ALBERT

Description: Background: Worldwide preeclampsia (PE) is the leading cause of maternal death and affects 5 to 8% of pregnant women. PE is characterized by elevated blood pressure and proteinuria. Doppler Ultrasound (US) evaluation has been considered a useful method for prediction of PE; however, there is no complete data about the most frequently altered US parameters in the pathology. The aim of this study was to evaluate the uterine, umbilical, and the middle cerebral arteries using Doppler US parameters [resistance index (RI), pulsatility index (PI), notch (N), systolic peak (SP) and their combinations] in pregnant women, in order to make a global evaluation of hemodynamic repercussion caused by the established PE. Results: A total of 102 pregnant Mexican women (65 PE women and 37 normotensive women) were recruited in a cases and controls study. Blood velocity waveforms from uterine, umbilical, and middle cerebral arteries, in pregnancies from 24 to 37 weeks of gestation were recorded by trans-abdominal examination with a Toshiba Ultrasound Power Vision 6000 SSA-370A, with a 3.5 MHz convex transducer. Abnormal general Doppler US profile showed a positive association with PE [odds ratio (OR) = 2.93, 95% confidence interval (CI) = 1.2 - 7.3, P = 0.021)], and a specificity and predictive positive value of 89.2% and 88.6%, respectively. Other parameters like N presence, RI and PI of umbilical artery, as well as the PI of middle cerebral artery, showed differences between groups (P values 〈 0.05). Conclusion: General Doppler US result, as well as N from uterine vessel, RI from umbilical artery, and PI from umbilical and middle cerebral arteries in their individual form, may be considered as tools to determine hemodynamic repercussion caused by PE.

Description: Background: Worldwide preeclampsia (PE) is the leading cause of maternal death and affects 5 to 8% of pregnant women. PE is characterized by elevated blood pressure and proteinuria. Doppler Ultrasound (US) evaluation has been considered a useful method for prediction of PE; however, there is no complete data about the most frequently altered US parameters in the pathology. The aim of this study was to evaluate the uterine, umbilical, and the middle cerebral arteries using Doppler US parameters [resistance index (RI), pulsatility index (PI), notch (N), systolic peak (SP) and their combinations] in pregnant women, in order to make a global evaluation of hemodynamic repercussion caused by the established PE. Results: A total of 102 pregnant Mexican women (65 PE women and 37 normotensive women) were recruited in a cases and controls study. Blood velocity waveforms from uterine, umbilical, and middle cerebral arteries, in pregnancies from 24 to 37 weeks of gestation were recorded by trans-abdominal examination with a Toshiba Ultrasound Power Vision 6000 SSA-370A, with a 3.5 MHz convex transducer. Abnormal general Doppler US profile showed a positive association with PE [odds ratio (OR) = 2.93, 95% confidence interval (CI) = 1.2 - 7.3, P = 0.021)], and a specificity and predictive positive value of 89.2% and 88.6%, respectively. Other parameters like N presence, RI and PI of umbilical artery, as well as the PI of middle cerebral artery, showed differences between groups (P values 〈 0.05). Conclusion: General Doppler US result, as well as N from uterine vessel, RI from umbilical artery, and PI from umbilical and middle cerebral arteries in their individual form, may be considered as tools to determine hemodynamic repercussion caused by PE.

Description: Background Worldwide preeclampsia (PE) is the leading cause of maternal death and affects 5 to 8% of pregnant women. PE is characterized by elevated blood pressure and proteinuria. Doppler Ultrasound (US) evaluation has been considered a useful method for prediction of PE; however, there is no complete data about the most frequently altered US parameters in the pathology. The aim of this study was to evaluate the uterine, umbilical, and the middle cerebral arteries using Doppler US parameters [resistance index (RI), pulsatility index (PI), notch (N), systolic peak (SP) and their combinations] in pregnant women, in order to make a global evaluation of hemodynamic repercussion caused by the established PE. Results A total of 102 pregnant Mexican women (65 PE women and 37 normotensive women) were recruited in a cases and controls study. Blood velocity waveforms from uterine, umbilical, and middle cerebral arteries, in pregnancies from 24 to 37 weeks of gestation were recorded by trans-abdominal examination with a Toshiba Ultrasound Power Vision 6000 SSA-370A, with a 3.5 MHz convex transducer. Abnormal general Doppler US profile showed a positive association with PE [odds ratio (OR) = 2.93, 95% confidence interval (CI) = 1.2 - 7.3, P = 0.021)], and a specificity and predictive positive value of 89.2% and 88.6%, respectively. Other parameters like N presence, RI and PI of umbilical artery, as well as the PI of middle cerebral artery, showed differences between groups (P values 〈 0.05). Conclusion General Doppler US result, as well as N from uterine vessel, RI from umbilical artery, and PI from umbilical and middle cerebral arteries in their individual form, may be considered as tools to determine hemodynamic repercussion caused by PE.

