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This antibody showed diffuse staining for YAP within the cytosol and nuclei, but, noticeably, it showed intense staining of the nucleoli of LPCs. This staining was non-specific, as shRNA treatment of cells abolished YAP expression to undetectable levels by Western blot yet the nucleolar staining remained. Similar spurious YAP nucleolar staining was also seen in mouse embryonic fibroblasts and mouse liver tissue, indicating that this antibody is unsuitable for immunological applications to determine YAP sub-cellular localisation in mouse cells or tissues.
Interestingly nucleolar staining was not evident in D cells suggesting the antibody may be suitable for use in human cells.
Given the large body of published work on YAP in recent years, many of which utilise this antibody, this study raises concerns regarding its use for determining sub-cellular localisation. From a broader perspective, it serves as a timely reminder of the need to perform appropriate controls to ensure the validity of published data.
Arsenic-induced cutaneous hyperplastic lesions are associated with the dysregulation of Yap , a Hippo signaling-related protein. However, the mechanism of these alterations remains elusive. Here, we provide novel observations that arsenic induced Hippo signaling pathway in the murine skin.
This pathway plays crucial roles in determining organ size during the embryonic development and if aberrantly activated in adults, contributes to the pathogenesis of epithelial neoplasm. However, in arsenic-treated epidermis, we did not observed its inactivation. Thus, as expected, unphosphorylated- Yap was translocated to the nucleus in arsenic-treated epidermis. Yap by binding to the transcription factors TEADs induces transcription of its target genes.
Consistently, an up-regulation of Yap -dependent target genes Cyr61, Gli2, Ankrd1 and Ctgf was observed in the skin of arsenic-treated mice. These data provide evidence that arsenic-induced canonical Hippo signaling pathway and Yap -mediated disruption of tight and adherens junctions are independently regulated. These effects together may contribute to the carcinogenic effects of arsenic in the skin.
The general mechanism underlying the tumor suppressor activity of the Hippo signaling pathway remains unclear. In this study, we explore the molecular mechanisms connecting the Hippo signaling pathway with glucose metabolism. The inhibition of lactate production and cellular proliferation induced by shikonin also depends on the Hippo pathway activity. In summary, regulation of glucose metabolism could serve as a new tumor suppressor mechanism orchestrated by the Hippo signaling pathway.
Topographic and sedimentary features in the Yap subduction zone and their implications for the Caroline Ridge subduction. The Yap subduction zone in the western Pacific presents some unique features compared to normal intra-oceanic subduction zones such as the subduction of an oceanic plateau. However, due to the relative paucity of geophysical data, the detailed structure remains unknown in this area. In this study, we present the latest high-quality swath bathymetry and multi-channel seismic data acquired synchronously in across the Yap subduction zone.
The topographic and sedimentary features are intensively investigated and a modified evolutionary model of the Yap subduction zone is proposed. Our seismic data clearly reveal landslide deposits at the upper slope break of the forearc, to the north of the Yap Island, which was identified as the fault notch denoting a lithological boundary in previous work.
The swath bathymetry and seismic profile reveal detailed horst and graben structures, including a crescent-shaped fault zone near the contact between the Yap Trench and the Caroline Ridge. A simple geometric model is proposed to explain the structure formation, indicating that the higher topography of the Caroline Ridge resulted in enhanced bending-related extension.
A seismic angular unconformity named R1 is identified in the Sorol Trough, marking the onset of rifting in the trough. A modified model for the Yap subduction zone evolution is proposed, incorporating three major tectonic events: the proto- Yap Arc rupture in the Oligocene, the collision of the Caroline Ridge and the Yap Trench in the late Oligocene or middle Miocene, and the onset of the Sorol Trough rifting in the late Miocene.
Full Text Available The extracellular environment possesses a rich milieu of biophysical and biochemical signaling cues that are simultaneously integrated by cells and influence cellular phenotype. Yes-associated protein YAP and transcriptional co-activator with PDZ-binding motif WWTR1; TAZ, two important signaling molecules of the Hippo pathway, have been recently implicated as nuclear relays of cytoskeletal changes mediated by substratum rigidity and topography.
These proteins intersect with other important intracellular signaling pathways e. In the cornea, epithelial cells adhere to the stroma through a 3-dimensional topography-rich basement membrane, with features in the nano-submicron size-scale that are capable of profoundly modulating a wide range of fundamental cell behaviors.
