Transcription factor EB (TFEB) is a member of the MiTF/TFE (Microphthalmia/TFE) subfamily of basic/helix-loop-helix/leucine zipper transcription factors. This group of proteins is involved in the proliferation and development of specific cell types such as osteoclasts or melanocytes.
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As a prominent oncomir, miR-155 plays a role in many of the above oncogenic processes. It down-regulates BCL6 (B-cell lymphoma 6) protein [8], which is an evolutionarily conserved zinc finger transcription factor that contains an N-terminal POZ/BTB domain. As BCL6 has been shown to modulate the STAT-dependent Interleukin 4 (IL-4) responses of B cells, miR-155 acts to increase B cell functioning. Also, since BCL6 interacts with several co-repressor complexes to inhibit transcription, and its gene is frequently trans-located and hyper-mutated in diffuse large B cell lymphoma (DLBCL), miR-155 acts to enhance transcription and contribute to the pathogenesis of DLBCL. Reduction of BCL6 then leads to up-regulation of known BCL6 targets such as inhibitor of differentiation (Id2), Interleukin-6 (IL6), cMyc, Cyclin D1, and Mip1α/Ccl3, all of which promote cell survival and proliferation [8].. MiR-155 also upregulates Mxd1/Mad1, a network of basic helix-loop-helix leucine zipper transcription factors ...
The Myc/Max/Mad network comprises a group of transcription factors that co-interact to regulate gene-specific transcriptional activation or repression. This gene encodes a protein member of the Myc/Max/Mad network. This protein has a basic-Helix-Loop-Helix-zipper domain (bHLHzip) with which it binds the canonical DNA sequence CANNTG, known as the E box, following heterodimerization with Max proteins. This protein is a transcriptional repressor and an antagonist of Myc-dependent transcriptional activation and cell growth. This protein represses transcription by binding to DNA and recruiting Sin3 corepressor proteins through its N-terminal Sin3-interaction domain [1][4] ...
Whats a transcription factor of the basic helix-loop-helix leucine zipper family doing in the cytoplasm? Sans et al. explored why nearly all of the transcription factor MondoA and its binding partner protein called Mlx is found in the cytoplasm but the protein appears to function as a transcription factor in the nucleus. The authors found that in primary cultures of human muscle or erythroblast cells, MondoA and Mlx were associated with the mitochondria. Inhibition of nuclear shuttling of the proteins with an inhibitor of the CRM1 nuclear export factor caused MondoA (detected by confocal immunofluorescence microscopy) to accumulate in the nucleus. Thus, the authors suspected that MondoA could function to carry signals from the mitochondria to the nucleus. They obtained further circumstantial evidence for such a role from microarray experiments designed to detect genes transcribed in response to MondoA and Mlx. MondoA-Mlx regulated a broad range of targets, which included many genes associated ...
DALLAS - Oct. 18, 2004 - Researchers at UT Southwestern Medical Center at Dallas are one step closer to understanding how high carbohydrate diets lead to obesity and diabetes. Dr. Kosaku Uyeda, professor of biochemistry, has shown that a single protein called carbohydrate response element binding protein (ChREBP), discovered by his research group, activates several genes that cause cells in the liver to turn sugar into fat. Their work appears in two studies in Proceedings of the National Academy of Sciences. The first study, published in an earlier issue, is available online, and the second, also online, will appear in an upcoming issue of PNAS. Purifying ChREBP from rat livers took two postdoctoral fellows two years of very hard work, said Dr. Uyeda, senior author of both studies and a research scientist at the Veterans Affairs North Texas Health Care System. With the discovery of this factor, the biochemical mechanism of how carbohydrates are converted to fat has become clearer. Eating ...
