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Academic literature on the topic 'MCTz'

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Published: 9 March 2023
Last updated: 10 March 2023

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Journal articles on the topic "MCTz"

1

Bonen, Arend, Miriam Heynen, and Hideo Hatta. "Distribution of monocarboxylate transporters MCT1-MCT8 in rat tissues and human skeletal muscle." Applied Physiology, Nutrition, and Metabolism 31, no. 1 (February 1, 2006): 31–39. http://dx.doi.org/10.1139/h05-002.

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In the past decade, a family of monocarboxylate transporters (MCTs) have been identified that can potentially transport lactate, pyruvate, ketone bodies, and branched-chain ketoacids. Currently, 14 such MCTs are known. However, many orphan transporters exist that have transport capacities that remain to be determined. In addition, the tissue distribution of many of these MCTs is not well defined. Such a cataloging can, at times, begin to suggest the metabolic role of a particular MCT. Recently, a number of antibodies against selected MCTs (MCT1, -2, -4, and -5 to -8) have become commercially available. Therefore, we examined the protein expression of these MCTs in a large number of rat tissues (heart, skeletal muscle, skin, brain, testes, vas deferens, adipose tissue, liver, kidney, spleen, and pancreas), as well as in human skeletal muscle. Unexpectedly, many tissues coexpressed 4-5 MCTs. In particular, in rat skeletal muscle MCT1, MCT2, MCT4, MCT5, and MCT6 were observed. In human muscle, these same MCTs were present. We also observed a pronounced MCT7 signal in human muscle, whereas a very faint signal occurred for MCT8. In rat heart, which is an important metabolic sink for lactate, we confirmed that MCT1 and -2 were expressed. In addition, MCT6 and -8 were also prominently expressed in this tissue, although it is known that MCT8 does not transport aromatic amino acids or lactate. This catalog of MCTs in skeletal muscle and other tissues has revealed an unexpected complexity of coexpression, which makes it difficult to associate changes in monocarboxylate transport with the expression of a particular MCT. The differences in transport kinetics for lactate and pyruvate are only known for MCT1, -2 and -4. Transport kinetics remain to be established for many other MCTs. In conclusion, this study suggests that in skeletal muscle, as well as other tissues, lactate and pyruvate transport rates may not only involve MCT1 and -4, as other monocarboxylate transporters are also expressed in rat (MCT2, -5, -6) and human skeletal muscle (MCT2, -5, -6, -7).Key words: muscle, lactate, pyruvate, human, rat.
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2

PRICE, T. Nigel, N. Vicky JACKSON, and P. Andrew HALESTRAP. "Cloning and sequencing of four new mammalian monocarboxylate transporter (MCT) homologues confirms the existence of a transporter family with an ancient past." Biochemical Journal 329, no. 2 (January 15, 1998): 321–28. http://dx.doi.org/10.1042/bj3290321.

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Measurement of monocarboxylate transport kinetics in a range of cell types has provided strong circumstantial evidence for a family of monocarboxylate transporters (MCTs). Two mammalian MCT isoforms (MCT1 and MCT2) and a chicken isoform (REMP or MCT3) have already been cloned, sequenced and expressed, and another MCT-like sequence (XPCT) has been identified. Here we report the identification of new human MCT homologues in the database of expression sequence tags and the cloning and sequencing of four new full-length MCT-like sequences from human cDNA libraries, which we have denoted MCT3, MCT4, MCT5 and MCT6. Northern blotting revealed a unique tissue distribution for the expression of mRNA for each of the seven putative MCT isoforms (MCT1-MCT6 and XPCT). All sequences were predicted to have 12 transmembrane (TM) helical domains with a large intracellular loop between TM6 and TM7. Multiple sequence alignments showed identities ranging from 20% to 55%, with the greatest conservation in the predicted TM regions and more variation in the C-terminal than the N-terminal region. Searching of additional sequence databases identified candidate MCT homologues from the yeast Saccharomyces cerevisiae, the nematode worm Caenorhabditis elegans and the archaebacterium Sulfolobus solfataricus. Together these sequences constitute a new family of transporters with some strongly conserved sequence motifs, the possible functions of which are discussed.
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3

Becker, Helen M., Nilufar Mohebbi, Angelica Perna, Vadivel Ganapathy, Giovambattista Capasso, and Carsten A. Wagner. "Localization of members of MCT monocarboxylate transporter family Slc16 in the kidney and regulation during metabolic acidosis." American Journal of Physiology-Renal Physiology 299, no. 1 (July 2010): F141—F154. http://dx.doi.org/10.1152/ajprenal.00488.2009.

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The monocarboxylate transporter family (MCT) comprises 14 members with distinct transport properties and tissue distribution. The kidney expresses several members of the MCT family, but only little is known about their exact distribution and function. Here, we investigated selected members of the MCT family in the mouse kidney. MCT1, MCT2, MCT7, and MCT8 localized to basolateral membranes of the epithelial cells lining the nephron. MCT1 and MCT8 were detected in proximal tubule cells whereas MCT7 and MCT2 were located in the thick ascending limb and the distal tubule. CD147, a β-subunit of MCT1 and MCT4, showed partially overlapping expression with MCT1 and MCT2. However, CD147 was also found in intercalated cells. We also detected SMCT1 and SMCT2, two Na+-dependent monocarboxylate cotransporters, on the luminal membrane of type A intercalated cells. Moreover, mice were given an acid load for 2 and 7 days. Acidotic animals showed a marked but transient increase in urinary lactate excretion. During acidosis, a downregulation of MCT1, MCT8, and SMCT2 was observed at the mRNA level, whereas MCT7 and SMCT1 showed increased mRNA abundance. Only MCT7 showed lower protein abundance whereas all other transporters remained unchanged. In summary, we describe for the first time the localization of various MCT transporters in mammalian kidney and demonstrate that metabolic acidosis induces a transient increase in urinary lactate excretion paralleled by lower MCT7 protein expression.
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4

Chidlow, Glyn, John P. M. Wood, Mark Graham, and Neville N. Osborne. "Expression of monocarboxylate transporters in rat ocular tissues." American Journal of Physiology-Cell Physiology 288, no. 2 (February 2005): C416—C428. http://dx.doi.org/10.1152/ajpcell.00037.2004.

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The aim of the present study was to determine the distribution of monocarboxylate transporter (MCT) subtypes 1-4 in the various structures of the rat eye by using a combination of conventional and real-time RT-PCR, immunoblotting, and immunohistochemistry. Retinal samples expressed mRNAs encoding all four MCTs. MCT1 immunoreactivity was observed in photoreceptor inner segments, Müller cells, retinal capillaries, and the two plexiform layers. MCT2 labeling was concentrated in the inner and outer plexiform layers. MCT4 immunolabeling was present only in the inner retina, particularly in putative Müller cells, and the plexiform layers. No MCT3 labeling could be observed. The retinal pigment epithelium (RPE)/choroid expressed high levels of MCT1 and MCT3 mRNAs but lower levels of MCT2 and MCT4 mRNAs. MCT1 was localized to the apical and MCT3 to the basal membrane of the RPE, whereas MCT2 staining was faint. Although MCT1-MCT4 mRNAs were all detectable in iris and ciliary body samples, only MCT1 and MCT2 proteins were expressed. These were present in the iris epithelium and the nonpigmented epithelium of the ciliary processes. MCT4 was localized to the smooth muscle lining of large vessels in the iris-ciliary body and choroid. In the cornea, MCT1 and MCT2 mRNAs and proteins were detectable in the epithelium and endothelium, whereas evidence was found for the presence of MCT4 and, to a lesser extent, MCT1 in the lens epithelium. The unique distribution of MCT subtypes in the eye is indicative of the pivotal role that these transporters play in the maintenance of ocular function.
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Pinheiro, Céline, Rui M. Reis, Sara Ricardo, Adhemar Longatto-Filho, Fernando Schmitt, and Fátima Baltazar. "Expression of Monocarboxylate Transporters 1, 2, and 4 in Human Tumours and Their Association with CD147 and CD44." Journal of Biomedicine and Biotechnology 2010 (2010): 1–7. http://dx.doi.org/10.1155/2010/427694.