Results presented in this study reflect the complexities underlying the molecular relationships between the cytoskeleton, growth factors, heat shock proteins, and co-activators of transcription that impact mechanotransduction.
Our results show that the transcriptional coactivator yes-associated protein 1 YAP 1 , which is the oncogenic component of the Hippo signaling pathway, is elevated in the stem-like cells from NSCLC and contributes to their self-renewal and ability to form angiogenic tubules. These effects of YAP 1 were mediated through the embryonic stem cell transcription factor, Sox2. The binding of Oct4 to YAP 1 could be detected in cell lines as well as tumor tissues; the interaction was elevated in NSCLC samples compared to normal tissue as seen by proximity ligation assays.
YAP 1 bound to Oct4 through the WW domain, and a peptide corresponding to this region could disrupt the interaction.
Delivery of the WW domain peptide to stem-like cells disrupted the interaction and abrogated Sox2 expression, self-renewal, and vascular mimicry. Depleting YAP 1 reduced the expression of multiple epithelial-mesenchymal transition genes and prevented the growth and metastasis of tumor xenografts in mice; overexpression of Sox2 in YAP 1 null cells rescued these functions. These results demonstrate a novel regulation of stem-like functions by YAP 1, through the modulation of Sox2 expression.
Radon gamma-ray spectrometry with YAP :Ce scintillator. In particular, the application to radon and radon-daughters gamma-ray spectrometry was investigated. The crystal response has been studied under severe extreme conditions to simulate environments of geophysical interest, particularly those found in geothermal and volcanic areas. Tests in water up to a temperature of deg. The measurements with standard radon sources provided by the National Institute for Metrology of Ionizing Radiations ENEA have emphasized the non-hygroscopic properties of the scintillator and a small dependence of the light yield on temperature and HNO sub 3.
The data collected in this first step of our research have pointed out that the YAP :Ce scintillator can allow high response stability for rad Activation of the oxidative stress regulator Pp Yap 1 through conserved cysteine residues during methanol metabolism in the yeast Pichia pastoris. The methylotrophic yeast Pichia pastoris can grow on methanol as sole source of carbon and energy. The first reaction in yeast methanol metabolism, catalyzed by an abundant peroxisomal enzyme, alcohol oxidase, generates high levels of H 2 O 2 , but the oxidative stress response during methanol metabolism has not been elucidated.
In this study, we isolated the Yap 1 homolog of P. The Pp Yap 1 transcription factor is activated after exposure to various reactive agents, and therefore functions as a regulator of the redox system in P. This study is the first demonstration of a yeast Yap 1 family protein activated during conventional metabolism. Self-mode-locking operation of a diode-end-pumped Tm: YAP laser with watt-level output power.
Without any additional mode-locking elements in the cavity, stable and self-starting mode-locking operation has been realized. The maximum average output power is as high as 1. Randazzo, N. Sofia, I Catania Italy ], E-mail: nunzio. Tests were performed to investigate the possibility of using this detector as a proton calorimeter. The size of the crystal was chosen so that the proton energy is totally lost inside the medium.
The authors propose to use the YAP Ce crystal in medical applications for proton therapy. In particular, in proton computed tomography pCT project it is necessary as a calorimeter in order to measure the proton residual energy after the phantom. The crystal performances confirm that the YAP Ce crystal represents a good solution for these kinds of application. The first structure of a protein—phosphopeptide complex is reported at 1. The YAP binding motif is revealed for the first time using crystallographic tools.
The proteins are a class of eukaryotic acidic adapter proteins, with seven isoforms in humans. They are involved in pivotal pathways in the cell such as signal transduction, gene expression, enzyme activation, cell division and apoptosis. By transducing signals from the cytoplasm to the nucleus, YAP is important for transcriptional regulation. In both variants, interaction with proteins after phosphorylation of Ser is important for nucleocytoplasmic trafficking, via which the localization of YAP is controlled.
Normal hematopoietic stem cell function in mice with enforced expression of the Hippo signaling effector YAP 1. Full Text Available The Hippo pathway has recently been implicated in the regulation of organ size and stem cells in multiple tissues. The transcriptional cofactor yes-associated protein 1 Yap 1 is the most downstream effector of Hippo signaling and is functionally repressed by the upstream components of the pathway.
Overexpression of YAP 1 stimulates proliferation of stem and progenitor cells in many tissues, consistent with inhibition of Hippo signaling. To study the role of Hippo signaling in hematopoietic stem cells HSCs, we created a transgenic model with inducible YAP 1 expression exclusively within the hematopoietic system.