Description: Background: The set of all mRNA molecules present in a cell constitute the transcriptome. The transcriptome varies depending on cell type as well as in response to internal and external stimuli during development. Here we present a study of the changes that occur in the transcriptome of chili pepper fruit during development and ripening. Results: RNA-Seq was used to obtain transcriptomes of whole Serrano-type chili pepper fruits (Capsicum annuum L.; 'Tampiqueño 74') collected at 10, 20, 40 and 60 days after anthesis (DAA). 15,550,468 Illumina MiSeq reads were assembled de novo into 34,066 chili genes. We classified the expression patterns of individual genes as well as genes grouped into Biological Process ontologies and Metabolic Pathway categories using statistical criteria. For the analyses of gene groups we added the weighted expression of individual genes. This method was effective in interpreting general patterns of expression changes and increased the statistical power of the analyses. We also estimated the variation in diversity and specialization of the transcriptome during chili pepper development. Approximately 17% of genes exhibited a significant change of expression in at least one of the intervals sampled. In contrast, significant differences in approximately 63% of the Biological Processes and 80% of the Metabolic Pathways studied were detected in at least one interval. Confirming previous reports, genes related to capsaicinoid and ascorbic acid biosynthesis were significantly upregulated at 20 DAA while those related to carotenoid biosynthesis were highly expressed in the last period of fruit maturation (40¿60 DAA). Our RNA-Seq data was validated by examining the expression of nine genes involved in carotenoid biosynthesis by qRT-PCR. Conclusions: In general, more profound changes in the chili fruit transcriptome were observed in the intervals between 10 to 20 and 40 to 60 DAA. The last interval, between 40 to 60 DAA, included 49% of all significant changes detected, and was characterized predominantly by a global decrease in gene expression. This period signals the end of maturation and the beginning of senescence of chili pepper fruit. The transcriptome at 60 DAA was the most specialized and least diverse of the four states sampled.

Description: Background: Multiple Sclerosis (MS) is an immune-mediated disease of the Central Nervous System with two major underlying etiopathogenic processes: inflammation and neurodegeneration. The latter determines the prognosis of this disease. MS is the main cause of non-traumatic disability in middle-aged populations.FindingsThe MS-VisualPath Cohort was set up to study the neurodegenerative component of MS using advanced imaging techniques by focusing on analysis of the visual pathway in a middle-aged MS population in Barcelona, Spain. We started the recruitment of patients in the early phase of MS in 2010 and it remains permanently open. All patients undergo a complete neurological and ophthalmological examination including measurements of physical and cognitive disability (Expanded Disability Status Scale; Multiple Sclerosis Functional Composite and neuropsychological tests), disease activity (relapses) and visual function testing (visual acuity, color vision and visual field). The MS-VisualPath protocol also assesses the presence of anxiety and depressive symptoms (Hospital Anxiety and Depression Scale), general quality of life (SF-36) and visual quality of life (25-Item National Eye Institute Visual Function Questionnaire with the 10-Item Neuro-Ophthalmic Supplement). In addition, the imaging protocol includes both retinal (Optical Coherence Tomography and Wide-Field Fundus Imaging) and brain imaging (Magnetic Resonance Imaging). Finally, multifocal Visual Evoked Potentials are used to perform neurophysiological assessment of the visual pathway.DiscussionThe analysis of the visual pathway with advance imaging and electrophysilogical tools in parallel with clinical information will provide significant and new knowledge regarding neurodegeneration in MS and provide new clinical and imaging biomarkers to help monitor disease progression in these patients.