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Monocarboxylate transporters (MCTs) are important cellular pH regulators in cancer cells; however, the value of MCT expression in cancer is still poorly understood. In the present study, we analysed MCT1, MCT2, and MCT4 protein expression in breast, colon, lung, and ovary neoplasms, as well as CD147 and CD44. MCT expression frequency was high and heterogeneous among the different tumours. Comparing with normal tissues, there was an increase in MCT1 and MCT4 expressions in breast carcinoma and a decrease in MCT4 plasma membrane expression in lung cancer. There were associations between CD147 and MCT1 expressions in ovarian cancer as well as between CD147 and MCT4 in both breast and lung cancers. CD44 was only associated with MCT1 plasma membrane expression in lung cancer. An important number of MCT1 positive cases are negative for both chaperones, suggesting that MCT plasma membrane expression in tumours may depend on a yet nonidentified regulatory protein.
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6

HALESTRAP, Andrew P., and Nigel T. PRICE. "The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation." Biochemical Journal 343, no. 2 (October 8, 1999): 281–99. http://dx.doi.org/10.1042/bj3430281.

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Monocarboxylates such as lactate and pyruvate play a central role in cellular metabolism and metabolic communication between tissues. Essential to these roles is their rapid transport across the plasma membrane, which is catalysed by a recently identified family of proton-linked monocarboxylate transporters(MCTs). Nine MCT-related sequences have so far been identified in mammals, each having a different tissue distribution, whereas six related proteins can be recognized in Caenorhabditis elegansand 4 in Saccharomyces cerevisiae. Direct demonstration of proton-linked lactate and pyruvate transport has been demonstrated for mammalian MCT1-MCT4, but only for MCT1 and MCT2 have detailed analyses of substrate and inhibitor kinetics been described following heterologous expression in Xenopusoocytes. MCT1 is ubiquitously expressed, but is especially prominent in heart and red muscle, where it is up-regulated in response to increased work, suggesting a special role in lactic acid oxidation. By contrast, MCT4 is most evident in white muscle and other cells with a high glycolytic rate, such as tumour cells and white blood cells, suggesting it is expressed where lactic acid efflux predominates. MCT2 has a ten-fold higher affinity for substrates than MCT1 and MCT4 and is found in cells where rapid uptake at low substrate concentrations may be required, including the proximal kidney tubules, neurons and sperm tails. MCT3 is uniquely expressed in the retinal pigment epithelium. The mechanisms involved in regulating the expression of different MCT isoforms remain to be established. However, there is evidence for alternative splicing of the 5′- and 3′-untranslated regions and the use of alternative promoters for some isoforms. In addition, MCT1 and MCT4 have been shown to interact specifically with OX-47 (CD147), a member of the immunoglobulin superfamily with a single transmembrane helix. This interaction appears to assist MCT expression at the cell surface. There is still much work to be done to characterize the properties of the different isoforms and their regulation, which may have wide-ranging implications for health and disease. In the future it will be interesting to explore the linkage of genetic diseases to particular MCTs through their chromosomal location.
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7

Ovens, Matthew J., Christine Manoharan, Marieangela C. Wilson, Clarey M. Murray, and Andrew P. Halestrap. "The inhibition of monocarboxylate transporter 2 (MCT2) by AR-C155858 is modulated by the associated ancillary protein." Biochemical Journal 431, no. 2 (September 28, 2010): 217–25. http://dx.doi.org/10.1042/bj20100890.

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In mammalian cells, MCTs (monocarboxylate transporters) require association with an ancillary protein to enable plasma membrane expression of the active transporter. Basigin is the preferred binding partner for MCT1, MCT3 and MCT4, and embigin for MCT2. In rat and rabbit erythrocytes, MCT1 is associated with embigin and basigin respectively, but its sensitivity to inhibition by AR-C155858 was found to be identical. Using RT (reverse transcription)–PCR, we have shown that Xenopus laevis oocytes contain endogenous basigin, but not embigin. Co-expression of exogenous embigin was without effect on either the expression of MCT1 or its inhibition by AR-C155858. In contrast, expression of active MCT2 at the plasma membrane of oocytes was significantly enhanced by co-expression of exogenous embigin. This additional transport activity was insensitive to inhibition by AR-C155858 unlike that by MCT2 expressed with endogenous basigin that was potently inhibited by AR-C155858. Chimaeras and C-terminal truncations of MCT1 and MCT2 were also expressed in oocytes in the presence and absence of exogenous embigin. L-Lactate Km values for these constructs were determined and revealed that the TM (transmembrane) domains of an MCT, most probably TM7–TM12, but not the C-terminus, are the major determinants of L-lactate affinity, whereas the associated ancillary protein has little or no effect. Inhibitor titrations of lactate transport by these constructs indicated that embigin modulates MCT2 sensitivity to AR-C155858 through interactions with both the intracellular C-terminus and TMs 3 and 6 of MCT2. The C-terminus of MCT2 was found to be essential for its expression with endogenous basigin.
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8

Shrestha, Pawan, Amy E. Whelchel, Sarah E. Nicholas, Wentao Liang, Jian-Xing Ma, and Dimitrios Karamichos. "Monocarboxylate Transporters: Role and Regulation in Corneal Diabetes." Analytical Cellular Pathology 2022 (October 26, 2022): 1–10. http://dx.doi.org/10.1155/2022/6718566.

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Diabetes mellitus (DM) is a group of metabolic diseases that is known to cause structural and functional ocular complications. In the human cornea, DM-related complications affect the epithelium, stroma, and nerves. Monocarboxylate transporters (MCTs) are a family of proton-linked plasma membrane transporters that carry monocarboxylates across plasma membranes. In the context of corneal health and disease, their role, presence, and function are largely undetermined and solely focused on the most common MCT isoforms, 1 through 4. In this study, we investigated the regulation of MCT1, 2, 4, 5, 8, and 10, in corneal DM, using established 3D self-assembled extracellular matrix (ECM) in vitro models. Primary stromal corneal fibroblasts were isolated from healthy (HCFs), type I (T1DMs), and type II (T2DMs) DM donors. Monoculture 3D constructs were created by stimulating stromal cells on transwells with stable vitamin C for two or four weeks. Coculture 3D constructs were created by adding SH-SY5Y neurons at two different densities, 12 k and 500 k, on top of the monocultures. Our data showed significant upregulation of MCT1 at 4 weeks for HCF, T1DM, and T2DM monocultures, as well as the 500 k nerve cocultures. MCT8 was significantly upregulated in HCF and T1DM monocultures and all of the 500 k nerve cocultures. Further, MCT10 was only expressed at 4 weeks for all cocultures and was limited to HCFs and T1DMs in monocultures. Immunofluorescence analysis showed cytoplasmic MCT expression for all cell types and significant downregulation of both MCT2 and MCT4 in HCFs, when compared to T1DMs and T2DMs. Herein, we reveal the existence and modulation of MCTs in the human diabetic cornea in vitro. Changes appeared dependent on neuronal density, suggesting that MCTs are very likely critical to the neuronal defects observed in diabetic keratopathy/neuropathy. Further studies are warranted in order to fully delineate the role of MCTs in corneal diabetes.
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9

Takimoto, Masaki, and Taku Hamada. "Acute exercise increases brain region-specific expression of MCT1, MCT2, MCT4, GLUT1, and COX IV proteins." Journal of Applied Physiology 116, no. 9 (May 1, 2014): 1238–50. http://dx.doi.org/10.1152/japplphysiol.01288.2013.

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The brain is capable of oxidizing lactate and ketone bodies through monocarboxylate transporters (MCTs). We examined the protein expression of MCT1, MCT2, MCT4, glucose transporter 1 (GLUT1), and cytochrome- c oxidase subunit IV (COX IV) in the rat brain within 24 h after a single exercise session. Brain samples were obtained from sedentary controls and treadmill-exercised rats (20 m/min, 8% grade). Acute exercise resulted in an increase in lactate in the cortex, hippocampus, and hypothalamus, but not the brainstem, and an increase in β-hydroxybutyrate in the cortex alone. After a 2-h exercise session MCT1 increased in the cortex and hippocampus 5 h postexercise, and the effect lasted in the cortex for 24 h postexercise. MCT2 increased in the cortex and hypothalamus 5–24 h postexercise, whereas MCT2 increased in the hippocampus immediately after exercise, and remained elevated for 10 h postexercise. Regional upregulation of MCT2 after exercise was associated with increases in brain-derived neurotrophic factor and tyrosine-related kinase B proteins, but not insulin-like growth factor 1. MCT4 increased 5–10 h postexercise only in the hypothalamus, and was associated with increased hypoxia-inducible factor-1α expression. However, none of the MCT isoforms in the brainstem was affected by exercise. Whereas GLUT 1 in the cortex increased only at 18 h postexercise, COX IV in the hippocampus increased 10 h after exercise and remained elevated for 24 h postexercise. These results suggest that acute prolonged exercise induces the brain region-specific upregulation of MCT1, MCT2, MCT4, GLUT1, and COX IV proteins.
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Hadjiagapiou, Christos, Larry Schmidt, Pradeep K. Dudeja, Thomas J. Layden, and Krishnamurthy Ramaswamy. "Mechanism(s) of butyrate transport in Caco-2 cells: role of monocarboxylate transporter 1." American Journal of Physiology-Gastrointestinal and Liver Physiology 279, no. 4 (October 1, 2000): G775—G780. http://dx.doi.org/10.1152/ajpgi.2000.279.4.g775.

