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https://www.readbyqxmd.com/read/28328117/noonan-syndrome-ptpn11-mutations-and-brain-tumors-a-clinical-report-and-review-of-the-literature
#1
Aurore Siegfried, Claude Cances, Marie Denuelle, Najat Loukh, Maïté Tauber, Hélène Cavé, Marie-Bernadette Delisle
Noonan syndrome (NS), an autosomal dominant disorder, is characterized by short stature, congenital heart defects, developmental delay, and facial dysmorphism. PTPN11 mutations are the most common cause of NS. PTPN11 encodes a non-receptor protein tyrosine phosphatase, SHP2. Hematopoietic malignancies and solid tumors are associated with NS. Among solid tumors, brain tumors have been described in children and young adults but remain rather rare. We report a 16-year-old boy with PTPN11-related NS who, at the age of 12, was incidentally found to have a left temporal lobe brain tumor and a cystic lesion in the right thalamus...
April 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28303547/persistent-lymphopenia-is-a-risk-factor-for-icu-acquired-infections-and-for-death-in-icu-patients-with-sustained-hypotension-at-admission
#2
Christophe Adrie, Maxime Lugosi, Romain Sonneville, Bertrand Souweine, Stéphane Ruckly, Jean-Charles Cartier, Maité Garrouste-Orgeas, Carole Schwebel, Jean-François Timsit
BACKGROUND: Severely ill patients might develop an alteration of their immune system called post-aggressive immunosuppression. We sought to assess the risk of ICU-acquired infection and of mortality according to the absolute lymphocyte count at ICU admission and its changes over 3 days. METHODS: Adults in ICU for at least 3 days with a shock or persistent low blood pressure were extracted from a French ICU database and included. We evaluated the impact of the absolute lymphocyte count at baseline and its change at day 3 on the incidence of ICU-acquired infection and on the 28-day mortality rate...
December 2017: Annals of Intensive Care
https://www.readbyqxmd.com/read/28288675/activation-status-of-mucosal-associated-invariant-t-cells-reflects-disease-activity-and-pathology-of-systemic-lupus-erythematosus
#3
Asako Chiba, Naoto Tamura, Kazunori Yoshikiyo, Goh Murayama, Mie Kitagaichi, Ken Yamaji, Yoshinari Takasaki, Sachiko Miyake
BACKGROUND: Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes constituting a large proportion of peripheral blood T cells expressing αβ T-cell receptor in humans. In this study, we aimed to investigate their involvement in systemic lupus erythematosus (SLE). METHODS: Peripheral blood MAIT cells from patients with SLE were assessed for their frequency, activation markers, and cell death by flow cytometry. The correlation between plasma cytokine levels and CD69 expression on MAIT cells was analyzed...
March 14, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28272391/stabilizing-short-lived-schiff-base-derivatives-of-5-aminouracils-that-activate-mucosal-associated-invariant-t-cells
#4
Jeffrey Y W Mak, Weijun Xu, Robert C Reid, Alexandra J Corbett, Bronwyn S Meehan, Huimeng Wang, Zhenjun Chen, Jamie Rossjohn, James McCluskey, Ligong Liu, David P Fairlie
Mucosal-associated invariant T (MAIT) cells are activated by unstable antigens formed by reactions of 5-amino-6-D-ribitylaminouracil (a vitamin B2 biosynthetic intermediate) with glycolysis metabolites such as methylglyoxal. Here we show superior preparations of antigens in dimethylsulfoxide, avoiding their rapid decomposition in water (t1/2 1.5 h, 37 °C). Antigen solution structures, MAIT cell activation potencies (EC50 3-500 pM), and chemical stabilities are described. Computer analyses of antigen structures reveal stereochemical and energetic influences on MAIT cell activation, enabling design of a water stable synthetic antigen (EC50 2 nM)...
March 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28265374/erratum-mait-cells-new-guardians-of-the-liver
#5
Ayako Kurioka, Lucy J Walker, Paul Klenerman, Christian B Willberg
[This corrects the article DOI: 10.1038/cti.2016.51.].