Mondo Media is an American company that produces animation targeted at teens and young adults. The company was founded in 1988 in San Francisco, California. The company produces ad-supported, internet-based animated segments called Mondo Mini Shows. Mondos most successful shows are Happy Tree Friends, which was later adapted for TV, home video, a video game, and merchandise, Dick Figures which is adapted into a theatrical film, has a line of merchandises and was nominated for an Annie Award for Best Directing in an Animated Television or other Broadcast Venue Production, and Deep Space 69. Other series distributed by Mondo Media feature notable writers and voice actors. Short running series Off The Curb stars voice actors Carlos Alazraqui, Cedric Yarbrough, John Di Maggio, Fred Tatasciore, and Gary Anthony Williams. Mr. Wong was created and voiced by South Park writers Pam Brady and Kyle McCulloch. According to AdAge Magazine in January 2013, Mondo Media was the top-ranked and all-time most ...
human MONDOA protein: basic helix-loop-helix-leucine zipper transcriptional activator that constitutes a positive branch of a max-like network; RefSeq NM_014938
Myc-DDK-tagged ORF clone of Homo sapiens MAX-like protein X (MLX), transcript variant 1 as transfection-ready DNA - 10 µg - OriGene - cdna clones
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Sin3 forms the scaffold for a multiprotein corepressor complex that silences transcription via the action of histone deacetylases. Sin3 is recruited to the DNA by several DNA binding repressors, such as the helix-loop-helix proteins of the Mad family. Here, we elaborate on the Mad-Sin3 interaction based on a binding study, solution structure, and dynamics of the PAH2 domain of mSin3 in complex to an extended Sin3 interacting domain (SID) of 24 residues of Mad1. We show that SID residues Met7 and Glu23, outside the previously defined minimal binding motif, mediate additional hydrophobic and electrostatic interactions with PAH2. On the basis of these results we propose an extended consensus sequence describing the PAH2-SID interaction specifically for the Mad family, showing that residues outside the hydrophobic core of the SID interact with PAH2 and modulate binding affinity to appropriate levels ...
We proposed above that one way to generate MAX-like cells is to modify the energy model (Adelson and Bergen, 1985) by combining inputs from simple cells with a range of preferred spatial frequencies. To test the effect of this scenario on MAX-like behavior in complex cells, we created two versions of the energy model. In the classical version, the complex cells received input from a single pair of simple cells with identical preferred spatial frequencies and receptive fields 90° out of spatial phase from one another. The sensitivity of each simple cell varied (in the direction perpendicular to the preferred orientation) as a Gabor function of distance: S1 = cos(1.5πx) × e−x2/0.23; S2 = sin(1.5πx) × e−x2/0.23.. In the MAX-like version of the model, the complex cell received input from an additional pair of simple cells with a preferred spatial frequency of a little less than half that of those in pair 1: S3 = cos(0.6πx) × e−x2/0.23; S4 = sin(0.6πx) × e−x2/0.23.. For each version ...
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In recent years, sugars have been recognized as important signal molecules that affect a variety of physiological responses and in particular regulate genes involved in photosynthesis, sink metabolism, and defense response (Koch, 1996;Smeekens, 1998; Roitsch, 1999; Sheen et al., 1999). Whereas the effect of sugars on gene regulation is well established, the nature of the sugar signal, and the molecular mechanisms involved in sugar perception and intracellular signal transmission, are largely unknown. Suc is the major form of translocated carbon in higher plants and was shown to regulate a number of carbohydrate-responsive genes. Whereas in many cases the effects of Suc could be mimicked by hexoses, such as Glc and Fru, a few studies demonstrated the existence of Suc-specific regulatory pathways (Chiou and Bush, 1998; Rook et al., 1998). In principle, a sugar signal could be generated by extracellular recognition via a soluble or membrane-bound receptor molecule or by intracellular sensing at ...
This prezi provides students with information about the library and resources available to them to use throughout the school year.
Psychiatrists measuring the degree of similarity between dreams and psychotic ruminations report some strange features common to both.
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Plasmid pFETCh_MLX from Dr. Eric Mendenhalls lab contains the insert MLX homology arms and is published in Genome Res. 2015 Sep 9. This plasmid is available through Addgene.