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The short-chain fatty acid butyrate was readily taken up by Caco-2 cells. Transport exhibited saturation kinetics, was enhanced by low extracellular pH, and was Na+independent. Butyrate uptake was unaffected by DIDS; however, α-cyano-4-hydroxycinnamate and the butyrate analogs propionate and l-lactate significantly inhibited uptake. These results suggest that butyrate transport by Caco-2 cells is mediated by a transporter belonging to the monocarboxylate transporter family. We identified five isoforms of this transporter, MCT1, MCT3, MCT4, MCT5, and MCT6, in Caco-2 cells by PCR, and MCT1 was found to be the most abundant isoform by RNase protection assay. Transient transfection of MCT1, in the antisense orientation, resulted in significant inhibition of butyrate uptake. The cells fully recovered from this inhibition by 5 days after transfection. In conclusion, our data showed that the MCT1 transporter may play a major role in the transport of butyrate into Caco-2 cells.
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Dissertations / Theses on the topic "MCTz"

1

Ovens, Matthew James. "Further characterisation of substrate, inhibitor and ancillary protein specificity of MCT1, MCT2, MCT4 and MCT6." Thesis, University of Bristol, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.528104.

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The MonoCarboxylate Transporter (MCT) family of transmembrane proteins contain 14 members of which 6 have been functionally characterized. Of these characterised MCTs only MCTs 1-4 have been shown to transport lactate. These MCTs also facilitate the movement of pyruvate and ketone bodies across the plasma membrane (PM) in cotransport with a proton. For trafficking to and function at the PM MCTl, MCT3 and MCT4 require association with the monotopic ancillary glycoprotein basigin whereas MCT2 prefers association with embigin. This thesis has investigated the sensitivity of MCTl, MCT2 and MCT4 to the highly potent and selective MCTI inhibitor, ARC155858, discovered by AstraZeneca. Chimeras of MCTI and MCT4 were constructed and expressed in Xenopus laevis oocytes for transport studies to determine their inhibitor sensitivity. These identified a region between transmembrane domains (TMs) 7 and 10 of MCTI with which AR-C155858 binds from the cytoplasmic side. ARC155858 was shown to inhibit MCT2 but sensitivity was found to be dependent on the ancillary protein with which it is associated. Co-expression with embigin decreased the sensitivity of MCT2, but not MCTl, to AR-CI55858. The MCT C-terminus was shown to playa role in the interaction between MCT and ancillary protein which is secondary to interactions between the TM of the ancillary protein and TMs3 and 6 of the MCT. Additional studies were performed to characterise the substrate specificity of the orphan transporter, MCT6. Initial work suggested that products of pyruvate decarboxylation or polymerisation will provide lead compounds in the continuing search for the physiological substrate of MCT6, with formate another potential substrate. During this work it was also discovered that MCTI can catalyse the transport of specific dicarboxylates at low pH.
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2

MONTEMAGNI, CHIARA. "Geochronology and kinematics of crustal scale shear zones in the Himalayan collisional belt." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2020. http://hdl.handle.net/10281/269277.

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L’Himalaya è classicamente considerata una catena orogenica strutturalmente cilindrica per l’impressionante continuità laterale, da ovest ad est, delle principali unità lito-tettoniche e zone di taglio, caratteristica peculiare di questa catena collisionale. L’esumazione del cuore metamorfico della catena, il Greater Himalayan Sequence (GHS), è favorita dall’attività di due zone di taglio regionali a cinematica opposta: la Main Central Thrust zone (MCTz) a cinematica compressiva e il South Tibetan Detachment System (STDS) a cinematica normale, rispettivamente alla base e al tetto del GHS stesso. In questa tesi ho studiato l’evoluzione strutturale e geocronologica del STDS e della MCTz, con particolare focus su quest’ultima, in due transetti nell’Himalaya indiana occidentale: le valli dell’Alaknanda – Dhauli Ganga e la valle del Bhagirathi – Gangotri nella regione del Garhwal. A questo scopo, ho adottato un approccio multidisciplinare che combina studi microstrutturali, chimici e geocronologici e stime di vorticità cinematica. Poiché le miche sono ubiquitarie nelle zone di taglio, il metodo geocronologico 40Ar/39Ar su biotitie e muscovite è stato ampiamente utilizzato in passato e viene utilizzato tutt’oggi per vincolare l’età della deformazione per taglio. Il metodo 40Ar/39Ar step-heating, il più adatto per questo tipo di studi, è un metodo chiave per risolvere complessità petrologiche e chimiche grazie al riconoscimento di età differenti dovute a un differente rilascio dell’Ar caratterizzato da diversi rapporti Cl/K e Ca/K. Ho applicato questo metodo, combinato con una nuova procedura, l’Ar Differential Release Plot (DRP), che permette di identificare chiaramente l’influenza della coesistenza di fillosilicati nel trend di rilascio dell’Ar durante gli step di riscaldamento, permettendo di selezionare gli step ottimali che corrispondono al degassamento delle miche in senso stretto. Questa nuova procedura permette di determinare l’età in modo molto più accurato in rocce polideformate come quelle studiate. I risultati ottenuti con il metodo 40Ar/39Ar supportano la diacronicità della MCTz e del STDS nelle aree studiate, suggerendo che i modelli di esumazione del GHS dovrebbero tener conto della mancanza di contemporaneità tra queste due strutture. Inoltre, è stato sviluppato un nuovo approccio tridimensionale basato sulla X-ray micro Computed Tomography (microCT) e applicato per lo studio della vorticità cinematica usando il metodo dei porfiroclasti stabili. Un esame dei dati di letteratura ha dimostrato che il nostro approccio nello studio di vorticità usando il metodo dei porfiroclasti stabili non era mai stato applicato prima. Questo metodo è stato applicato a rocce provenienti dalla MCTz nella valle del Bhagirathi e i risultati suggeriscono che l’esumazione del GHS sia stata guidata da una variazione di deformazione all’interno della MCTz da un deformazione dominata da taglio semplice a cui è seguita una deformazione dominata da taglio puro, coerentemente con i dati di letteratura lungo la catena. Riassumendo, combinando studi meso e microstrutturali con analisi chimiche e geocronologia 40Ar/39Ar, i risultati della mia tesi indicano che la MCTz e il STDS non sono coevi nei transetti studiati e che la MCTz mostra una variazione di regime deformativo durante la sua evoluzione.
The Himalaya is commonly regarded as a cylindrical belt from west to east due to the impressive lateral continuity of the main litho-tectonic units and faults/shear zones, which is a peculiar feature of this mountain range. The exhumation of the metamorphic core of the belt, the Greater Himalayan Sequence (GHS), was favored by two regional scale opposite-kinematics ductile to brittle shear zones: the contractional Main Central Thrust zone (MCTz) at the bottom and the normal-sense South Tibetan Detachment System (STDS) at the top of the GHS itself. In this thesis, I investigated the structural and geochronological evolution of the STDS and the MCTz, with a particular focus on the latter, in two transects in the Indian Western Himalaya: the Alaknanda – Dhauli Ganga Valleys and the Bhagirathi – Gangotri Valley in the Garhwal region. To this aim, I used a multidisciplinary approach, which combines microstructural, chemical and geochronological studies, as well as a kinematic estimate. As micas are ubiquitous in strongly deformed shear zones, the 40Ar/39Ar geochronological method on biotite and muscovite has commonly been employed to constrain the ages of mylonitization. The 40Ar/39Ar step-heating approach, the most useful for the present study, is a key procedure to unravel petrological and chemical complexities because of the recognition of different ages due to different steps of Ar release characterized by different Cl/K and Ca/K ratios. I applied this method, combined with a new methodological approach first developed in detail during this Ph.D. thesis work, to rocks coming from the bounding shear zones of the GHS. This new procedure, named Ar Differential Release Plot (DRP), that allows to clearly identify the influence of the co-existence of phyllosilicates on the trend of Ar release during the heating steps, allowing to select the optimal steps corresponding to the degassing of micas sensu stricto, which leads to more reliable age determinations in such metamorphic polydeformed rocks. The results of 40Ar/39Ar method support the diachroneity of the MCTz and the STDS in the studied areas, suggesting that the models of exhumation of the GHS should account for their lack of contemporaneity. Moreover, a new three-dimensional approach based on the X-ray micro Computed Tomography (microCT) has been developed and applied for the study of the kinematic vorticity using the stable porphyroclasts method. A close examination of literature data shows that our study approach in the study of kinematic vorticity using the microCT has never been applied before. This method has been applied to MCTz rocks from the Bhagirathi valley and the results suggest that the exhumation of the GHS has been affected by a shift of deformation within the MCTz from simple to pure shear dominated flow, coherent with literature data all along the belt. In summary, combining meso‐ and micro‐structural studies as well as chemical analyses and 40Ar/39Ar geochronology, my thesis results points out how MCTz and STDS are not coeval in the studied structural transects and that the MCTz shows a shift in deformation regime during its evolution.
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3

Little, L. Nicole. "Characterization of Basigin and the Interaction Between Embigin and Monocarboxylate Transporter -1, -2, and -4 (MCT1, MCT2, MCT4) in the Mouse Brain." UNF Digital Commons, 2011. http://digitalcommons.unf.edu/etd/384.