Description: Background: It has been reported that the histone deacetylase inhibitor (iHDAc) trichostatin A (TSA) induces an increase in MDR1 gene transcription (ABCB1). This result would compromise the use of iHDACs in combination with other cytotoxic agents that are substrates of P-glycoprotein (Pgp). It has also been reported the use of alternative promoters by the ABCB1 gene and the existence of a traslational control of Pgp protein. Finally, the ABCB1 gene is located in a genetic locus with the nested gene RUNDC3B in the complementary DNA strand, raising the possibility that RUNDC3B expression could interfere with ABCB1 alternative promoter regulation. Methods: A combination of RT-PCR, real time RT-PCR, Western blot and drug accumulation assays by flow cytometry have been used in this study. Results: The iHDACs-induced increase in MDR1 mRNA levels is not followed by a subsequent increase in Pgp protein levels or activity in several pancreatic and colon carcinoma cell lines, suggesting a traslational control of Pgp in these cell lines. In addition, the MDR1 mRNA produced in these cell lines is shorter in its 5' end that the Pgp mRNA produced in cell lines expressing Pgp protein. The different size of the Pgp mRNA is due to the use of alternative promoters. We also demonstrate that these promoters are differentially regulated by TSA. The translational blockade of Pgp mRNA in the pancreatic carcinoma cell lines could be related to alterations in the 5' end of the MDR1 mRNA in the Pgp protein expressing cell lines. In addition, we demonstrate that the ABCB1 nested gene RUNDC3B expression although upregulated by TSA is independent of the ABCB1 alternative promoter used. Conclusions: The results show that the increase in MDR1 mRNA expression after iHDACs treatment is clinically irrelevant since this mRNA does not render an active Pgp protein, at least in colon and pancreatic cancer cell lines. Furthermore, we have demonstrated that TSA in fact, differentially regulates both ABCB1 promoters, downregulating the upstream promoter that is responsible for active P-glycoprotein expression. These results suggest that iHDACs such as TSA may in fact potentiate the effects of antitumoral drugs that are substrates of Pgp. Finally, we have also demonstrate that TSA upregulates RUNDC3B mRNA independently of the ABCB1 promoter in use.

Description: Stable isotope ratios of H, C, and O are powerful indicators of a wide variety of planetary geophysical processes, and for Mars they reveal the record of loss of its atmosphere and subsequent interactions with its surface such as carbonate formation. We report in situ measurements of the isotopic ratios of D/H and (18)O/(16)O in water and (13)C/(12)C, (18)O/(16)O, (17)O/(16)O, and (13)C(18)O/(12)C(16)O in carbon dioxide, made in the martian atmosphere at Gale Crater from the Curiosity rover using the Sample Analysis at Mars (SAM)'s tunable laser spectrometer (TLS). Comparison between our measurements in the modern atmosphere and those of martian meteorites such as ALH 84001 implies that the martian reservoirs of CO2 and H2O were largely established ~4 billion years ago, but that atmospheric loss or surface interaction may be still ongoing.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Webster, Chris R -- Mahaffy, Paul R -- Flesch, Gregory J -- Niles, Paul B -- Jones, John H -- Leshin, Laurie A -- Atreya, Sushil K -- Stern, Jennifer C -- Christensen, Lance E -- Owen, Tobias -- Franz, Heather -- Pepin, Robert O -- Steele, Andrew -- MSL Science Team -- Achilles, Cherie -- Agard, Christophe -- Alves Verdasca, Jose Alexandre -- Anderson, Robert -- Anderson, Ryan -- Archer, Doug -- Armiens-Aparicio, Carlos -- Arvidson, Ray -- Atlaskin, Evgeny -- Aubrey, Andrew -- Baker, Burt -- Baker, Michael -- Balic-Zunic, Tonci -- Baratoux, David -- Baroukh, Julien -- Barraclough, Bruce -- Bean, Keri -- Beegle, Luther -- Behar, Alberto -- Bell, James -- Bender, Steve -- Benna, Mehdi -- Bentz, Jennifer -- Berger, Gilles -- Berger, Jeff -- Berman, Daniel -- Bish, David -- Blake, David F -- Blanco Avalos, Juan J -- Blaney, Diana -- Blank, Jen -- Blau, Hannah -- Bleacher, Lora -- Boehm, Eckart -- Botta, Oliver -- Bottcher, Stephan -- Boucher, Thomas -- Bower, Hannah -- Boyd, Nick -- Boynton, Bill -- Breves, Elly -- Bridges, John -- Bridges, Nathan -- Brinckerhoff, William -- Brinza, David -- Bristow, Thomas -- Brunet, Claude -- Brunner, Anna -- Brunner, Will -- Buch, Arnaud -- Bullock, Mark -- Burmeister, Sonke -- Cabane, Michel -- Calef, Fred -- Cameron, James -- Campbell, John -- Cantor, Bruce -- Caplinger, Michael -- Caride Rodriguez, Javier -- Carmosino, Marco -- Carrasco Blazquez, Isaias -- Charpentier, Antoine -- Chipera, Steve -- Choi, David -- Clark, Benton -- Clegg, Sam -- Cleghorn, Timothy -- Cloutis, Ed -- Cody, George -- Coll, Patrice -- Conrad, Pamela -- Coscia, David -- Cousin, Agnes -- Cremers, David -- Crisp, Joy -- Cros, Alain -- Cucinotta, Frank -- d'Uston, Claude -- Davis, Scott -- Day, Mackenzie -- de la Torre Juarez, Manuel -- DeFlores, Lauren -- DeLapp, Dorothea -- DeMarines, Julia -- DesMarais, David -- Dietrich, William -- Dingler, Robert -- Donny, Christophe -- Downs, Bob -- Drake, Darrell -- Dromart, Gilles -- Dupont, Audrey -- Duston, Brian -- Dworkin, Jason -- Dyar, M Darby -- Edgar, Lauren -- Edgett, Kenneth -- Edwards, Christopher -- Edwards, Laurence -- Ehlmann, Bethany -- Ehresmann, Bent -- Eigenbrode, Jen -- Elliott, Beverley -- Elliott, Harvey -- Ewing, Ryan -- Fabre, Cecile -- Fairen, Alberto -- Farley, Ken -- Farmer, Jack -- Fassett, Caleb -- Favot, Laurent -- Fay, Donald -- Fedosov, Fedor -- Feldman, Jason -- Feldman, Sabrina -- Fisk, Marty -- Fitzgibbon, Mike -- Floyd, Melissa -- Fluckiger, Lorenzo -- Forni, Olivier -- Fraeman, Abby -- Francis, Raymond -- Francois, Pascaline -- Freissinet, Caroline -- French, Katherine Louise -- Frydenvang, Jens -- Gaboriaud, Alain -- Gailhanou, Marc -- Garvin, James -- Gasnault, Olivier -- Geffroy, Claude -- Gellert, Ralf -- Genzer, Maria -- Glavin, Daniel -- Godber, Austin -- Goesmann, Fred -- Goetz, Walter -- Golovin, Dmitry -- Gomez Gomez, Felipe -- Gomez-Elvira, Javier -- Gondet, Brigitte -- Gordon, Suzanne -- Gorevan, Stephen -- Grant, John -- Griffes, Jennifer -- Grinspoon, David -- Grotzinger, John -- Guillemot, Philippe -- Guo, Jingnan -- Gupta, Sanjeev -- Guzewich, Scott -- Haberle, Robert -- Halleaux, Douglas -- Hallet, Bernard -- Hamilton, Vicky -- Hardgrove, Craig -- Harker, David -- Harpold, Daniel -- Harri, Ari-Matti -- Harshman, Karl -- Hassler, Donald -- Haukka, Harri -- Hayes, Alex -- Herkenhoff, Ken -- Herrera, Paul -- Hettrich, Sebastian -- Heydari, Ezat -- Hipkin, Victoria -- Hoehler, Tori -- Hollingsworth, Jeff -- Hudgins, Judy -- Huntress, Wesley -- Hurowitz, Joel -- Hviid, Stubbe -- Iagnemma, Karl -- Indyk, Steve -- Israel, Guy -- Jackson, Ryan -- Jacob, Samantha -- Jakosky, Bruce -- Jensen, Elsa -- Jensen, Jaqueline Klovgaard -- Johnson, Jeffrey -- Johnson, Micah -- Johnstone, Steve -- Jones, Andrea -- Joseph, Jonathan -- Jun, Insoo -- Kah, Linda -- Kahanpaa, Henrik -- Kahre, Melinda -- Karpushkina, Natalya -- Kasprzak, Wayne -- Kauhanen, Janne -- Keely, Leslie -- Kemppinen, Osku -- Keymeulen, Didier -- Kim, Myung-Hee -- Kinch, Kjartan -- King, Penny -- Kirkland, Laurel -- Kocurek, Gary -- Koefoed, Asmus -- Kohler, Jan -- Kortmann, Onno -- Kozyrev, Alexander -- Krezoski, Jill -- Krysak, Daniel -- Kuzmin, Ruslan -- Lacour, Jean Luc -- Lafaille, Vivian -- Langevin, Yves -- Lanza, Nina -- Lasue, Jeremie -- Le Mouelic, Stephane -- Lee, Ella Mae -- Lee, Qiu-Mei -- Lees, David -- Lefavor, Matthew -- Lemmon, Mark -- Lepinette