February 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28249259/fibroblast-growth-factor-15-19-in-hepatocarcinogenesis
#6
Gloria Alvarez-Sola, Iker Uriarte, M Ujue Latasa, Raquel Urtasun, Marina Bárcena-Varela, Maria Elizalde, Maddalen Jiménez, Carlos M Rodriguez-Ortigosa, Fernando J Corrales, Maite G Fernández-Barrena, Carmen Berasain, Matías A Avila
BACKGROUND: Advanced hepatocellular carcinoma (HCC) is a neoplastic disease with a very bad prognosis and increasing worldwide incidence. HCCs are resistant to conventional chemotherapy and the multikinase inhibitor sorafenib is the only agent that has shown some clinical efficacy. It is therefore important to identify key molecular mechanisms driving hepatocarcinogenesis for the development of more efficacious therapies. However, HCCs are heterogeneous tumors and different molecular subclasses have been characterized...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28223441/rima-dependent-nuclear-accumulation-of-iyo-triggers-auxin-irreversible-cell-differentiation-in-arabidopsis
#7
Alfonso Muñoz, Silvina Mangano, Mary Paz González-García, Ramón Contreras, Michael B Sauer, Bert De Rybel, Dolf Weijers, José J Sánchez-Serrano, Maite Sanmartín, Enrique Rojo
The transcriptional regulator MINIYO (IYO) is essential and rate-limiting for initiating cell differentiation in Arabidopsis thaliana. Moreover, IYO moves from the cytosol into the nucleus in cells at the meristem periphery, possibly triggering their differentiation. However, the genetic mechanisms controlling IYO nuclear accumulation were unknown and the evidence that increased nuclear IYO levels trigger differentiation remained correlative. Searching for IYO interactors, we have identified RPAP2 IYO Mate (RIMA), a homologue of yeast and human proteins linked to nuclear import of selective cargo...
February 21, 2017: Plant Cell
https://www.readbyqxmd.com/read/28179539/smoking-reduces-circulating-cd26-hi-cd161-hi-mait-cells-in-healthy-individuals-and-patients-with-multiple-sclerosis
#8
Cecilie Ammitzbøll, Lars Börnsen, Jeppe Romme Christensen, Rikke Ratzer, Birgitte Romme Nielsen, Helle B Søndergaard, Marina R von Essen, Finn Sellebjerg
Upon chronic cigarette smoke exposure, inhaled antigens and irritants cause altered lung immune homeostasis. Circulating immune cells are affected, and smoking is associated with an increased risk of developing various disorders, including multiple sclerosis (MS). This study was conducted to determine the impact of smoking on circulating immune cell subsets. Furthermore, we determined whether any smoking-associated changes were related to MS. With the use of flow cytometry, CFSE assays, and ELISpot assays, we analyzed circulating immune cell phenotypes and quantified antigen-induced proliferation and cytokine secretion in smokers and nonsmokers in a cohort of 100 healthy individuals (HI)...
February 8, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28166248/characterization-of-three-dimensional-cancer-cell-migration-in-mixed-collagen-matrigel-scaffolds-using-microfluidics-and-image-analysis
#9
María Anguiano, Carlos Castilla, Martin Maška, Cristina Ederra, Rafael Peláez, Xabier Morales, Gorka Muñoz-Arrieta, Maite Mujika, Michal Kozubek, Arrate Muñoz-Barrutia, Ana Rouzaut, Sergio Arana, José Manuel Garcia-Aznar, Carlos Ortiz-de-Solorzano
Microfluidic devices are becoming mainstream tools to recapitulate in vitro the behavior of cells and tissues. In this study, we use microfluidic devices filled with hydrogels of mixed collagen-Matrigel composition to study the migration of lung cancer cells under different cancer invasion microenvironments. We present the design of the microfluidic device, characterize the hydrogels morphologically and mechanically and use quantitative image analysis to measure the migration of H1299 lung adenocarcinoma cancer cells in different experimental conditions...
2017: PloS One
https://www.readbyqxmd.com/read/28166217/drugs-and-drug-like-molecules-can-modulate-the-function-of-mucosal-associated-invariant-t-cells
#10
Andrew N Keller, Sidonia B G Eckle, Weijun Xu, Ligong Liu, Victoria A Hughes, Jeffrey Y W Mak, Bronwyn S Meehan, Troi Pediongco, Richard W Birkinshaw, Zhenjun Chen, Huimeng Wang, Criselle D'Souza, Lars Kjer-Nielsen, Nicholas A Gherardin, Dale I Godfrey, Lyudmila Kostenko, Alexandra J Corbett, Anthony W Purcell, David P Fairlie, James McCluskey, Jamie Rossjohn
The major-histocompatibility-complex-(MHC)-class-I-related molecule MR1 can present activating and non-activating vitamin-B-based ligands to mucosal-associated invariant T cells (MAIT cells). Whether MR1 binds other ligands is unknown. Here we identified a range of small organic molecules, drugs, drug metabolites and drug-like molecules, including salicylates and diclofenac, as MR1-binding ligands. Some of these ligands inhibited MAIT cells ex vivo and in vivo, while others, including diclofenac metabolites, were agonists...