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Basigin and Embigin are members of the immunoglobulin superfamily that function as cell adhesion molecules. Studies of Basigin null mice revealed reproductive sterility, increased pain sensitivity, and blindness. It is thought that the mechanism causing blindness involves misexpression of monocarboxylate transporter 1 (MCT1) in the absence of Basigin. It is known that the transmembrane domain of Basigin interacts with MCT1. In the absence of Basigin, MCT1 does not localize to the plasma membrane of expressing cells and photoreceptor function is disrupted. Studies of the Basigin null mouse brain suggest that MCT1 is properly expressed, which suggests a separate mechanism causes the increased pain sensitivity in these animals, and also that a different protein directs MCT1 to the plasma membrane of expressing cells in mouse brain. Embigin is known to interact with MCT2 in neurons and with MCT1 in erythrocytes. It is not known, however, if Embigin normally interacts with MCT1 in the mouse brain or if Embigin acts to compensate for the lack of Basigin in the Basigin null animals. Therefore, the purpose of this study was to determine if Embigin normally interacts with MCT1, 2, or 4 in the mouse brain and if so, whether the interaction is similar to that between Basigin and MCT1. Expression of Basigin, Embigin, MCT1, MCT2, and MCT4 in mouse brain was assessed via immunoblotting and immunohistochemical analyses. In addition, recombinant protein probes corresponding to the Embigin transmembrane domain were generated for ELISA binding assays using endogenous mouse brain MCTs. It was determined that the proteins in question are rather ubiquitously expressed throughout the mouse brain, and that the cell adhesion molecules Basigin and Embigin may be co-expressed in the same cells as the MCT2 and MCT4 transporter proteins. In addition, it was determined that the Embigin transmembrane domain does not interact with the MCTs. The data therefore suggest that MCTs do not require Basigin or Embigin for plasma membrane expression in mouse brain.
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4

Richards, William. "The influence of aging and cardiovascular training status upon monocarboxylate transporters." Columbus, Ohio : Ohio State University, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1133362045.

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5

Feringer, Júnior Walter Heinz [UNESP]. "Expressão dos transportadores de monocarboxilatos de equinos e cães." Universidade Estadual Paulista (UNESP), 2017. http://hdl.handle.net/11449/153171.

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O principal mecanismo de transporte dos íons lactato e H+ em equinos e cães é o complexo transportador formado pelos transportadores de monocarboxilatos, isoformas 1 (MCT1) e 4 (MCT4) juntamente com a proteína auxiliar CD147. Objetivando identificar diferenças entre equinos com desempenho distinto, 16 equinos da raça Brasileiro de Hipismo (BH) foram distribuídos em dois grupos, desempenho inferior (DI, n=8) e desempenho superior (DS, n=8) que foram submetidos a teste de salto incrementai (TSI). Realizou-se biópsia do músculo Gluteus medius para tipificação e análise das expressões das isoformas MCT1, MCT4 e CD147. Amostras sanguíneas foram colhidas para avaliar as expressões MCT1 e CD147 das hemácias. Aplicaram-se testes de normalidade de Shapiro Wilk e homogeneidade de Levene. As medidas morfométricas foram submetidas ao teste de Tukey. Teste “t” de Student não pareado para a comparação das médias dos grupos DI e DS. Aplicou-se correlação de Spearman para as expressões dos transportadores. Para todas as análises utilizou-se p≤0,05. Não houve diferença entre os grupos quanto à frequência de cada tipo de fibra e constatou-se maior quantidade das fibras tipo I em relação às fibras IIA e IIX em todos os equinos avaliados. Não houve diferença entre os pesos moleculares e a expressão das proteínas MCT1, MCT4, e CD147 musculares ou sanguíneas. Houve correlações positivas entre MCT1 vs. CD147 e MCT4 vs. CD147 musculares dos grupos DI e DS. As correlações encontradas foram esperadas uma vez que as isoformas estudadas dependem intimamente da proteína auxiliar CD147 para o transporte. Os equinos BH não apresentaram diferenças nas expressões dos MCT1,4 e CD147, musculares ou sanguíneos, mesmo com níveis de condicionamento diferentes. Com o objetivo de investigar as concentrações de lactato plasmático e das hemácias e avaliar as expressões eritrocitáras do complexo transportador MT1/CD147, 6 cães da raça American Pitbull Terrier (APBT) foram submetidos ao teste de esforço incremental (TEI) em esteira. No final de cada incremento de velocidade foi coletado sangue da veia cefálica. Foram mensuradas concentrações de lactato sanguíneo (LS), plasmático (LP), pH e hematócrito (Ht). A concentração do lactato dentro das hemácias (LH) foi estimada e estabeleceu-se a relação LH:LP. As expressões sanguíneas do complexo MCT1/CD147 foram avaliadas por Western Bloting. Aplicou-se análise de variância de uma via seguido pelo teste de Dunn’s. Para pH e Ht aplicou-se teste t de student para amostras pareadas e a correlação de Pearson foi utilizada para MCT1 e CD147, estabeleceu-se nível de significância P≤0,05. LS, LP e LH e pH não apresentaram diferenças entre si, a relação LH:LP foi próxima de 1 com tendência de aumento. MCT1 e CD147 apresentaram 48 e 59 kDa de peso molecular e 1,27 e 1,05 de unidades ópticas arbitrárias (UOA). Não foram encontradas correlações entre MCT1 e CD147. A grande velocidade de transporte do MCT1/CD147 explica a relação LP:LH próxima de 1, esta velocidade e o mecanismo de arquejo podem explicar os valores de pH constantes. A raça APBT, quando submetidos à atividade física apresentaram tendência de aumento da relação LH:LP e expressam de maneira homogênea o complexo MCT1/CD147.
The central transport mechanism of lactate and H+ ions in horses and dogs is the carrier complex formed by the monocarboxylate, isoform 1 (MCT1) and 4 (MCT4) associated with the ancillary protein CD147. This study aimed to identify possible differences between horses with different performances levels, 16 horses of the Brazilian Sport Horse breed (BH) were distributed in two groups, inferior performance (IP, n = 8) and superior performance (SP, n = 8). A Gluteus medius muscle biopsy was performed for cellular typing and analysis of MCT1, MCT4, and CD147 muscle expressions. By jugular venipuncture, blood samples were collected to evaluate MCT1 and CD147 expressions in the red blood cells (RBC). Normality Shapiro Wilk test and homogeneity of Levene were applied. The morphometric measurements were submitted to the Tukey test, and not paired Student's t-test were applied to compare the mean of the IP and SP groups for all variables and was used Spearman's correlation for isoform expressions, for all analyzes, p≤0.05. There were no differences between the groups regarding the frequency of each type of fiber and a higher number of type I fibers were observed about the IIA and IIX fibers in all groups. There was no difference between molecular weights and expressions of MCT1, MCT4, and CD147 in muscle or blood. There were positive correlations between muscles MCT1 vs CD147 and MCT4 vs CD147 in both groups. The relationships found were expected since the MCT1 and 4 depended on the CD147 ancillary protein for correct functioning. The BH horses do not present differences in the muscle or RBC expressions of MCT1, 4 and CD147, even with different conditioning levels. To investigate plasma and erythrocyte lactate concentrations and to evaluate erythrocyte expression of the MT1/CD147 transporter complex, six dogs of the American Pit Bull Terrier breed (APBT) were submitted to a treadmill incremental effort test (IET). At the end of each increment of speed, blood was collected from the cephalic vein. Concentrations of blood (BL) and plasma lactate (PL), pH and hematocrit (Ht) were measured. The concentration of lactate inside the red blood cells (LC) was estimated and the LC: PL ratio was established, the blood expressions of the MCT1/CD147 transporter complex were evaluated by western blot. Data were submitted to the Shapiro-Wilks normality test, one-way ANOVA and Dunn's test. For pH and Ht, paired Student's t-test was applied, and Pearson's correlation was used for MCT1 and CD147 analysis, for all analyzes, p≤0.05. BL, PL, LC, pH showed no differences, the LC: PL ratio was close to 1 with an increasing tendency. MCT1 and CD147 presented 48 and 59 kDa of molecular weight and 1.27 and 1.05 of arbitrary optical units (AOU). No correlations were found between MCT1 and CD147. The high transport velocity of the MCT1/CD147 could explain the LC: PL ratio close to 1, this velocity plus the grasping mechanism may explain the constant of pH values. The APBT submitted to intense physical activity showed a tendency to increase the LC: PL ratio, and homogeneously express the MCT1/CD147 complex
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Feringer-Junior, Walter Heinz. "Expressão dos transportadores de monocarboxilatos de equinos e cães /." Jaboticabal, 2017. http://hdl.handle.net/11449/153171.