Following 3 months induction, examination of blood and bone marrow in the induced mice revealed no changes in the distribution of the hematopoietic lineages compared to control mice. Moreover, the progenitor cell compartment was unaltered as determined by colony forming assays and immunophenotyping. To address whether YAP 1 affects the quantity and function of HSCs we performed competitive transplantation experiments.
We show that ectopic YAP 1 expression does not influence HSC function neither during steady state nor in situations of hematopoietic stress. This is in sharp contrast to effects seen on stem- and progenitor cells in other organs and suggests highly tissue specific functions of the Hippo pathway in regulation of stem cells.
YAP scintillators for resonant detection of epithermal neutrons at pulsed neutron sources. Tardocchi, M. Recent studies indicate the resonance detector RD technique as an interesting approach for neutron spectroscopy in the electron volt energy region.
This work summarizes the results of a series of experiments where RD consisting of YAlO 3 YAP scintillators were used to detect scattered neutrons with energy in the range eV.
These measurements showed that a significant improvement in the signal-to-background ratio can be achieved by setting a lower level discrimination on the pulse height at about keV equivalent photon energy. Response to arsenic stress in Saccharomyces cerevisiae is orchestrated by the regulatory protein Yap 8, which mediates transcriptional activation of ACR2 and ACR3. This study contributes to the state of art knowledge of the molecular mechanisms underlying yeast stress response to arsenate as it provides the genetic and biochemical evidences that Yap 8, through cysteine residues , , and , is the sensor of presence of arsenate in the cytosol.
Moreover, it is here reported for the first time the essential role of the Mediator complex in the transcriptional activation of ACR2 by Yap 8. Based on our data, we propose an order-of-function map to recapitulate the sequence of events taking place in cells injured with arsenate. The Mediator complex then transfers the regulatory signals conveyed by Yap 8 to the core transcriptional machinery, which culminates with TBP occupancy, ACR2 upregulation and cell adaptation to arsenate stress.
Temperature influence on spectroscopic properties and 2. The spectroscopic and laser properties of Er: YAP crystal, that is appropriate for generation at 2.
The sample of Er: YAP 1 at. During experiments the Er: YAP was attached to temperature controlled copper holder and it was placed in vacuum chamber. The transmission and emission spectra together with the fluorescence decay time were measured depending on temperature.
The Er: YAP crystal was longitudinally pumped by radiation from laser diode that works in pulse regime repetition rate Laser resonator was hemispherical, mm in length with flat pumping mirror HR 2. In pulsed regime, the highest slope efficiency with respect to absorbed mean power was 1. The maximum output of mean power was 3.
The maximal output power 27 mW with slope efficiency up to 3. The radiation generated by Er: YAP laser 2. The energy of gammas from the electron—positron annihilation processes keV is also included in the study. The atom displacements distributions inside each material are calculated following the Monte Carlo assisted Classical Method introduced by the authors. This procedure also allows to study the atom displacements in-depth distributions inside each crystal.
The atom displacements damage in LYSO crystals is found to be higher than in Lu YAP crystals, mainly provoked by the displacements of silicon and oxygen atoms. On the other hand, the correlation between the atom displacements and energy deposition in-depth distributions is excellent. The atom displacements to energy deposition ratio is found to increases with more energetic photon sources. However, the molecular events underlying these GNAQ-driven malignancies are not yet defined, thus limiting the ability to develop cancer-targeted therapies.
Here, we focused on the transcriptional coactivator YAP , a critical component of the Hippo signaling pathway that controls organ size. Characterization and management of the commercial sector of the Pohnpei coral reef fishery, Micronesia. More than species were represented during surveys, with 25 species very common or common within combined-gear catch. Acanthurids contributed the greatest to catch volume, with bluespine unicornfish, Naso unicornis, and orangespine unicornfish, Naso lituratus, among the most frequently observed herbivores.
Nighttime spearfishing was the dominant fishing method and inner lagoon areas were primarily targeted. A seasonal sales ban March April , intended to reduce pressure on reproductively active serranids, significantly increased the capture volume of other families.
Catch was significantly greater during periods of low lunar illumination, suggesting higher fishing success or greater effort, or both.