GLHA2_ONCKE (P69063 ), GLHA2_ONCTS (P69062 ), GLHA_ACALA (P30970 ), GLHA_AILFU (Q8HZS0 ), GLHA_AILME (Q8WN20 ), GLHA_ANGAN (P27794 ), GLHA_AOTNA (Q3HRV5 ), GLHA_BALAC (P37036 ), GLHA_BOSMU (Q19PY8 ), GLHA_BOVIN (P01217 ), GLHA_BUBBU (Q9GL36 ), GLHA_CALJA (P51499 ), GLHA_CANLF (Q9XSW8 ), GLHA_CAPHI (Q8WMW8 ), GLHA_CAVPO (Q9JK68 ), GLHA_CERNI (Q8WMR3 ), GLHA_CLAGA (P53542 ), GLHA_COTJA (P68242 ), GLHA_CTEID (P30983 ), GLHA_EQUAS (Q28365 ), GLHA_EQUBU (O46642 ), GLHA_FELCA (Q52R91 ), GLHA_FUNHE (P47744 ), GLHA_HORSE (P01220 ), GLHA_HUMAN (P01215 ), GLHA_HYPMO (P37037 ), GLHA_ICTPU (Q9YGP3 ), GLHA_LITCT (P80051 ), GLHA_MACFA (Q9BEH3 ), GLHA_MACMU (P22762 ), GLHA_MACRU (P68267 ), GLHA_MASCO (Q9ERG4 ), GLHA_MELGA (P68241 ), GLHA_MERUN (Q9ERJ6 ), GLHA_MESAU (Q9ERG5 ), GLHA_MICMO (Q9ERG3 ), GLHA_MONDO (Q6YNX4 ), GLHA_MORSA (Q91119 ), GLHA_MOUSE (P01216 ), GLHA_MURCI (P12836 ), GLHA_NIPNI (Q8JIE9 ), GLHA_PANTA (Q9BDI8 ), GLHA_PHYCD (P25329 ), GLHA_PIG (P01219 ), GLHA_RABIT (P07474 ), GLHA_RAT (P11962 ), ...
To all the cunts who recently purchased those Mondo reissues and immediately flipped them on E-Bay for $140: I wish you all had one neck and I had my hands around it. Of course this frustrating tendency is endemic to the same miserable fucks who watched their SunnO))) stock plummet and before that their Japanese hardcore punk. I could go on and on about how easy it was to pluck great soundtracks (and lots of not-so-great soundtracks) out of the $1 bins back in the not-so-distant day but that would only raise my blood pressure and as a sympathetic friend reminded me the other day, its just not worth the effort. After all, the current soundtrack craze will soon join the hula hoop, the mickey mouse hat, the Beta video, the Myspace bulletin and the porno grind sample on that inevitable death march toward total obsolescence. Furthermore, there are occasionally unexpected surprises that come with such reappraisals that bring great joy to real fans. Thanks to the tireless efforts of laudable ...