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Orientador: Guilherme de Camargo Ferraz
Resumo: O principal mecanismo de transporte dos íons lactato e H+ em equinos e cães é o complexo transportador formado pelos transportadores de monocarboxilatos, isoformas 1 (MCT1) e 4 (MCT4) juntamente com a proteína auxiliar CD147. Objetivando identificar diferenças entre equinos com desempenho distinto, 16 equinos da raça Brasileiro de Hipismo (BH) foram distribuídos em dois grupos, desempenho inferior (DI, n=8) e desempenho superior (DS, n=8) que foram submetidos a teste de salto incrementai (TSI). Realizou-se biópsia do músculo Gluteus medius para tipificação e análise das expressões das isoformas MCT1, MCT4 e CD147. Amostras sanguíneas foram colhidas para avaliar as expressões MCT1 e CD147 das hemácias. Aplicaram-se testes de normalidade de Shapiro Wilk e homogeneidade de Levene. As medidas morfométricas foram submetidas ao teste de Tukey. Teste “t” de Student não pareado para a comparação das médias dos grupos DI e DS. Aplicou-se correlação de Spearman para as expressões dos transportadores. Para todas as análises utilizou-se p≤0,05. Não houve diferença entre os grupos quanto à frequência de cada tipo de fibra e constatou-se maior quantidade das fibras tipo I em relação às fibras IIA e IIX em todos os equinos avaliados. Não houve diferença entre os pesos moleculares e a expressão das proteínas MCT1, MCT4, e CD147 musculares ou sanguíneas. Houve correlações positivas entre MCT1 vs. CD147 e MCT4 vs. CD147 musculares dos grupos DI e DS. As correlações encontradas foram esperadas ... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The central transport mechanism of lactate and H+ ions in horses and dogs is the carrier complex formed by the monocarboxylate, isoform 1 (MCT1) and 4 (MCT4) associated with the ancillary protein CD147. This study aimed to identify possible differences between horses with different performances levels, 16 horses of the Brazilian Sport Horse breed (BH) were distributed in two groups, inferior performance (IP, n = 8) and superior performance (SP, n = 8). A Gluteus medius muscle biopsy was performed for cellular typing and analysis of MCT1, MCT4, and CD147 muscle expressions. By jugular venipuncture, blood samples were collected to evaluate MCT1 and CD147 expressions in the red blood cells (RBC). Normality Shapiro Wilk test and homogeneity of Levene were applied. The morphometric measurements were submitted to the Tukey test, and not paired Student's t-test were applied to compare the mean of the IP and SP groups for all variables and was used Spearman's correlation for isoform expressions, for all analyzes, p≤0.05. There were no differences between the groups regarding the frequency of each type of fiber and a higher number of type I fibers were observed about the IIA and IIX fibers in all groups. There was no difference between molecular weights and expressions of MCT1, MCT4, and CD147 in muscle or blood. There were positive correlations between muscles MCT1 vs CD147 and MCT4 vs CD147 in both groups. The relationships found were expected since the MCT1 and 4 depended on the CD... (Complete abstract click electronic access below)
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Benesch, Franziska. "Regulative Einflüsse auf die Monocarboxylattransporter 1 und 4 im Pansenepithel des Schafes." Doctoral thesis, Universitätsbibliothek Leipzig, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-211226.

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Einleitung: Monocarboxylattransporter (MCT) 1 & 4 sind in zahlreichen Geweben als Kotransporter für Monocarboxylate und Protonen beschrieben. Auch im Pansenepithel werden MCT benötigt, um kurzkettige Fettsäuren (SCFA) aus dem Pansenlumen in die Pansenepithelzelle aufzunehmen (MCT4) und um SCFA und deren Metabolite aus der Pansenepithelzelle in das Blut auszuschleusen (MCT1). Die transepitheliale Permeation von SCFA über die Pansenwand ist von enormer Bedeutung, da sie die wichtigste Energiequelle der Wiederkäuer darstellen. Die beteiligten Transportprozesse müssen dementsprechend einer Anpassung an variierende Mengen von SCFA unterliegen. Bisherige Studien bei anderen Spezies deuten auf eine Regulation des MCT1 auf mRNA Ebene über den Peroxisom-Proliferator-aktivierten Rezeptor α (PPARα) hin. Ziele der Untersuchung: Das Ziel dieser Arbeit war herauszufinden, ob MCT1 in ovinen Pansenepithelzellen über PPARα reguliert wird und ob auch MCT4 dieser Regulation unterliegt. Eine gleichzeitige Regulation beider Transporter läge nahe, da sie gemeinsam an der transepithelialen Permeation beteiligt sind. Die Auswirkungen solch einer Regulation auf die Proteinexpression und die Transportleistung der MCT sollte charakterisiert werden. Ebenfalls war das Potenzial der bei erhöhter Kraftfutterfütterung vermehrt anfallenden SCFA Butyrat auf die MCT1 Expression zu untersuchen. Material & Methoden: Aus dem Vorhof von Schafen wurden Pansenepithelzellen gewonnen und entsprechend einer bereits etablierten Methode kultiviert. Nach einer Subkultivierung wurden die Zellen immunzytochemisch mit Antikörpern gegen MCT1, MCT4 und Na+/K+-ATPase untersucht, um deren Lokalisation in den kultivierten Pansenepithelzellen zu bestimmen. Weiterhin erfolgte eine Behandlung mit WY 14.643, einem spezifischen, synthetischen PPARα Agonisten, sowie mit GW 6471, einem Antagonisten des PPARα. Mittels qPCR wurden die relativen mRNA Mengen von MCT1, MCT4, ACO, CPT1A und CACT bestimmt und auf die Referenzgene GAPDH und Na+/K+-ATPase normalisiert. Die Proteinexpression von MCT1 und MCT4 wurde mittels Western Blot bestimmt. Zur funktionellen Quantifizierung wurde der intrazelluläre pH-Wert der Zellen mittels Spektrofluorometrie gemessen und der laktatabhängige Protonentransport als Vergleichswert zwischen den Behandlungen genutzt. Um den MCT-abhängigen Teil des Transportes zu bestimmen, wurde ein spezifischer MCT1 & 4 Inhibitor, die p-Hydroxymercuribenzensulfonsäure (pHMB) eingesetzt. Die Zellen wurden mit Butyrat über einen Zeitraum von 6 und 48 h induziert. Die Erfassung der MCT1 Expression erfolgte mittels semiquantitativer PCR. Ergebnisse: MCT1 & 4 sind sowohl in der Zellmembran als auch intrazellulär in den Pansenepithelzellen lokalisiert. Die mRNA Expressionsdaten konnten zeigen, dass MCT1 und die PPARα Zielgene durch WY 14.643 hochreguliert werden konnten, wohingegen die MCT4 Expression keine eindeutige Antwort auf die Stimulation zeigt. Die Behandlung mit den Antagonisten zeigt eine Abhängigkeit der MCT1 Expression von PPARα, die MCT4 Expression konnte dagegen nicht beeinflusst werden. Mittels pHMB gelang es, den laktatabhängigen Protonenexport fast vollständig zu blocken. Sowohl laktatabhängiger Protonenexport als auch die Proteinexpression zeigten keine Änderung durch WY 14.643 Stimulation. Die Butyratexposition veränderte die Morphologie der Pansenepithelzellen und schien nicht geeignet für Untersuchungen der mRNA Expression zu sein. Schlussfolgerungen: Es konnte in dieser Arbeit erstmals gezeigt werden, dass MCT1 in Pansenepithelzellen über PPARα reguliert wird, nicht aber MCT4. PPARα scheint demnach einer der entscheidenden Angriffspunkte für die Regulation des SCFA Transportes zu sein, dessen natürliche Liganden im Pansen aber noch nicht bekannt sind. Damit legt diese Arbeit den Grundstein für regulative Studien am intakten Pansenepithel
Introduction: Monocarboxylate transporters (MCT) 1 & 4 are cotransporters of monocarboxylates and protons in a variety of mammalian cell types. In the ruminal epithelium MCT are necessary to transport short-chain fatty acids (SCFA) from the lumen into the ruminal epithelial cell (MCT4) and to discharge SCFA and their metabolites from the cell into the blood (MCT1). Transepithelial permeation of SCFA is of great importance, because they are the main source of energy for ruminants. The regulation of appropriate transport proteins should thus be subject to the adaptation to varying SCFA amounts. Previous studies in other species suggested that gene expression of MCT1 is regulated by peroxisome proliferator-activated receptor α (PPARα), a ligand-activated nuclear receptor. Aims: The aim of the study was to examine if MCT1 in ruminal epithelial cells is regulated by PPARα and furthermore if MCT4 can be regulated by PPARα, as well. A simultaneous regulation seems likely, because both are acting jointly in the transepithelial transporting of SCFA. The implications of such a regulation on protein expression and transport capacity of MCT should be characterized. The effect of butyrate, a SCFA which increases under concentrate feeding, on MCT1 expression was determined. Materials & Methods: Ruminal epithelial cells of sheep were cultivated according to methods previously established. After subcultivation, immunocytochemistry with antibodies against MCT1, MCT4 and Na+/K+-ATPase was performed to determine their localization in ruminal epithelial cells. For studying the influence of PPARα, WY 14.643, a synthetic and selective ligand of PPARα, and GW 6471, a synthetic antagonist of PPARα, were applied to the culture medium of the cells. After processing the specimens, the relative amount of mRNA of MCT1, MCT4 and the target genes ACO, CPT1A and CACT were analyzed by qPCR and normalized on the reference genes GAPDH and Na+/K+-ATPase. Protein abundance of MCT1 & 4 was measured by using the Western Blot method. Functional quantification was measured by the intracellular pH (pHi) of cells using spectrofluorometry as well as comparing the effect of WY 14.643 treatment on lactate-dependent proton export. To determine the MCT-dependent part of the pHi recovery, p-hydroxymercuribenzoic acid (pHMB), a specific inhibitor of MCT1 & 4, was applied. Cells were also treated with butyrate for 6 h and 48 h and the mRNA abundance of MCT1 was analyzed by semiquantitative PCR. Results: Both MCT1 and MCT4 were localized in the cell membrane as well as in the cytoplasm of ruminal epithelial cells. By qPCR it could be demonstrated that the mRNA abundance of MCT1 and PPARα target genes in the ruminal epithelial cells was increased by WY 14.643 in comparison to untreated cells, whereas the response of MCT4 did not yield distinct results. Treatment with the PPARα antagonist pointed out, that MCT1 is influenced by PPARα, but not MCT4. Lactate-dependent proton export was blocked almost completely by pHMB. Both lactate-dependent proton export and protein expression were not altered by WY 14.643 treatment. Butyrate exposure changed the morphology of ruminal epithelial cells and seemed unsuitable for the analysis of mRNA expression. Conclusion: For the first time, it could be demonstrated, that MCT1 in ruminal epithelial cells is regulated by PPARα, but not MCT4. PPARα seems to be a vital target in the rumen for SCFA transport regulation, whose natural triggers have yet to be identified. Furthermore, this study provides the basis for regulative studies on intact ruminal epithelium
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Manoharan, Christine. "The molecular basis for the interaction between MCT1 and MCT2 with the ancillary proteins CD147 and GP70." Thesis, University of Bristol, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.417644.