The marketed catch was dominated by juveniles and small adults, based on fishes of known size at sexual maturity. Artificially depressed market prices appear to be catalyzing potential or realized overfishing by increasing the volume of fish needed to offset rising fuel prices. These results support the need for comprehensive fisheries management that produces sustainable fishing and marketing practices and promotes shared management and enforced responsibilities between communities and the state.
To be effective, management should prohibit nighttime spearfishing. Slunga, E. The time constants and intensities of the two components of the YAP :Ce signal were measured, as were the time constant and intensity of the weak component of the slow part of the BaF 2 signal.
Furthermore, the dependence of the light yield on the particle energy has been investigated for both BaF 2 and YAP :Ce.
WW domains of the yes-kinase-associated-protein YAP transcriptional regulator behave as independent units with different binding preferences for PPxY motif-containing ligands. Full Text Available YAP is a WW domain-containing effector of the Hippo tumor suppressor pathway, and the object of heightened interest as a potent oncogene and stemness factor.
YAP has two major isoforms that differ in the number of WW domains they harbor. Elucidating the degree of co-operation between these WW domains is important for a full understanding of the molecular function of YAP. We present here a detailed biophysical study of the structural stability and binding properties of the two YAP WW domains aimed at investigating the relationship between both domains in terms of structural stability and partner recognition. We have carried out a calorimetric study of the structural stability of the two YAP WW domains, both isolated and in a tandem configuration, and their interaction with a set of functionally relevant ligands derived from PTCH1 and LATS kinases.
We find that the two YAP WW domains behave as independent units with different binding preferences, suggesting that the presence of the second WW domain might contribute to modulate target recognition between the two YAP isoforms. Analysis of structural models and phage-display studies indicate that electrostatic interactions play a critical role in binding specificity. Together, these results are relevant to understand of YAP function and open the door to the design of highly specific ligands of interest to delineate the functional role of each WW domain in YAP signaling.
Few specimens of water mites have been collected from Pacific Island streams, especially higher elevation, head water streams. Mutations in Adenomatous polyposis coli APC underlie familial adenomatous polyposis FAP , an inherited cancer syndrome characterized by the widespread development of colorectal polyps.
Whether other effector pathways mediate APC’s tumor suppressor function is less clear. Here we report that activation of YAP , the downstream effector of the Hippo signaling pathway, is a general hallmark of tubular adenomas from FAP patients. We show that APC functions as a scaffold protein that facilitates the Hippo kinase cascade by interacting with Sav1 and Lats1.
The solid state reaction method was used to prepare YAP powder or ceramic pellets. DTA method was applied for examination of the phase crystallization in the tested system. X-ray diffraction method XRD was used for characterization of the phase composition. X-ray microanalysis EDS was used to control homogeneity in the small areas.
Morphology of the resultant samples are presented on SEM pictures. The results show a significant influence of the starting powders on the homogeneity, purity and temperature of formation of the main phase.
With an incident diode power of Prenatal exposure to dietary fat induces changes in the transcriptional factors, TEF and YAP , which may stimulate differentiation of peptide neurons in rat hypothalamus. Full Text Available Gestational exposure to a high-fat diet HFD stimulates the differentiation of orexigenic peptide-expressing neurons in the hypothalamus of offspring. To examine possible mechanisms that mediate this phenomenon, this study investigated the transcriptional factor, transcription enhancer factor-1 TEF, and co-activator, Yes-associated protein YAP , which when inactivated stimulate neuronal differentiation.
This was accompanied by increased density and fluorescence intensity of ENK neurons. Genetic knockdown of TEF or YAP stimulated ENK expression in hypothalamic neurons, supporting a close relationship between these transcription factors and neuropeptide. Coral skeletal tin and copper concentrations at Pohnpei , Micronesia: possible index for marine pollution by toxic anti-biofouling paints.
We present 40 year-long skeletal chronologies of tin Sn and copper Cu from an annually-banded coral Porites sp. Both the elements are present in antifouling marine paints and are released inadvertently into ambient seawater. Especially, Sn has often been used in the form of tributyltin TBT.
Based on a stepwise pretreatment examination, Sn and Cu both inside and outside the aragonite lattice of the coral skeleton show a potential for providing marine pollution indicators.
However, a significant decrease in both the ratios in the beginning of s can be attributed to regulation of the use of TBT on cargo ships by countries such as the USA, Japan and Australia. LIX1 regulates YAP 1 activity and controls the proliferation and differentiation of stomach mesenchymal progenitors.