Hi, purchased one of each, in exactly the same size (28.0 Mondo). Dane has done an article (http://coldthistle.blogspot.com/2013/12/reality-check-dynafit-tlt6-and-la.html) with his usual attention to detail but he fit in two different shell sizes. Here is a direct comparison of weights. Weights (as shown in pics) was done on a food scale. I tared it about 8 times first to make sure it returned to zero correctly after each boot. the TLT6 and Spectre are both brand new out of box, have all
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Background: ChREBP (carbohydrate response element binding protein) is a glucose-responsive transcription factor that is known to be an important regulator of glycolytic and lipogenic genes in response to glucose. We hypothesized that activation of ChREBP could be relevant to anoxia survival by the anoxia-tolerant turtle, Trachemys scripta elegans. Methods: Expression of ChREBP in response to 5 and 20 h of anoxia was examined using RT-PCR and Western immunoblotting. In addition, subcellular localization and DNA-binding activity of ChREBP protein were assessed and transcript levels of liver pyruvate kinase (LPK), a downstream gene under ChREBP control were quantified using RT-PCR. Results: ChREBP was anoxia-responsive in kidney and liver, with transcript levels increasing by 1.2-1.8 fold in response to anoxia and protein levels increasing by 1.8-1.9 fold. Enhanced nuclear presence under anoxia was also observed in both tissues by 22-2.8 fold. A 4.2 fold increase in DNA binding activity of ChREBP was also
TY - JOUR. T1 - Brain metastasis of crystal-deficient, CD68-positive alveolar soft part sarcoma. T2 - Ultrastructural features and differential diagnosis. AU - Cykowski, Matthew D.. AU - Hicks, John. AU - Sandberg, David I.. AU - Olar, Adriana. AU - Bridge, Julia A.. AU - Greipp, Patricia T.. AU - Navarro, Patricia. AU - Kolodziej, Steven. AU - Bhattacharjee, Meenakshi B.. PY - 2015/2/1. Y1 - 2015/2/1. N2 - We report a case of alveolar soft part sarcoma (ASPS) presenting as an isolated frontal lobe metastasis. The tumor demonstrated little or no immunoreactivity for a broad panel of antibodies yet strong, diffuse immunoreactivity with CD68. On electron microscopy, the characteristic rectangular to rhomboid crystalline inclusions of ASPS were not present. Electron-dense granules resembling peroxisomes were present, sometimes in association with elongated granular structures having a periodic, lattice-like arrangement. Metastatic ASPS was confirmed by demonstration of an ASPSCR1-TFE3 fusion and ...
Find people with Alveolar Soft Part Sarcoma through the map. Connect with them and share experiences. Join the Alveolar Soft Part Sarcoma community.
Among the landmarks for apicobasal cell polarity, microvilli are actin-based protrusions on the apical surfaces of epithelial and sensory cells. In epithelia of the small intestine and kidney proximal tubule, closely packed microvilli known as the brush border are observed on their apical plasma membranes. They participate in a variety of functions such as nutrient absorption, mechanosensory transduction, and phototransduction. The core structure of microvilli is comprised of parallel actin filaments, and numerous actin-binding proteins, including villin, espin, fimbrin, fascin, and myosins as well as ezrin/ radixin/moesin (ERM) proteins, have been identified as components of microvilli (for reviews see DeRosier and Tilney 2000; Bretscher et al., 2002; Frolenkov et al., 2004). Some transmembrane proteins such as Cad99C, the Drosophila melanogaster orthologue of the vertebrate procadherin 15 (DAlterio et al., 2005; Schlichting et al., 2006), are also known to be constituents of ...
Chinese version below) Man Yi Mandy YAU, 21 years old, is a junior student majoring in Cultural Studies at The Chinese University of Hong Kong. She is currently suffering from the Alveolar Soft Part Sarcoma (ASPS). It first occurred in her right thigh in 2011, soon it spread to her lungs, and now it appears in her right brain. It is a very rare form of cancer. According to the Hong Kong Cancer Registry (HKCaR), there are only 191 new cases every year in average. The incident rate is 2 per 100,000 persons overall. Man Yi is tough, brave, and optimistic. The third time to encounter the cancer, she understands that she has limited time so she starts writing about her life and thoughts publicly on Facebook. Man Yi describes the recent episode of her life as "the best days and the worst days". To be honest, she has already planned for the worst. However, at the same time, because of ASPS, she is receiving many blessings and love from friends, teachers, and even strangers. She is writing her "last ...
