalizing β-catenin

2017 ◽  
Vol 28 (25) ◽  
pp. 3709-3723 ◽  
Author(s):  
Nicolas Aznar ◽  
Nina Sun ◽  
Ying Dunkel ◽  
Jason Ear ◽  
Matthew D. Buschman ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Cross Talk ◽  
Cellular Proliferation ◽  
Wnt Signaling Pathway ◽  
Colony Growth ◽  
Cell Contact ◽  
Long Distance ◽  
Canonical Wnt ◽  
The Impact ◽  
E Cadherin

Cellular proliferation is antagonistically regulated by canonical and noncanonical Wnt signals; their dysbalance triggers cancers. We previously showed that a multimodular signal transducer, Daple, enhances PI3-K→Akt signals within the noncanonical Wnt signaling pathway and antagonistically inhibits canonical Wnt responses. Here we demonstrate that the PI3-K→Akt pathway serves as a positive feedback loop that further enhances noncanonical Wnt signals by compartmentalizing β-catenin. By phosphorylating the phosphoinositide- (PI) binding domain of Daple, Akt abolishes Daple’s ability to bind PI3-P-enriched endosomes that engage dynein motor complex for long-distance trafficking of β-catenin/E-cadherin complexes to pericentriolar recycling endosomes (PCREs). Phosphorylation compartmentalizes Daple/β-catenin/E-cadherin complexes to cell–cell contact sites, enhances noncanonical Wnt signals, and thereby suppresses colony growth. Dephosphorylation compartmentalizes β-catenin on PCREs, a specialized compartment for prolonged unopposed canonical Wnt signaling, and enhances colony growth. Cancer-associated Daple mutants that are insensitive to Akt mimic a constitutively dephosphorylated state. This work not only identifies Daple as a platform for cross-talk between Akt and the noncanonical Wnt pathway but also reveals the impact of such cross-talk on tumor cell phenotypes that are critical for cancer initiation and progression.

Cell-to-cell contact influences proliferative marker expression and apoptosis in MIN6 cells grown in islet-like structures

2005 ◽  
Vol 288 (3) ◽  
pp. E502-E509 ◽  
Author(s):  
Melanie J. Luther ◽  
Emma Davies ◽  
Dany Muller ◽  
Moira Harrison ◽  
Adrian J. Bone ◽  
...  
Keyword(s):  
Cellular Proliferation ◽  
Kinase Inhibitors ◽  
Three Dimensional ◽  
Cell Aggregation ◽  
Cell Interactions ◽  
Cell Phenotype ◽  
Cell Contact ◽  
Min6 Cells ◽  
Primary Mouse ◽  
E Cadherin

Cell-to-cell interactions play an important role in the development and maintenance of the β-cell phenotype. Here, we have investigated whether E-cadherin plays a role in regulating the growth of insulin-secreting MIN6 cells configured as three-dimensional islet-like clusters (pseudoislets). Pseudoislets form by cell aggregation rather than by proliferation from individual cells and attain the size of primary mouse islets after ∼7 days of maintenance in culture. E-cadherin is known to mediate homotypic cell adhesion between β-cells and has also been implicated in a number of cellular processes, including proliferation, apoptosis, and differentiation. E-cadherin and its associated intracellular elements, α- and β-catenin, were upregulated in MIN6 pseudoislets. Pseudoislet formation was associated with an increased expression of cyclin-dependent kinase inhibitors and a concomitant downregulation of Ki67, suggesting an overall reduction in cellular proliferation. However, measurements of 5-bromo-2′-deoxyuridine incorporation revealed that there were no differences in the rate of MIN6 cell proliferation whether they were configured as monolayers or as pseudoislets, which is likely to be a result of their being a transformed cell line. Cells within pseudoislets were not necrotic, but apoptosis appeared to be upregulated in the islet-like structures. However, no differential expression of Fas and FasL was detected in monolayers and pseudoislets. These results suggest that cell-to-cell interactions within islet-like structures may initiate antiproliferative and proapoptotic signals.