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Hutchinson, Laura. "The role and therapeutic significance of monocarboxylate transporters in prostate cancer." Thesis, University of Manchester, 2017. https://www.research.manchester.ac.uk/portal/en/theses/the-role-and-therapeutic-significance-of-monocarboxylate-transporters-in-prostate-cancer(280f6221-d12b-4ca9-9322-e0ba1f5511f6).html.

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It has been shown that tumour cells are capable of switching to glycolytic metabolism for the production of ATP even in the presence of oxygen, this is known as aerobic glycolysis or the 'Warburg effect'. The glycolytic phenotype has been associated with tumour aggressiveness and poor outcome in several cancer types. This makes the area of cancer metabolism an attractive area for the potential identification of new therapeutic targets. One key component, required for cells to maintain the glycolytic phenotype, is the presence of monocarboxylate transporters that are capable of exporting lactate. These transporters are vital for the maintenance of the intracellular pH of cells under these conditions. This study was centred around the hypothesis that altering expression of MCTs would impact on the metabolism of tumour cells and, therefore, other key characteristics of cells relating to metastatic capabilities and survival following treatment. For the purpose of this work, prostate cancer cell lines were transfected with lentiviral particles targeting overexpression of MCT1 or MCT4, or knockdown of MCT4. Following transfection, cellular metabolic profiles were assessed under normoxic and hypoxic conditions and the metastatic phenotype of each cell line was investigated. Additionally, the effect of MCT expression on response to chemotherapy and radiation therapy was explored, and a siRNA metabolome screen was performed to identify combinations of targets that may produce synthetic lethality in prostate cancer cell lines. It was shown that changes in the expression of MCT1 or MCT4 did not cause significant changes in the metastatic phenotypes of the prostate cancer cell lines investigated. Some differences were observed in the metabolic pathways used by these prostate cancer cells following alterations in MCT expression. For example, overexpression of MCT1 in DU145 cells resulted in an increase in intracellular lactate. Additionally, MCT4 knockdown in PC3 cells was able to reduce OXPHOS under reduced oxygen. MCT1 overexpression was able to sensitise androgen-independent prostate cancer cells to treatment with chemotherapy and radiation therapy. Furthermore, combinations of siRNA treatments were identified that may be capable of producing synthetic lethality. In summary, findings in this study indicated that targeting MCT1 and MCT4 expression could offer therapeutic benefit in prostate cancer. However, it was also highlighted that the roles of these transporters are specific to cancer type, and even cell line.
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Py, Guillaume. "Étude du transport sarcolemmal du lactate et de l'expression des isoformes MCT1 et MCT4 chez le rat diabétique et Zucker fa/fa." Montpellier 1, 2001. http://www.theses.fr/2001MON1T014.

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Le lactate a longtemps ete considere comme un produit final de la glycolyse et le temoin d'une limitation de l'apport en oxygene au niveau des tissus. Durant les vingt dernieres annees, grace au developpement de nouvelles techniques, des travaux ont permis de montrer que le lactate etait produit en condition d'oxygenaton normale et que celui-ci etait le substrat neoglucogenique de choix au niveau hepatique. Associe aux anomalies du metabolisme du glucose, l'etat de diabete et d'insulinoresistance sont caracterises par des lactatemies basales anormalement elevees. L'origine de ces niveaux eleves de lactate est encore mal definie. Nous avons, dans ce travail, mis en evidence des alterations des echanges sarcolemmaux du lactate dans des modeles animaux de diabete et d'obesite, a l'aide d'un modele subcellulaire que sont les vesicules de sarcolemme. [. . . ] ainsi, meme si les alterations de l'activite de transport du lactate dans le diabete de type 1 ne trouvent pas leur explication dans l'expression des isoformes musculaires de mct, il semble aux vues de donnees recentes, que ceux-ci soient quand meme impliques dans la diminution de la clearance du lactate. A la difference, la perturbation musculaire des echanges et du metabolisme du lactate dans l'obesite pourrait participer a l'etat d'insulinoresistance.
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Books on the topic "MCTz"

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Cattini, Roland. Windows 7: Microsoft Certified Technology Specialist und IT Professional ; [Vorbereitung auf die Pru fungen #70-680, #70-682 und #70-685]. Heidelberg: mitp, 2010.

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Mathematics Curriculum and Teaching Program. MCTP: Professional development package. Canberra: Curriculum Development Centre, 1988.

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MCTL, militarily critical technologies list. [Fort Belvoir, Va.]: [Defense Technical Information Center], 1996.

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(Firm), Harris Semiconductor. MCT/IGBTs/diodes. Melbourne, Florida: Harris Semiconductor, 1994.

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Darwin, Charles. MCZ Kindle 1. Seattle, WA: Amazon.com, 2009.

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Ramiro, Villarreal, and United States. National Aeronautics and Space Administration., eds. MCT crystal growth. [Washington, DC: National Aeronautics and Space Administration, 1988.

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Leon, Plesniarski, ed. MCTS guide to Microsoft Windows 7. Australia: Cengage Learning, 2011.

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Poulton, Don. MCTS 70-620: Microsoft Windows Vista, configuring. Indianapolis, Ind: Que Pub., 2008.

