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T cell metabolism

Po C Liu, Yi T Lee, Chun Y Wang, Ya-Tang Yang
We describe a low cost, configurable morbidostat for characterizing the evolutionary pathway of antibiotic resistance. The morbidostat is a bacterial culture device that continuously monitors bacterial growth and dynamically adjusts the drug concentration to constantly challenge the bacteria as they evolve to acquire drug resistance. The device features a working volume of ~10 ml and is fully automated and equipped with optical density measurement and micro-pumps for medium and drug delivery. To validate the platform, we measured the stepwise acquisition of trimethoprim resistance in Escherichia coli MG 1655, and integrated the device with a multiplexed microfluidic platform to investigate cell morphology and antibiotic susceptibility...
September 27, 2016: Journal of Visualized Experiments: JoVE
Víctor Resco de Dios, Arthur Gessler, Juan Pedro Ferrio, Josu G Alday, Michael Bahn, Jorge Del Castillo, Sébastien Devidal, Sonia García-Muñoz, Zachary Kayler, Damien Landais, Paula Martín-Gómez, Alexandru Milcu, Clément Piel, Karin Pirhofer-Walzl, Olivier Ravel, Serajis Salekin, David T Tissue, Mark G Tjoelker, Jordi Voltas, Jacques Roy
BACKGROUND: Molecular clocks drive oscillations in leaf photosynthesis, stomatal conductance, and other cell and leaf-level processes over ~24 h under controlled laboratory conditions. The influence of such circadian regulation over whole-canopy fluxes remains uncertain; diurnal CO2 and H2O vapor flux dynamics in the field are currently interpreted as resulting almost exclusively from direct physiological responses to variations in light, temperature and other environmental factors. We tested whether circadian regulation would affect plant and canopy gas exchange at the Montpellier European Ecotron...
October 20, 2016: GigaScience
D Bogdanou, M Penna-Martinez, N Filmann, T L Chung, Y Moran-Auth, J Wehrle, C Cappel, S Huenecke, E Herrmann, U Koehl, K Badenhoop
BACKGROUND: Type 1 diabetes mellitus (T1D) is mediated by autoaggressive T effector cells with an underlying regulatory T cell (Treg) defect. Vitamin D (VD) deficiency is highly prevalent in T1D which can aggravate immune dysfunction. High dose VD treatment may enhance Tregs and improve metabolism in T1D patients. METHODS: In a randomized, double-blind, placebo-controlled trial with cross-over design, patients received either for three months cholecalciferol 4000 IU/d, followed by three months placebo or the sequential alternative...
October 20, 2016: Diabetes/metabolism Research and Reviews
K Bilmin, T Kujawska, W Secomski, A Nowicki, P Grieb
Sonodynamic therapy (SDT) is a promising technique based on the ability of certain substances, called sonosensitizers, to sensitize cancer cells to non-thermal effects of low-energy ultrasound waves, allowing their destruction. Sonosensitization is thought to induce cell death by direct physical effects such as cavitation and acoustical streaming as well as by complementary chemical reactions generating oxygen free radicals. One of the promising sonosensitizers is 5-aminolevulinic acid (ALA) which upon selective uptake by cancer cells is metabolized and accumulated as protoporphyrin IX...
2016: Folia Neuropathologica
Justus Mahnke, Valéa Schumacher, Stefanie Ahrens, Nadja Käding, Lea Marie Feldhoff, Magdalena Huber, Jan Rupp, Friederike Raczkowski, Hans-Willi Mittrücker
The transcription factor Interferon Regulatory Factor 4 (IRF4) is essential for TH2 and TH17 cell formation and controls peripheral CD8(+) T cell differentiation. We used Listeria monocytogenes infection to characterize the function of IRF4 in TH1 responses. IRF4(-/-) mice generated only marginal numbers of listeria-specific TH1 cells. After transfer into infected mice, IRF4(-/-) CD4(+) T cells failed to differentiate into TH1 cells as indicated by reduced T-bet and IFN-γ expression, and showed limited proliferation...