The Impact of Cell-Cell Contact, E-Cadherin and EGF Receptor on the Cellular Radiosensitivity of A431 Cancer Cells

2012 ◽  
Vol 178 (3) ◽  
pp. 224-233 ◽  
Author(s):  
Ercole Mazzeo ◽  
Stephanie Hehlgans ◽  
Vincenzo Valentini ◽  
Michael Baumann ◽  
Nils Cordes
Keyword(s):  
Cancer Cells ◽  
Egf Receptor ◽  
Cell Contact ◽  
Cellular Radiosensitivity ◽  
The Impact ◽  
E Cadherin ◽  
Cell Cell

scholarly journals Cleavage of E-Cadherin by Matrix Metalloproteinase-7 Promotes Cellular Proliferation in Nontransformed Cell Lines via Activation of RhoA

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Conor C. Lynch ◽  
Tracy Vargo-Gogola ◽  
Lynn M. Matrisian ◽  
Barbara Fingleton
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Epithelial Cell ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Migration And Invasion ◽  
Cell Contact ◽  
E Cadherin ◽  
Cell Cell

Perturbations in cell-cell contact machinery occur frequently in epithelial cancers and result in increased cancer cell migration and invasion. Previously, we demonstrated that MMP-7, a protease implicated in mammary and intestinal tumor growth, can process the adherens junction component E-cadherin. This observation leads us to test whether MMP-7 processing of E-cadherin could directly impact cell proliferation in nontransformed epithelial cell lines (MDCK and C57MG). Our goal was to investigate the possibility that MMP-7 produced by cancer cells may have effects on adjacent normal epithelium. Here, we show that MMP-7 processing of E-cadherin mediates, (1) loss of cell-cell contact, (2) increased cell migration, (3) a loss of epithelial cell polarization and (4) increased cell proliferation via RhoA activation. These data demonstrate that MMP-7 promotes epithelial cell proliferation via the processing of E-cadherin and provide insights into the molecular mechanisms that govern epithelial cell growth.

Novel Method of Laser Direct Writing for Precise Patterning of Human Dermal Fibroblasts

2010 ◽  
Author(s):  
Nathan R. Schiele ◽  
Douglas B. Chrisey ◽  
David T. Corr
Keyword(s):  
Cellular Proliferation ◽  
Dermal Fibroblasts ◽  
Growth Surface ◽  
Cell Contact ◽  
Direct Write ◽  
Human Dermal Fibroblasts ◽  
Direct Writing ◽  
Laser Direct Writing ◽  
Patterning Technique ◽  
The Impact

The ability to control a cell’s location, pattern geometry, and proximity to neighboring cells, in vitro, is highly desired to gain insight into cell-cell interactions, such as the modes of cellular signaling (direct cell contact, paracrine, or endocrine). A laser-based cell patterning technique, laser direct write, enables the precise spatial placement of living cells, with all the advantages of CAD/CAM control [1]. However, this technique is limited in usefulness due to the dependence on Matrigel® (BD Biosciences, Bedford, MA). The growth factor constituents of Matrigel® may interfere with many cellular processes under investigation and may preclude or greatly limit the utility of laser direct writing for precise cell cultures [2]. Therefore, to address this limitation, the objective of this study was to develop a Matrigel®-free laser direct writing method. Through the use of customized gelatin coatings on both the ribbon and receiving substrate, we effectively adapted the direct write technique to precisely pattern cells without the use of Matrigel®, as demonstrated with human dermal fibroblasts. The gelatin partially encapsulates the trypsinized cells on the ribbon, providing a volitization zone to protect the cells, and on the receiving substrate cushions the impact of transfer while maintaining moisture. Gelatin liquefies at 37°C, which allows it to be removed from the growth surface ensuring cellular proliferation, uninhibited by growth surface treatments. This represents a fundamental change from the original direct write technique in which cells must first form initial attachments to the ribbon via Matrigel® and then are written to a Matrigel® coated receiving substrate for their sustained growth. Additionally, we have developed a method to monitor the location of the patterned cells post-transfer to show that a gelatin coated-receiving substrate is effective as a patterning surface and ensures the registry of the pattern until cell attachment, even after the gelatin has been removed with the first growth medium application. This precise patterning technique can now be used in many biomedical applications, including those that involve cell types highly sensitive to growth factors, such as stem cells and cancer cells.