Alveolar soft part sarcoma (ASPS) has often proven to be resistant to conventional doxorubicin-based chemotherapy, but tyrosine kinase inhibitors (TKIs) and imm
Provides information to potential participants on the following clinical trial: Phase II Study of Cediranib (AZD2171) in Patients With Alveolar Soft Part Sarcoma
Lysosomes degrade and recycle transported cellular components and internalized material by fusing with autophagosomes, phagosomes, and late endosomes. The resulting lysosomal breakdown products are used to generate new macromolecules and to provide energy in response to the nutritional needs of the cell. Recently, lysosome functions were expanded to include roles in nutrient sensing and energy metabolism (4). In this study, we report that the exposure of macrophages to LPS or heat-killed bacteria raises AGS3 levels. The increases in AGS3 reduced signaling through the mTOR pathway. However, in a nutrient-replete state this did not lead to a substantive increase in autophagy, but it did facilitate the nuclear translocation of TFEB, which transcriptionally activates many of the genes involved in lysosomal biogenesis and function. The subsequent increase in lysosomal biogenesis/function helped macrophages to resist intracellular infections by several strains of antibiotic-resistant ...
The role of peroxisome proliferator-activated receptor α (PPAR-α) in innate host defense is largely unknown. In this study, we show that PPAR-α is essential for antimycobacterial responses via activation of transcription factor EB (TFEB) transcription and inhibition of lipid body formation. PPAR-α deficiency resulted in an increased bacterial load and exaggerated inflammatory responses during mycobacterial infection. PPAR-α agonists promoted autophagy, lysosomal biogenesis, phagosomal maturation, and antimicrobial defense against Mycobacterium tuberculosis or M. bovis bacillus Calmette-Guérin. PPAR-α agonists regulated multiple genes involved in autophagy and lysosomal biogenesis, including Lamp2, Rab7, and Tfeb in bone marrow-derived macrophages. Silencing of TFEB reduced phagosomal maturation and antimicrobial responses, but increased macrophage inflammatory responses during mycobacterial infection. Moreover, PPAR-α activation promoted lipid catabolism and fatty acid β-oxidation in ...
The microphthalmia family of transcription factors (MiT/TFEs) controls lysosomal biogenesis and is negatively regulated by the nutrient sensor mTORC1. However, the mechanisms by which cells with constitutive mTORC1 signaling maintain lysosomal catabolism remain to be elucidated. Using the murine epidermis as a model system, we found that epidermal Tsc1 deletion resulted in a phenotype characterized by wavy hair and curly whiskers, and was associated with increased EGFR and HER2 degradation. Unexpectedly, constitutive mTORC1 activation with Tsc1 loss increased lysosomal content via upregulated expression and activity of MiT/TFEs, whereas genetic deletion of Rheb or Rptor or prolonged pharmacologic mTORC1 inactivation had the reverse effect. This paradoxical increase in lysosomal biogenesis by mTORC1 was mediated by feedback inhibition of AKT, and a resulting suppression of AKT-induced MiT/TFE downregulation. Thus, inhibiting hyperactive AKT signaling in the context of mTORC1 loss-of-function ...
TFEB is a master gene for lysosomal biogenesis.[7] It encodes a transcription factor that coordinates expression of lysosomal hydrolases, membrane proteins and genes involved in autophagy.[7][8] Upon nutrient depletion and under aberrant lysosomal storage conditions such as in lysosomal storage diseases, TFEB translocates from the cytoplasm to the nucleus, resulting in the activation of its target genes.[7][8] TFEB overexpression in cultured cells induces lysosomal biogenesis, exocytosis and autophagy. [7][8][9] Viral-mediated TFEB overexpression in cellular and mouse models of lysosomal storage disorders and in common neurodegenerative diseases such as Huntington, Parkinson and Alzheimer diseases, resulted in intracellular clearance of accumulating molecules and rescue of disease phenotypes.[7][9][10][11][12] TFEB is activated by PGC1-alpha and promotes reduction of htt aggregation and neurotoxicity in a mouse model of Huntington disease.[13] TFEB overexpression has been found in patients with ...