October 20, 2016: Scientific Reports
Marissa B Guzzo, Hoa T Nguyen, Thanh H Pham, Monika Wyszczelska-Rokiel, Hieronim Jakubowski, Kerstin A Wolff, Sam Ogwang, Joseph L Timpona, Soumya Gogula, Michael R Jacobs, Markus Ruetz, Bernhard Kräutler, Donald W Jacobsen, Guo-Fang Zhang, Liem Nguyen
The methylfolate trap, a metabolic blockage associated with anemia, neural tube defects, Alzheimer's dementia, cardiovascular diseases, and cancer, was discovered in the 1960s, linking the metabolism of folate, vitamin B12, methionine and homocysteine. However, the existence or physiological significance of this phenomenon has been unknown in bacteria, which synthesize folate de novo. Here we identify the methylfolate trap as a novel determinant of the bacterial intrinsic death by sulfonamides, antibiotics that block de novo folate synthesis...
October 2016: PLoS Pathogens
J A Molad, D T Blumenthal, F Bokstein, M Findler, I Finkel, N M Bornstein, S Yust-Katz, E Auriel
Post-radiation leukoencephalopathy is characterized by cognitive impairment and white matter alternations on imaging. Cerebral small vessel disease (SVD) is one of several suggested etiologies. Cerebral microinfarction (CMI) is a recently described marker of SVD. We sought to examine the rate of CMI as a biomarker of ongoing ischemia among patients who underwent brain radiotherapy (RT). 110 patients treated with RT for primary or metastatic brain tumors were enrolled. A total of 685 brain MRI tests performed 1-108 months post-radiation were examined...
October 18, 2016: Journal of Neuro-oncology
Yusuke Endo, Koutaro Yokote, Toshinori Nakayama
Chronic inflammation associated with obesity plays a major role in the development of metabolic diseases, cancer, and autoimmune diseases. Among Th subsets, Th17 cells are involved in the pathogenesis of autoimmune disorders such as psoriasis, rheumatoid arthritis, inflammatory bowel disease, steroid-resistant asthma, and multiple sclerosis. Accumulating data suggest that reciprocal interactions between the metabolic systems and immune system play pivotal roles in the pathogenesis of obesity-associated diseases...
October 18, 2016: Cellular and Molecular Life Sciences: CMLS
Prashant Trikha, Robert L Plews, Andrew Stiff, Shalini Gautam, Vincent Hsu, David Abood, Robert Wesolowski, Ian Landi, Xiaokui Mo, John Phay, Ching-Shih Chen, John Byrd, Michael Caligiuri, Susheela Tridandapani, William Carson
Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of early myeloid cells that accumulate in the blood and tumors of patients with cancer. MDSC play a critical role during tumor evasion and promote immune suppression through variety of mechanisms, such as the generation of reactive oxygen and nitrogen species (ROS and RNS) and cytokines. AMPactivated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase that regulates energy homeostasis and metabolic stress. However, the role of AMPK in the regulation of MDSC function remains largely unexplored...
2016: Oncoimmunology
Piotr T Filipczak, Cynthia L Thomas, Wenshu Chen, Andrew Salzman, Jacob D McDonald, Yong Lin, Steven A Belinsky
Tuberous sclerosis complex (TSC) is a genetic multi-organ disorder characterized by the development of neoplastic lesions in kidney, lung, brain, heart and skin. It is caused by an inactivating mutation in tumor suppressor genes coding the TSC1/TSC2 complex, resulting in hyperactivation of mTOR- and Raf/MEK/MAPK-dependent signaling that stimulates tumor cell proliferation and metastasis. Despite its oncogenic effect, cells with TSC deficiency were more sensitive to oxidative stress and dependent on mitochondrial metabolism, providing a rationale for a new therapeutic approach...