The methodological approach for the determination of the pressure of artificial raindrops as a question of the theory of splash soil erosion

2020 ◽  
pp. 24-28
Author(s):  
Mihail Zver'kov
Keyword(s):  
Block Diagram ◽  
Methodological Approach ◽  
Control Measures ◽  
Soil Conditions ◽  
Effective Pressure ◽  
Long Distance ◽  
Splash Erosion ◽  
Rain Drops ◽  
Artificial Rain ◽  
The Impact

To the article the results of the theoretical and experimental researches are given on questions of estimates of the dynamic rate effect of raindrop impact on soil. The aim of this work was to analyze the current methods to determine the rate of artificial rain pressure on the soil for the assessment of splash erosion. There are the developed author’s method for calculation the pressure of artificial rain on the soil and the assessment of splash erosion. The study aims to the justification of evaluation methods and the obtaining of quantitative characteristics, prevention and elimination of accelerated (anthropogenic) erosion, the creation and the realization of the required erosion control measures. The paper considers the question of determining the pressure of artificial rain on the soil. At the moment of raindrops impact, there is the tension in the soil, which is called vertical effective pressure. It is noted that the impact of rain drops in the soil there are stresses called vertical effective pressure. The equation for calculation of vertical effective pressure is proposed in this study using the known spectrum of raindrops. Effective pressure was 1.4 Pa for the artificial rain by sprinkler machine «Fregat» and 5.9 Pa for long distance sprinkler DD-30. The article deals with a block diagram of the sequence for determining the effective pressure of rain drops on the soil. This diagram was created by the author’s method of calculation of the effective pressure of rain drops on the soil. The need for an integrated approach to the description of the artificial rain impact on the soil is noted. Various parameters characterizing drop erosion are considered. There are data about the mass of splashed soil in the irrigation of various irrigation machinery and installations. For example, the rate (mass) of splashed soil was 0.28…0.78 t/ha under irrigation sprinkler apparatus RACO 4260–55/701C in the conditions of the Ryazan region. The method allows examining the environmental impact of sprinkler techniques for analyzes of the pressure, caused by raindrops, on the soil. It can also be useful in determining the irrigation rate before the runoff for different types of sprinkler equipment and soil conditions.

DISCRESSION OF THE SAMPLE RESORTS POLICE IN THE IMPLEMENTATION OF ADMINISTRATIVE LAW PERSPECTIVE INVESTIGATION

2020 ◽  
Vol 4 (2) ◽  
pp. 147
Author(s):  
Tamrin Muchsin ◽  
Sri Sudono Saliro ◽  
Nahot Tua Parlindungan Sihaloho ◽  
Sardjana Orba Manullang
Keyword(s):  
Empirical Research ◽  
Qualitative Method ◽  
Government Regulation ◽  
Sampling Technique ◽  
Administrative Law ◽  
Criminal Investigation ◽  
Accurate Data ◽  
Long Distance ◽  
The Impact ◽  
Depth Interviews

It is still found that investigating officers do not have an S1 degree or equivalent in thejurisdiction of the Sambass Resort Police as mandated in PP No. 58 of 2010 concerningAmendments to Government Regulation Number 27 of 1983 concerning theImplementation of KUHAP article 2A paragraph (1) letter a. If the requirements ofinvestigators are not fulfilled, there will automatically be limits of authority, includingthe inability to issue investigation orders, detention warrants and other administrativeletters. This study used a qualitative method with juridical empirical research. Toobtain accurate data, purposive sampling technique was used, and primary datacollection by conducting in-depth interviews. The research results found, among others:first, discretion regarding the administration of investigations in the jurisdiction of theSambas Resort Police for the Sambas District Police who do not have investigatingofficers who meet the requirements, is then taken over by the Head of the CriminalInvestigation Unit as the supervisor of the integrated criminal investigation function.Second, the impact of an integrated investigation administration causes the time tocarry out investigations to be slow due to the long distance between the Sector Policeand the Resort Police.

45. Education at distance: Broadcasting ECG rounds to Southeastern Ontario (BESO Project). An innovative approach for teaching electrocardiography

2007 ◽  
Vol 30 (4) ◽  
pp. 51 ◽  
Author(s):  
A. Baranchuk ◽  
G. Dagnone ◽  
P. Fowler ◽  
M. N. Harrison ◽  
L. Lisnevskaia ◽  
...  
Keyword(s):  
Health Care ◽  
Real Time ◽  
Digital Signal ◽  
Teaching Methodology ◽  
Care Providers ◽  
Long Distance ◽  
Medicine Clerkship ◽  
Time Problem ◽  
The Impact ◽  
Ecg Interpretation