April 2017: Nature Immunology
https://www.readbyqxmd.com/read/28164306/amustaline-s-303-treatment-inactivates-high-levels-of-zika-virus-in-red-blood-cell-components
#11
Andrew Laughhunn, Felicia Santa Maria, Julien Broult, Marion C Lanteri, Adonis Stassinopoulos, Didier Musso, Maite Aubry
BACKGROUND: The potential for Zika virus (ZIKV) transfusion-transmission (TT) has been demonstrated in French Polynesia and Brazil. Pathogen inactivation (PI) of blood products is a proactive strategy to inactivate TT pathogens including arboviruses. Inactivation of West Nile, dengue, Zika, and chikungunya viruses was previously demonstrated by photochemical treatment with amotosalen and ultraviolet A (UVA) illumination. In this study, we evaluated ZIKV inactivation in red blood cell (RBC) components by a chemical approach that uses amustaline (S-303) and glutathione (GSH)...
February 5, 2017: Transfusion
https://www.readbyqxmd.com/read/28158203/silymarin-suppresses-basal-and-stimulus-induced-activation-exhaustion-differentiation-and-inflammatory-markers-in-primary-human-immune-cells
#12
Erica S Lovelace, Nicholas J Maurice, Hannah W Miller, Chloe K Slichter, Robert Harrington, Amalia Magaret, Martin Prlic, Stephen De Rosa, Stephen J Polyak
Silymarin (SM), and its flavonolignan components, alter cellular metabolism and inhibit inflammatory status in human liver and T cell lines. In this study, we hypothesized that SM suppresses both acute and chronic immune activation (CIA), including in the context of HIV infection. SM treatment suppressed the expression of T cell activation and exhaustion markers on CD4+ and CD8+ T cells from chronically-infected, HIV-positive subjects. SM also showed a trend towards modifying CD4+ T cell memory subsets from HIV+ subjects...
2017: PloS One
https://www.readbyqxmd.com/read/28137756/endocytic-turnover-of-rab8-controls-cell-polarization
#13
Maite Vidal-Quadras, Mikkel R Holst, Monika K Francis, Elin Larsson, Mariam Hachimi, Wai Lok Yau, Johan Peränen, Fernando Martín-Belmonte, Richard Lundmark
Adaptation of cell shape and polarization through the formation and retraction of cellular protrusions requires balancing of endo- and exocytosis combined with fine-tuning of the local activity of small GTPases like Rab8. Here, we show that endocytic turnover of the plasma membrane at protrusions is directly coupled to surface removal and inactivation of Rab8. Removal is induced by reduced membrane tension and mediated by the GTPase regulator associated with focal adhesion kinase-1 (GRAF1), a regulator of clathrin independent endocytosis...
January 30, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28119353/fibroblast-growth-factor-15-19-fgf15-19-protects-from-diet-induced-hepatic-steatosis-development-of-an-fgf19-based-chimeric-molecule-to-promote-fatty-liver-regeneration
#14
Gloria Alvarez-Sola, Iker Uriarte, M Ujue Latasa, Maite G Fernandez-Barrena, Raquel Urtasun, Maria Elizalde, Marina Barcena-Varela, Maddalen Jiménez, Haisul C Chang, Roberto Barbero, Victoria Catalán, Amaia Rodríguez, Gema Frühbeck, José M Gallego-Escuredo, Aleix Gavaldà-Navarro, Francesc Villarroya, Carlos M Rodriguez-Ortigosa, Fernando J Corrales, Jesus Prieto, Pedro Berraondo, Carmen Berasain, Matias A Avila
OBJECTIVE: Fibroblast growth factor 15/19 (FGF15/19), an enterokine that regulates synthesis of hepatic bile acids (BA), has been proposed to influence fat metabolism. Without FGF15/19, mouse liver regeneration after partial hepatectomy (PH) is severely impaired. We studied the role of FGF15/19 in response to a high fat diet (HFD) and its regulation by saturated fatty acids. We developed a fusion molecule encompassing FGF19 and apolipoprotein A-I, termed Fibapo, and evaluated its pharmacological properties in fatty liver regeneration...
January 24, 2017: Gut
https://www.readbyqxmd.com/read/28119072/invariant-natural-killer-t-cells-and-mucosal-associated-invariant-t-cells-in-multiple-sclerosis
#15
REVIEW
Elena Bianchini, Sara De Biasi, Anna Maria Simone, Diana Ferraro, Patrizia Sola, Andrea Cossarizza, Marcello Pinti
Multiple sclerosis (MS) is a chronic progressive inflammatory demyelinating disorder of the central nervous system, and in several countries is a leading cause of permanent neurological disability in young adults, particularly women. MS is considered an autoimmune disease, caused by an aberrant immune response to environmental triggers in genetically susceptible subjects. However, the contribution of the innate or of the adaptive immune system to the development and progression of the disease has not yet been fully elucidated...