Smooth muscle cell SMC plasticity maintains the balance between differentiated SMCs and proliferative mesenchymal progenitors, crucial for muscular tissue homeostasis. Studies on the development of mesenchymal progenitors into SMCs have proven useful in identifying molecular mechanisms involved in digestive musculature plasticity in physiological and pathological conditions.
Here, we show that Limb Expression 1 LIX1 molecularly defines the population of mesenchymal progenitors in the developing stomach. Using in vivo functional approaches in the chick embryo, we demonstrate that LIX1 is a key regulator of stomach SMC development. However, as stomach development proceeds, sustained LIX1 expression has a negative impact on further SMC differentiation and this is associated with a decrease in YAP 1 activity.
We demonstrate that expression of LIX1 must be tightly regulated to allow fine-tuning of the transcript levels and state of activation of the pro-proliferative transcriptional coactivator YAP 1 to regulate proliferation rates of stomach mesenchymal progenitors and their differentiation.
Our data highlight dual roles for LIX1 and YAP 1 and provide new insights into the regulation of cell density-dependent proliferation, which is essential for the development and homeostasis of organs. The role of the Yap 5 transcription factor in remodeling gene expression in response to Fe bioavailability. Full Text Available The budding yeast Saccharomyces cerevisiae has developed several mechanisms to avoid either the drastic consequences of iron deprivation or the toxic effects of iron excess.
In this work, we analysed the global gene expression changes occurring in yeast cells undergoing iron overload. Several genes directly or indirectly involved in iron homeostasis showed altered expression and the relevance of these changes are discussed. Microarray analyses were also performed to identify new targets of the iron responsive factor Yap 5. Besides the iron vacuolar transporter CCC1, Yap 5 also controls the expression of glutaredoxin GRX4, previously known to be involved in the regulation of Aft1 nuclear localization.
Consistently, we show that in the absence of Yap 5 Aft1 nuclear exclusion is slightly impaired. These studies provide further evidence that cells control iron homeostasis by using multiple pathways. In transmittance spectra, 4f-5d absorption line appeared at nm.
The corresponding amplification factor is 9. Full Text Available Neurofibromatosis type 2 NF2 is an autosomal dominant disorder characterized by the occurrence of schwannomas and meningiomas. Several studies have examined the ability of the NF2 gene product, merlin, to function as a tumor suppressor in diverse cell types; however, little is known about merlin growth regulation in meningiomas.
In Drosophila, merlin controls cell proliferation and apoptosis by signaling through the Hippo pathway to inhibit the function of the transcriptional coactivator Yorkie. The Hippo pathway is conserved in mammals. On the basis of these observations, we developed human meningioma cell lines matched for merlin expression to evaluate merlin growth regulation and investigate the relationship between NF2 status and Yes-associated protein YAP , the mammalian homolog of Yorkie.
NF2 loss in meningioma cells was associated with loss of contact-dependent growth inhibition, enhanced anchorage-independent growth and increased cell proliferation due to increased S-phase entry. In addition, merlin loss in both meningioma cell lines and primary tumors resulted in increased YAP expression and nuclear localization. Collectively, these results represent the first demonstration that merlin regulates cell growth in human cancer cells by suppressing YAP.
Genetic epistasis experiments provided evidence that this oncogenic pathway In addition, we have initiated high-throughput Although our studies have identified a critical role for nuclear Merlin in inhibition of. Pancreatic cancers driven by KRAS mutations require additional mutations for tumor progression. The tumor suppressor FBXW7 is altered in pancreatic cancers, but its contribution to pancreatic tumorigenesis is unknown.
Our data demonstrate that Fbxw7 is a potent suppressor of Kras G12D -induced pancreatic tumorigenesis due, at least in part, to negative regulation of Yap. Motta, A. The aim is to detect breast lesions, with dimensions of 5 mm in diameter, and with a specific activity ratio of between the cancer and breast tissue. A fast EM algorithm has been adapted to reconstruct all of the collected lines of flight, also at large incidence angles, by achieving 3D positioning capability of the lesion in the FOV.
The role of the breast compression has been studied. Two hot lesions in the active breast phantom are clearly visible in the reconstructed image.
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If you spot any typographical, grammatical or factual error in our site, then please let us know. Thanks in advance. Microsoft Office MS Office Microsoft Office questions with answer MS Office mcq : starting with microsoft office , photo editor was renamed to : is microsoft works is part of the microsoft office suite?
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