Malvitte, Alain -- Leveille, Richard -- Lewin-Carpintier, Eric -- Lewis, Kevin -- Li, Shuai -- Lipkaman, Leslie -- Little, Cynthia -- Litvak, Maxim -- Lorigny, Eric -- Lugmair, Guenter -- Lundberg, Angela -- Lyness, Eric -- Madsen, Morten -- Maki, Justin -- Malakhov, Alexey -- Malespin, Charles -- Malin, Michael -- Mangold, Nicolas -- Manhes, Gerard -- Manning, Heidi -- Marchand, Genevieve -- Marin Jimenez, Mercedes -- Martin Garcia, Cesar -- Martin, Dave -- Martin, Mildred -- Martinez-Frias, Jesus -- Martin-Soler, Javier -- Martin-Torres, F Javier -- Mauchien, Patrick -- Maurice, Sylvestre -- McAdam, Amy -- McCartney, Elaina -- McConnochie, Timothy -- McCullough, Emily -- McEwan, Ian -- McKay, Christopher -- McLennan, Scott -- McNair, Sean -- Melikechi, Noureddine -- Meslin, Pierre-Yves -- Meyer, Michael -- Mezzacappa, Alissa -- Miller, Hayden -- Miller, Kristen -- Milliken, Ralph -- Ming, Douglas -- Minitti, Michelle -- Mischna, Michael -- Mitrofanov, Igor -- Moersch, Jeff -- Mokrousov, Maxim -- Molina Jurado, Antonio -- Moores, John -- Mora-Sotomayor, Luis -- Morookian, John Michael -- Morris, Richard -- Morrison, Shaunna -- Mueller-Mellin, Reinhold -- Muller, Jan-Peter -- Munoz Caro, Guillermo -- Nachon, Marion -- Navarro Lopez, Sara -- Navarro-Gonzalez, Rafael -- Nealson, Kenneth -- Nefian, Ara -- Nelson, Tony -- Newcombe, Megan -- Newman, Claire -- Newsom, Horton -- Nikiforov, Sergey -- Nixon, Brian -- Noe Dobrea, Eldar -- Nolan, Thomas -- Oehler, Dorothy -- Ollila, Ann -- Olson, Timothy -- de Pablo Hernandez, Miguel Angel -- Paillet, Alexis -- Pallier, Etienne -- Palucis, Marisa -- Parker, Timothy -- Parot, Yann -- Patel, Kiran -- Paton, Mark -- Paulsen, Gale -- Pavlov, Alex -- Pavri, Betina -- Peinado-Gonzalez, Veronica -- Peret, Laurent -- Perez, Rene -- Perrett, Glynis -- Peterson, Joe -- Pilorget, Cedric -- Pinet, Patrick -- Pla-Garcia, Jorge -- Plante, Ianik -- Poitrasson, Franck -- Polkko, Jouni -- Popa, Radu -- Posiolova, Liliya -- Posner, Arik -- Pradler, Irina -- Prats, Benito -- Prokhorov, Vasily -- Purdy, Sharon Wilson -- Raaen, Eric -- Radziemski, Leon -- Rafkin, Scot -- Ramos, Miguel -- Rampe, Elizabeth -- Raulin, Francois -- Ravine, Michael -- Reitz, Gunther -- Renno, Nilton -- Rice, Melissa -- Richardson, Mark -- Robert, Francois -- Robertson, Kevin -- Rodriguez Manfredi, Jose Antonio -- Romeral-Planello, Julio J -- Rowland, Scott -- Rubin, David -- Saccoccio, Muriel -- Salamon, Andrew -- Sandoval, Jennifer -- Sanin, Anton -- Sans Fuentes, Sara Alejandra -- Saper, Lee -- Sarrazin, Philippe -- Sautter, Violaine -- Savijarvi, Hannu -- Schieber, Juergen -- Schmidt, Mariek -- Schmidt, Walter -- Scholes, Daniel -- Schoppers, Marcel -- Schroder, Susanne -- Schwenzer, Susanne -- Sebastian Martinez, Eduardo -- Sengstacken, Aaron -- Shterts, Ruslan -- Siebach, Kirsten -- Siili, Tero -- Simmonds, Jeff -- Sirven, Jean-Baptiste -- Slavney, Susie -- Sletten, Ronald -- Smith, Michael -- Sobron Sanchez, Pablo -- Spanovich, Nicole -- Spray, John -- Squyres, Steven -- Stack, Katie -- Stalport, Fabien -- Stein, Thomas -- Stewart, Noel -- Stipp, Susan Louise Svane -- Stoiber, Kevin -- Stolper, Ed -- Sucharski, Bob -- Sullivan, Rob -- Summons, Roger -- Sumner, Dawn -- Sun, Vivian -- Supulver, Kimberley -- Sutter, Brad -- Szopa, Cyril -- Tan, Florence -- Tate, Christopher -- Teinturier, Samuel -- ten Kate, Inge -- Thomas, Peter -- Thompson, Lucy -- Tokar, Robert -- Toplis, Mike -- Torres Redondo, Josefina -- Trainer, Melissa -- Treiman, Allan -- Tretyakov, Vladislav -- Urqui-O'Callaghan, Roser -- Van Beek, Jason -- Van Beek, Tessa -- VanBommel, Scott -- Vaniman, David -- Varenikov, Alexey -- Vasavada, Ashwin -- Vasconcelos, Paulo -- Vicenzi, Edward -- Vostrukhin, Andrey -- Voytek, Mary -- Wadhwa, Meenakshi -- Ward, Jennifer -- Weigle, Eddie -- Wellington, Danika -- Westall, Frances -- Wiens, Roger Craig -- Wilhelm, Mary Beth -- Williams, Amy -- Williams, Joshua -- Williams, Rebecca -- Williams, Richard B -- Wilson, Mike -- Wimmer-Schweingruber, Robert -- Wolff, Mike -- Wong, Mike -- Wray, James -- Wu, Megan -- Yana, Charles -- Yen, Albert -- Yingst, Aileen -- Zeitlin, Cary -- Zimdar, Robert -- Zorzano Mier, Maria-Paz -- New York, N.Y. -- Science. 