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Byron, Wright, ed. MCTS guide to Microsoft Windows Vista Professional. Boston, Mass: ThomsonCourse Technology, 2008.

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Stidley, Joel. MCTS: Microsoft Exchange Server 2007 Configuration Study Guide. New York: John Wiley & Sons, Ltd., 2009.

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Book chapters on the topic "MCTz"

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Oette, Mark, Marvin J. Stone, Hendrik P. N. Scholl, Peter Charbel Issa, Monika Fleckenstein, Steffen Schmitz-Valckenberg, Frank G. Holz, et al. "MCTD." In Encyclopedia of Molecular Mechanisms of Disease, 1270. Berlin, Heidelberg: Springer Berlin Heidelberg, 2009. http://dx.doi.org/10.1007/978-3-540-29676-8_6275.

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Hutchins, Tiffany, Giacomo Vivanti, Natasa Mateljevic, Roger J. Jou, Frederick Shic, Lauren Cornew, Timothy P. L. Roberts, et al. "MCT." In Encyclopedia of Autism Spectrum Disorders, 1813. New York, NY: Springer New York, 2013. http://dx.doi.org/10.1007/978-1-4419-1698-3_100859.

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Baliga, B. Jayant. "Silicon MCT." In Advanced High Voltage Power Device Concepts, 385–436. New York, NY: Springer New York, 2011. http://dx.doi.org/10.1007/978-1-4614-0269-5_8.

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Shahid, Azmeh, Kate Wilkinson, Shai Marcu, and Colin M. Shapiro. "Munich Chronotype Questionnaire (MCTQ)." In STOP, THAT and One Hundred Other Sleep Scales, 245–47. New York, NY: Springer New York, 2011. http://dx.doi.org/10.1007/978-1-4419-9893-4_58.

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Capper, P. "MCT Materials Aspects." In Infrared Detectors and Emitters: Materials and Devices, 251–78. Boston, MA: Springer US, 2001. http://dx.doi.org/10.1007/978-1-4615-1607-1_10.

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Nahler, Gerhard. "multicentre trial (MCT)." In Dictionary of Pharmaceutical Medicine, 116–17. Vienna: Springer Vienna, 2009. http://dx.doi.org/10.1007/978-3-211-89836-9_884.

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Gartenhaus, Ronald B., and Ari L. Landon. "MCT-1 Oncogene." In Encyclopedia of Cancer, 1–2. Berlin, Heidelberg: Springer Berlin Heidelberg, 2015. http://dx.doi.org/10.1007/978-3-642-27841-9_3578-2.

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Gartenhaus, Ronald B., and Ari L. Landon. "MCT-1 Oncogene." In Encyclopedia of Cancer, 2683–84. Berlin, Heidelberg: Springer Berlin Heidelberg, 2015. http://dx.doi.org/10.1007/978-3-662-46875-3_3578.

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Gartenhaus, Ronald B. "MCT-1 Oncogene." In Encyclopedia of Cancer, 2193–94. Berlin, Heidelberg: Springer Berlin Heidelberg, 2011. http://dx.doi.org/10.1007/978-3-642-16483-5_3578.

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Shaw, D. "Diffusion in MCT." In Mercury Cadmium Telluride, 239–62. Chichester, UK: John Wiley & Sons, Ltd, 2010. http://dx.doi.org/10.1002/9780470669464.ch10.

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Conference papers on the topic "MCTz"

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Eilertsen, Marte, Sigve Andersen, Samer Al-Saad, Yury Kiselev, Tom Donnem, Helge Stenvold, Khalid Al-Shibli, Elin Richardsen, Lill-Tove Busund, and Roy Martin Bremnes. "Abstract 2377: MCT1 and MCT4 in NSCLC: Overexpression of MCT1 in tumor and stroma is an independent prognostic marker for NSCLC survival." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-2377.

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Sharma, Sambad, Gregory Goreczny, Satish Kumar Noonepalle, Erica Palmer, Maria Garcia-Hernandez, Daliya Banerjee, Jaime Escobedo, Alejandro Villagra, and Vincent Sandanayaka. "Abstract 1268: A novel treatment approach for melanoma by dually targeting MCT1 and MCT4 lactate transporters." In Proceedings: AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/1538-7445.am2021-1268.

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Lan, Li-Cheng, Wei Li, Ting-Han Wei, and I.-Chen Wu. "Multiple Policy Value Monte Carlo Tree Search." In Twenty-Eighth International Joint Conference on Artificial Intelligence {IJCAI-19}. California: International Joint Conferences on Artificial Intelligence Organization, 2019. http://dx.doi.org/10.24963/ijcai.2019/653.

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Many of the strongest game playing programs use a combination of Monte Carlo tree search (MCTS) and deep neural networks (DNN), where the DNNs are used as policy or value evaluators. Given a limited budget, such as online playing or during the self-play phase of AlphaZero (AZ) training, a balance needs to be reached between accurate state estimation and more MCTS simulations, both of which are critical for a strong game playing agent. Typically, larger DNNs are better at generalization and accurate evaluation, while smaller DNNs are less costly, and therefore can lead to more MCTS simulations and bigger search trees with the same budget. This paper introduces a new method called the multiple policy value MCTS (MPV-MCTS), which combines multiple policy value neural networks (PV-NNs) of various sizes to retain advantages of each network, where two PV-NNs f_S and f_L are used in this paper. We show through experiments on the game NoGo that a combined f_S and f_L MPV-MCTS outperforms single PV-NN with policy value MCTS, called PV-MCTS. Additionally, MPV-MCTS also outperforms PV-MCTS for AZ training.
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Baier, Hendrik, and Michael Kaisers. "ME-MCTS: Online Generalization by Combining Multiple Value Estimators." In Thirtieth International Joint Conference on Artificial Intelligence {IJCAI-21}. California: International Joint Conferences on Artificial Intelligence Organization, 2021. http://dx.doi.org/10.24963/ijcai.2021/555.

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This paper addresses the challenge of online generalization in tree search. We propose Multiple Estimator Monte Carlo Tree Search (ME-MCTS), with a two-fold contribution: first, we introduce a formalization of online generalization that can represent existing techniques such as "history heuristics", "RAVE", or "OMA" -- contextual action value estimators or abstractors that generalize across specific contexts. Second, we incorporate recent advances in estimator averaging that enable guiding search by combining the online action value estimates of any number of such abstractors or similar types of action value estimators. Unlike previous work, which usually proposed a single abstractor for either the selection or the rollout phase of MCTS simulations, our approach focuses on the combination of multiple estimators and applies them to all move choices in MCTS simulations. As the MCTS tree itself is just another value estimator -- unbiased, but without abstraction -- this blurs the traditional distinction between action choices inside and outside of the MCTS tree. Experiments with three abstractors in four board games show significant improvements of ME-MCTS over MCTS using only a single abstractor, both for MCTS with random rollouts as well as for MCTS with static evaluation functions. While we used deterministic, fully observable games, ME-MCTS naturally extends to more challenging settings.
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Zhang, Yunsheng, Dong Yan, Bei Shi, Haobo Fu, Qiang Fu, Hang Su, Jun Zhu, and Ning Chen. "Combining Tree Search and Action Prediction for State-of-the-Art Performance in DouDiZhu." In Thirtieth International Joint Conference on Artificial Intelligence {IJCAI-21}. California: International Joint Conferences on Artificial Intelligence Organization, 2021. http://dx.doi.org/10.24963/ijcai.2021/470.

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AlphaZero has achieved superhuman performance on various perfect-information games, such as chess, shogi and Go. However, directly applying AlphaZero to imperfect-information games (IIG) is infeasible, due to the fact that traditional MCTS methods cannot handle missing information of other players. Meanwhile, there have been several extensions of MCTS for IIGs, by implicitly or explicitly sampling a state of other players. But, due to the inability to handle private and public information well, the performance of these methods is not satisfactory. In this paper, we extend AlphaZero to multiplayer IIGs by developing a new MCTS method, Action-Prediction MCTS (AP-MCTS). In contrast to traditional MCTS extensions for IIGs, AP-MCTS first builds the search tree based on public information, adopts the policy-value network to generalize between hidden states, and finally predicts other players' actions directly. This design bypasses the inefficiency of sampling and the difficulty of predicting the state of other players. We conduct extensive experiments on the popular 3-player poker game DouDiZhu to evaluate the performance of AP-MCTS combined with the framework AlphaZero. When playing against experienced human players, AP-MCTS achieved a 65.65\% winning rate, which is almost twice the human's winning rate. When comparing with state-of-the-art DouDiZhu AIs, the Elo rating of AP-MCTS is 50 to 200 higher than them. The ablation study shows that accurate action prediction is the key to AP-MCTS winning.
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Baier, Hendrik, and Mark H. M. Winands. "MCTS-Minimax Hybrids with State Evaluations (Extended Abstract)." In Twenty-Seventh International Joint Conference on Artificial Intelligence {IJCAI-18}. California: International Joint Conferences on Artificial Intelligence Organization, 2018. http://dx.doi.org/10.24963/ijcai.2018/782.