Electrocardiography (ECG) interpretation is an essential skill for physicians as well as for many other health care professionals. Continuing education is necessary to maintain these skills. The process of teaching and learning ECG interpretation is complex and involves both deductive mechanisms and recognition of patterns for different clinical situations (“pattern recognition”). The successful methodologies of interactive sessions and real time problem based learning have never been evaluated with a long distance education model. To evaluate the efficacy of broadcasting ECG rounds to different hospitals in the Southeastern Ontario region; to perform qualitative research to determine the impact of this methodology in developing and maintaining skills in ECG interpretation. ECG rounds are held weekly at Kingston General Hospital and will be transmitted live to Napanee, Belleville, Oshawa, Peterborough and Brockville. The teaching methodology is based on real ECG cases. The audience is invited to analyze the ECG case and the coordinator will introduce comments to guide the case through the proper algorithm. Final interpretation will be achieved emphasizing the deductive process and the relevance of each case. An evaluation will be filled out by each participant at the end of each session. Videoconferencing works through a vast array of internet LANs, WANs, ISDN phone lines, routers, switches, firewalls and Codecs (Coder/Decoder) and bridges. A videoconference Codec takes the analog audio and video signal codes and compresses it into a digital signal and transmits that digital signal to another Codec where the signal is decompressed and retranslated back into analog video and audio. This compression and decompression allows large amounts of data to be transferred across a network at close to real time (384 kbps with 30 frames of video per second). Videoconferencing communication works on voice activation so whichever site is speaking has the floor and is seen by all the participating sites. A continuous presence mode allows each site to have the same visual and audio involvement as the host site. A bridged multipoint can connect between 8 and 12 sites simultaneously. This innovative methodology for teaching ECG will facilitate access to developing and maintaining skills in ECG interpretation for a large number of health care providers. Bertsch TF, Callas PW, Rubin A. Effectiveness of lectures attended via interactive video conferencing versus in-person in preparing third-year internal medicine clerkship students for clinical practice examinations. Teach Learn Med 2007; 19(1):4-8. Yellowlees PM, Hogarth M, Hilty DM. The importance of distributed broadband networks to academic biomedical research and education programs. Acad Psychaitry 2006;30:451-455

scholarly journals The Effect of Repeated Whole-Body Cryotherapy on Sirt1 and Sirt3 Concentrations and Oxidative Status in Older and Young Men Performing Different Levels of Physical Activity

Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 37
Author(s):  
Gabriela Wojciak ◽  
Jadwiga Szymura ◽  
Zbigniew Szygula ◽  
Joanna Gradek ◽  
Magdalena Wiecek
Keyword(s):  
Physical Activity ◽  
Young Men ◽  
Oxidative Status ◽  
Whole Body ◽  
Stress Index ◽  
Blood Levels ◽  
Long Distance ◽  
Antioxidant Defence ◽  
Whole Body Cryotherapy ◽  
The Impact

Background: The activity of antioxidant enzymes and sirtuins (Sirt) decreases along with age, which is counteracted by aerobic training. Sirtuins increase antioxidant defence. Whole-body cryotherapy (WBC) increases total antioxidant capacity (TAC) in young men. The aim of our study was to assess the impact of 24 WBC treatments on the blood concentration of selected sirtuins and the level of antioxidant defence as well as oxidative stress index of training and non-training men depending on age. Methods: The study involved 40 males. In each group, there were 10 non-training older and young men (60 NTR and 20 NTR), and 10 older and young long-distance runners (60 TR, 20 TR). During an 8-week period, participants underwent 24 WBC treatments (3 min −130 °C), which were performed three times a week (Monday, Wednesday, Friday). The concentrations of Sirt1, Sirt3, TAC, total oxidative status and the activity of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) in the blood were determined before 1 WBC and after 1 WBC, 12 WBC and 24 WBC. Results: After 1 WBC, the activity of GPx and the concentration of Sirt1 and TAC in 60 TR and TAC in 60 NTR increased. After 12 WBC, the level of Sirt1 in 20 NTR and SOD in 20 TR increased. After 24 WBC, the level of Sirt1 increased in 60 TR and in 20 NTR, Sirt3 in 60 TR and SOD in 20 TR. Conclusions: Cryogenic temperatures increase blood levels of Sirt1 and Sirt3 and systemic antioxidant defence in men, but the effect is dependent on age, level of performed physical activity and the number of applied treatments.

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