2013 Jul 19;341(6143):260-3. doi: 10.1126/science.1237961.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109, USA. chris.r.webster@jpl.nasa.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23869013" target="_blank"〉PubMed〈/a〉

Description: The regioselectivity of deprotonation reactions between arene substrates and basic metalating agents is usually governed by the electronic and/or coordinative characteristics of a directing group attached to the benzene ring. Generally, the reaction takes place in the ortho position, adjacent to the substituent. Here, we introduce a protocol by which the metalating agent, a disodium-monomagnesium alkyl-amide, forms a template that extends regioselectivity to more distant arene sites. Depending on the nature of the directing group, ortho-meta' or meta-meta' dimetalation is observed, in the latter case breaking the dogma of ortho metalation. This concept is elaborated through the characterization of both organometallic intermediates and electrophilically quenched products.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Martinez-Martinez, Antonio J -- Kennedy, Alan R -- Mulvey, Robert E -- O'Hara, Charles T -- New York, N.Y. -- Science. 2014 Nov 14;346(6211):834-7. doi: 10.1126/science.1259662.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, UK. ; WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, UK. r.e.mulvey@strath.ac.uk charlie.ohara@strath.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25395533" target="_blank"〉PubMed〈/a〉

Description: Background: Multiple Sclerosis (MS) is considered a T-cell-mediated autoimmune disease with a prototypical oscillatory behavior, as evidenced by the presence of clinical relapses. Understanding the dynamics of immune cells governing the course of MS, therefore, has many implications for immunotherapy. Here, we used flow cytometry to analyze the time-dependent behavior of antigen-specific effector (Teff) and regulatory (Treg) T cells and microglia in mice model of MS, Experimental Autoimmune Encephalomyelitis (EAE), and compared the observations with a mathematical cross-regulation model of T-cell dynamics in autoimmune disease. Results: We found that Teff and Treg cells specific to myelin olygodendrocyte glycoprotein (MOG) developed coupled oscillatory dynamics with a 4- to 5-day period and decreasing amplitude that was always higher for the Teff populations, in agreement with the mathematical model. Microglia activation followed the oscillations of MOG-specific Teff cells in the secondary lymphoid organs, but they were activated before MOG-specific T-cell peaks in the CNS. Finally, we assessed the role of B-cell depletion induced by anti-CD20 therapy in the dynamics of T cells in an EAE model with more severe disease after therapy. We observed that B-cell depletion decreases Teff expansion, although its oscillatory behavior persists. However, the effect of B cell depletion was more significant in the Treg population within the CNS, which matched with activation of microglia and worsening of the disease. Mathematical modeling of T-cell cross-regulation after anti-CD20 therapy suggests that B-cell depletion may influence the dynamics of T cells by fine-tuning their activation. Conclusions: The oscillatory dynamics of T-cells have an intrinsic origin in the physiological regulation of the adaptive immune response, which influences both disease phenotype and response to immunotherapy.