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Monte-Carlo Tree Search (MCTS) has been found to show weaker play than minimax-based search in some tactical game domains. In order to combine the tactical strength of minimax and the strategic strength of MCTS, MCTS-minimax hybrids have been proposed in prior work. This article continues this line of research for the case where heuristic state evaluation functions are available. Three different approaches are considered, employing minimax in the rollout phase of MCTS, as a replacement for the rollout phase, and as a node prior to bias move selection. The latter two approaches are newly proposed. Results show that the use of enhanced minimax for computing node priors results in the strongest MCTS-minimax hybrid in the three test domains of Othello, Breakthrough, and Catch the Lion. This hybrid also outperforms enhanced minimax as a standalone player in Breakthrough, demonstrating that at least in this domain, MCTS and minimax can be combined to an algorithm stronger than its parts.
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Bowman, Nicole, Sambad Sharma, Jennifer Duffy, Sanath Wijerathna, Nelly Kuklin, Jaime Escobedo, and Vincent Sandanayaka. "1381 Lactate modulation in cancer and immune cells is associated with antitumor efficacy of dual MCT1/MCT4 inhibitor NGY-091." In SITC 37th Annual Meeting (SITC 2022) Abstracts. BMJ Publishing Group Ltd, 2022. http://dx.doi.org/10.1136/jitc-2022-sitc2022.1381.

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Floch, Renaud Le, Johanna Chiche, Ibtissam Marchiq, Tanesha Naiken, Karine Ilc, Marie-Pierre Simon, Danièle Roux, and Jacques Pouyssegur. "Abstract 3225: Growth inhibition of glycolytic tumors by targeting basigin/lactate-H+ symporters (MCTs): Metformin sensitizes MCT inhibition." In Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-3225.

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Hu, Yong, Daniel Mueller-Gritschneder, and Ulf Schlichtmann. "Wavefront-MCTS." In ICCAD '18: IEEE/ACM INTERNATIONAL CONFERENCE ON COMPUTER-AIDED DESIGN. New York, NY, USA: ACM, 2018. http://dx.doi.org/10.1145/3240765.3240863.

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Gabor, Thomas, Jan Peter, Thomy Phan, Christian Meyer, and Claudia Linnhoff-Popien. "Subgoal-Based Temporal Abstraction in Monte-Carlo Tree Search." In Twenty-Eighth International Joint Conference on Artificial Intelligence {IJCAI-19}. California: International Joint Conferences on Artificial Intelligence Organization, 2019. http://dx.doi.org/10.24963/ijcai.2019/772.

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We propose an approach to general subgoal-based temporal abstraction in MCTS. Our approach approximates a set of available macro-actions locally for each state only requiring a generative model and a subgoal predicate. For that, we modify the expansion step of MCTS to automatically discover and optimize macro-actions that lead to subgoals. We empirically evaluate the effectiveness, computational efficiency and robustness of our approach w.r.t. different parameter settings in two benchmark domains and compare the results to standard MCTS without temporal abstraction.
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Reports on the topic "MCTz"

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Kandula, Rajendra Prasad, Deepak Divan, Rohit Jinsiwale, and Mickael Mauger. Modular Controllable Transformers (MCT). Office of Scientific and Technical Information (OSTI), June 2018. http://dx.doi.org/10.2172/1488762.

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Kent Perry, Samih Batarseh, Sheriff Gowelly, and Thomas Hayes. Field Demonstraton of Existing Microhole Coiled Tubing Rig (MCTR) Technology. Office of Scientific and Technical Information (OSTI), May 2006. http://dx.doi.org/10.2172/888550.

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Bart Patton. A Built for Purpose Micro-Hole Coiled Tubing Rig (MCTR). Office of Scientific and Technical Information (OSTI), September 2007. http://dx.doi.org/10.2172/924715.

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Teter, Michael, Arnold Buss, Christian Darken, and Ricardo Baez. Implementation of Monte Carlo Tree Search (MCTS) Algorithm in COMBATXXI using JDAFS. Fort Belvoir, VA: Defense Technical Information Center, July 2014. http://dx.doi.org/10.21236/ada609071.

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Usai, Jannet, Zita Ekeocha, Stephen Robert Byrn, and Kari L. Clase. Herbal Medicines Registration Process for Zimbabwe Overview of the Process. Purdue University, November 2021. http://dx.doi.org/10.5703/1288284317434.

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Unregistered traditional medicines pose a huge public health threat as the safety and efficacy of these products is unknown. The issue this study addresses is the inadequate regulatory measures for herbal medicines in Zimbabwe. This project was done to describe the current registration process of traditional medicines in Zimbabwe, and to identify the gaps and opportunities they present to improve the regulatory landscape. Regulations and laws governing the registration of herbal medicines in the country and published research on legislation of herbal medicines were reviewed. Two parallel regulatory bodies both registering and controlling the sale of herbal medicines were identified. The Medicines Control Authority of Zimbabwe (MCAZ) and the Traditional Medical Practitioners Association (TMPA) both derive their authority to regulate from the ministry of health and were established through the act of parliament which gives these authorities power to regulate the quality and sale of traditional medicines without giving a prescriptive way of doing it. The registration process, and product evaluations for the two authorities are different. While the MCAZ has a clearly defined registration process, the TMPA does not. However, MCAZ has not been very successful in registering local products with the majority of the registered herbal products being imports and only 2% of total registered products being local herbs. As a recommendation, there is need for collaboration between the regulatory bodies for consistence in quality of herbal products on the market and to improve registration of local herbal products. Developing monographs for local herbs commonly used in the country will also assist local manufacturer to fulfill the quality requirements and successful compilation of dossiers for product registration.
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Tidrow, M. Z. QWIP and MCT for Long Wavelength and Multicolor Focal Plane Array Applications,. Fort Belvoir, VA: Defense Technical Information Center, January 1997. http://dx.doi.org/10.21236/ada329057.

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Tidrow, Meimei Z. QWIP and MCT for Long Wavelength and Multicolor Focal Plane Array Applications. Fort Belvoir, VA: Defense Technical Information Center, May 1998. http://dx.doi.org/10.21236/ada345861.

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Smith, J., W. Brown, G. Roberson, H. Martz, and R. Klueg. Plan for the Purchase of MCT and EDS Reference Materials, Source Filters, Cu Strips, and Carousel Sub-Assemblies. Office of Scientific and Technical Information (OSTI), March 2014. http://dx.doi.org/10.2172/1129979.

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Atkinson, E. A. Regional mapping and qualitative petroleum resource assessment of the Magdalen Basin, Gulf of St. Lawrence, Quebec, Prince Edward Island, New Brunswick, Nova Scotia, and Newfoundland and Labrador. Natural Resources Canada/CMSS/Information Management, 2023. http://dx.doi.org/10.4095/331452.

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The Geological Survey of Canada conducted a broad regional study of the Magdalen Basin in the Gulf of St. Lawrence, as part of the Marine Conservation Targets initiative. MCT is a national initiative to protect more of Canada's offshore areas, and resource assessment and related regional mapping are part of the review process. This study assembled a large seismic and geologic database that allowed new regional mapping of several key horizons in this basin. Digital seismic data was donated by industry, and reprocessing undertaken both in-house and with contractors. Wells were correlated and tops from literature were used to indentify regional reflection packages. Regionally consistent two-way time interpretations add to confidence. Depth conversion used regional time-depth functions from literature, which were developed from refraction data, with a residual correction for the water column. Nine regional depth maps and eight isopach maps were produced, including Pre-Horton Basement, Horton Group Isopach, Base Windsor Group, Top Salt, Top Bradelle Formation, Bradelle / Cumberland Isopach, and Top Cable Head Formation. These maps illustrate that the Pre-Horton basement is about 15 km deep in the centre of the basin. Two main trends are visible in the Horton Grabens, which may relate to basin formation, and no significant reactivation of deeper Appalachian structure is observed. In the basin centre, the more robust Base Windsor Unconformity horizon reaches about 12 km deep, and a key reservoir and source sequence in the Bradelle Formation reaches 7 km. These maps are useful for considering regional stratigraphy. The new mapping also constrained basin models and became the input for our Qualitative Petroleum Potential map. Basin modelling reveals scenarios where oil may be preserved. The petroleum potential of the region is highest north of Îles de la Madeleine and southeast of Îles de la Madeleine and northwest of Cape Breton.
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