March 2017: Immunology Letters
https://www.readbyqxmd.com/read/28089359/transient-and-long-time-kinetic-responses-of-the-cadaveric-leg-during-internal-and-external-foot-rotation
#16
Alexander R Mait, Adwait Mane, Jason L Forman, John Paul Donlon, Bingbing Nie, Richard W Kent
The purpose of this study was to determine the long-time and transient characteristics of the moment generated by external (ER) and internal (IR) rotation of the calcaneus with respect to the tibia. Two human cadaver legs were disarticulated at the knee joint while maintaining the connective tissue between the tibia and fibula. An axial rotation of 21° was applied to the proximal tibia to generate either ER or IR while the fibula was unconstrained and the calcaneus was permitted to translate in the transverse plane...
February 28, 2017: Journal of Biomechanics
https://www.readbyqxmd.com/read/28089353/cerebrospinal-fluid-mitochondrial-dna-in-the-alzheimer-s-disease-continuum
#17
Laura Cervera-Carles, Daniel Alcolea, Ainara Estanga, Mirian Ecay-Torres, Andrea Izagirre, Montserrat Clerigué, Maite García-Sebastián, Jorge Villanúa, Clàudia Escalas, Rafael Blesa, Pablo Martínez-Lage, Alberto Lleó, Juan Fortea, Jordi Clarimón
Low levels of cell-free mitochondrial DNA (mtDNA) in the cerebrospinal fluid (CSF) of Alzheimer's disease (AD) patients have been identified and proposed as a novel biomarker for the disease. The lack of validation studies of previous results prompted us to replicate this finding in a comprehensive series of patients and controls. We applied droplet digital polymerase chain reaction in CSF specimens from 124 patients representing the AD spectrum and 140 neurologically healthy controls. The following preanalytical and analytical parameters were evaluated: the effect of freeze-thaw cycles on mtDNA, the linearity of mtDNA load across serial dilutions, and the mtDNA levels in the diagnostic groups...
December 22, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28069799/ikbke-is-required-during-kras-induced-pancreatic-tumorigenesis
#18
Mihir Rajurkar, Kyvan Dang, Maite G Fernandez-Barrena, Xiangfan Liu, Martin E Fernandez-Zapico, Brian C Lewis, Junhao Mao
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies lacking effective therapeutic strategies. Here, we show that the noncanonical IκB-related kinase, IKBKE, is a critical oncogenic effector during KRAS-induced pancreatic transformation. Loss of IKBKE inhibits the initiation and progression of pancreatic tumors in mice carrying pancreatic-specific KRAS activation. Mechanistically, we demonstrate that this protumoral effect of IKBKE involves the activation of GLI1 and AKT signaling and is independent of the levels of activity of the NF-κB pathway...
January 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28062719/characteristics-in-limbic-encephalitis-with-anti-adenylate-kinase-5-autoantibodies
#19
Le-Duy Do, Eve Chanson, Virginie Desestret, Bastien Joubert, François Ducray, Sabine Brugière, Yohann Couté, Maité Formaglio, Veronique Rogemond, Catherine Thomas-Antérion, Laura Borrega, Brice Laurens, Francois Tison, Jonathan Curot, Thomas De Brouker, Christine Lebrun-Frenay, Jean-Yves Delattre, Jean-Christophe Antoine, Jerome Honnorat
OBJECTIVE: To report 10 patients with limbic encephalitis (LE) and adenylate kinase 5 autoantibodies (AK5-Abs). METHODS: We conducted a retrospective study in a cohort of 50 patients with LE with uncharacterized autoantibodies and identified a specific target using immunohistochemistry, Western blotting, immunoprecipitation, mass spectrometry, and cell-based assay. RESULTS: AK5 (a known autoantigen of LE) was identified as the target of antibodies in the CSFs and sera of 10 patients with LE (median age 64 years; range 57-80), which was characterized by subacute anterograde amnesia without seizure and sometimes preceded by a prodromal phase of asthenia or mood disturbances...
February 7, 2017: Neurology
https://www.readbyqxmd.com/read/28049488/intracellular-trafficking-and-cellular-uptake-mechanism-of-phbv-nanoparticles-for-targeted-delivery-in-epithelial-cell-lines
#20
Juan P Peñaloza, Valeria Márquez-Miranda, Mauricio Cabaña-Brunod, Rodrigo Reyes-Ramírez, Felipe M Llancalahuen, Cristian Vilos, Fernanda Maldonado-Biermann, Luis A Velásquez, Juan A Fuentes, Fernando D González-Nilo, Maité Rodríguez-Díaz, Carolina Otero
BACKGROUND: Nanotechnology is a science that involves imaging, measurement, modeling and a manipulation of matter at the nanometric scale. One application of this technology is drug delivery systems based on nanoparticles obtained from natural or synthetic sources. An example of these systems is synthetized from poly(3-hydroxybutyrate-co-3-hydroxyvalerate), which is a biodegradable, biocompatible and a low production cost polymer. The aim of this work was to investigate the uptake mechanism of PHBV nanoparticles in two different epithelial cell lines (HeLa and SKOV-3)...
January 3, 2017: Journal of Nanobiotechnology
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