Ultimate Experience: mondo Solitaire is the ultimate Solitaire experience for your iPhone or iPod touch. With over 100 games and over 200 different combinations of gameplay, youre sure to find your favorites, such as Klondike and FreeCell, plus many new games to discover, like Angkor Wat and Xerces.. The look of pure Win mondo Solitaires beautiful, crisp graphics let you easily identify your cards and assess your current move. Clever tools like the magnifying glass and the paper clip help you intuitively manage your game. Find your Game: A familiar library search lets you sort and select all of your games -- by name, style, favorites, and even popularity. The categorized interface makes it really easy to find the exact game you want to play. Casual Gameplay: mondo Solitaire is a true casual game you can play whenever and wherever, yet dismiss quickly to take phone calls or send messages. When finished, simply tap on the game applications icon and head right back into the action!. ...
Sure we love the Mac OSX, but hasnt it always felt like it was missing just a little something? After much deliberation, our staff deduced that void was surely a fun and incredible-to-look-at Solitaire game! Here at Ambrosia, our developers have really outdone themselves in creating Mondo Solitaire for Mac, providing a scintillating solution for your gaming needs. With over 300 games, vivid graphics, and a smooth, intuitive interface, Mondo is not just another solitaire game-- it is THE Solitaire game for the Mac!. To keep the smiles going, we are happy to celebrate the release of Faces by our good friends at Tap Tap Tap. Faces is a fun app that lets you transform plain photos of your friends into hilarious portraits using your choice of around 200 zany props! The best part is that you dont even need to purchase to get Mondo for Mac-- simply visit the site to learn more!. ...
Cellular clearance is a fundamental process required by the cells of every species. In eukaryotes, most of the cellular clearing processes occur in a specialized organelle, the lysosome. Given that the requirements of the degradative machinery in a cell may vary depending on tissue type, age and environmental conditions, we postulated that a system coordinates lysosomal activity and that lysosomal function is subject to transcriptional regulation. Using a systems biology-based approach, we discovered a gene regulatory network (CLEAR: Coordinated Lysosomal Enhancement And Regulation) that controls lysosomal biogenesis and function (Sardiello et al, Science 2009) and a master gene, the bHLH-leucine zipper transcription factor TFEB, which binds to CLEAR target sites in the promoter of lysosomal genes and positively regulates their expression (Sardiello et al, Science 2009). TFEB overexpression induces lysosomal biogenesis and increases the cells ability to degrade complex molecules such as mutated ...
Cellular organelles allow the localized regulation of specialized processes. Under certain conditions, such as increased growth, organelles may be required to alter their function. Coordinated regulation of the gene networks required for mitochondrial and endoplasmic reticulum function has been observed. Now, Sardiello et al. (p. 473; published online 25 June) have discovered a gene network regulating the lysosome, the major organelle involved in the degradation of internalized macromolecules. Many lysosomal genes were regulated by a single transcription factor, TFEB. TFEB itself can be activated when the lysosome malfunctions and can regulate both the abundance of lysosomes found in the cell, as well as the ability to degrade complex molecules, including a mutant protein that accumulates in patients with Huntingtons disease. These results may have implications for the treatment of human lysosomal storage disorders, which are characterized by the aberrant accumulation of macromolecules causing ...
The exact mechanism by which the atherogenic lipids oxLDL and CC perturb lysosomal function is not known. Oxidized LDL is taken up by macrophage scavenger receptors and is trafficked to the endolysosomal compartment. Oxidized LDL can then bind and inactivate cathepsins with high affinity,30 inactivate other proteases including the Naβ Gases,31 and produce a form of apolipoproteinB that is highly resistant to hydrolysis.32,33 OxLDL has also been demonstrated in endothelial and smooth muscle cells to inhibit activity and expression of the enzyme crucial to cholesterol ester hydrolysis, LIPA.34 Most recently, the formation of cholesterol microcrystals and ensuing disruption of lysosomal integrity has directly been linked to the buildup of oxLDL in the lysosomal compartment.14 Such a mechanism would favor the notion that the mechanism of lysosomal dysfunction mediated by oxLDL and larger CC lies in a continuum (with the oxLDL pool eventually precipitating as insoluble crystals). Our data support ...