October 18, 2016: Cancer Research
Anne-Segolene Cottereau, Sebastien Hapdey, Loic Chartier, Romain Modzelewski, Olivier Casasnovas, Emmanuel Itti, Herve Tilly, Pierre Vera, Michel A Meignan, Stéphanie Becker
: To compare in a large series of Peripheral T cell lymphoma (PTCL), as a model of diffuse disease, the prognostic value of baseline Total Metabolic Tumor Volume (TMTV) measured on FDG-PET/CT with adaptive thresholding methods to TMTV measured with a fixed 41% SUVmax threshold method. METHODS: 106 patients with PTCL, staged with a PET/CT were enrolled from 5 LYSA centers. In this series TMTV computed with the 41% SUVmax threshold is a strong predictor of outcome (Ann Oncol, 2016)...
October 6, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Beata Banaszewska, Joanna Wrotyńska-Barczyńska, Robert Z Spaczynski, Leszek Pawelczyk, Antoni J Duleba
CONTEXT: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age. Hyperandrogenism is the central feature of PCOS. Studies on isolated ovarian theca-interstitial cells suggest that resveratrol, a natural polyphenol, reduces androgen production. OBJECTIVE: This study was designed to evaluate endocrine and metabolic effects of resveratrol on PCOS. DESIGN AND SETTING: This was a randomized (1:1) double-blind, placebo-controlled trial that evaluated the effects of resveratrol over a period of 3 months in an academic hospital...
October 18, 2016: Journal of Clinical Endocrinology and Metabolism
Felix Krenzien, Markus Quante, Timm Heinbokel, Midas Seyda, Koichiro Minami, Hirohito Uehara, Hector Rodriguez Cetina Biefer, Jeroen M Schuitenmaker, Steven Gabardi, Katrin Splith, Moritz Schmelzle, Athena K Petrides, Haruhito Azuma, Johann Pratschke, Xian C Li, Abdallah ElKhal, Stefan G Tullius
Immunosuppression in elderly recipients has been underappreciated in clinical trials. Here, we assessed age-specific effects of the calcineurin inhibitor Tacrolimus (TAC) in a murine transplant model and assessed its clinical relevance on human T-cells. Old recipient mice exhibited prolonged skin graft survival when compared to young animals following TAC administration. More importantly, half of the TAC dose was sufficient in old mice to achieve comparable systemic trough levels. TAC administration was able to reduce pro-inflammatory IFN-γ cytokine production and promote IL-10 production in old CD4(+) T-cells...
October 18, 2016: American Journal of Transplantation
Jong-Chan Youn, Hee Tae Yu, Hyeon Chang Kim, Suk-Won Choi, Seong-Woo Han, Kyu-Hyung Ryu, Eui-Cheol Shin, Sungha Park
OBJECTIVE: Chronic kidney disease (CKD) is associated with increased arterial stiffness, which is a well-known predictor of future cardiovascular events. However, the underlying mechanism of arterial stiffening in CKD is not well known. Accelerated immune aging, characterized by expansion of immunosenescent T cell fraction might be involved in the pathogenesis of arterial stiffening in CKD. We aimed to evaluate the relationship between arterial stiffness and immunosenescent T cell (CD8CD57 or CD8CD28 T cell) fraction in patients with CKD...
September 2016: Journal of Hypertension
Myung-Shik Lee
Low-grade systemic inflammation in adipose tissues or liver, is an important etiologic factor in insulin resistance. LPS is an important element causing such metabolic inflammation, and intestinal flora is considered a major source of systemic LPS. We studied changes of intestinal microbiota associated with high-fat diet (HFD) that causes insulin resistance and metabolic stress. 16S rRNA gene sequencing showed that HFD significantly decreased the abundance of a mucin-degrading bacterium Akkermansia muciniphila compared to control diet...
September 2016: Journal of Hypertension
Masatsugu Horiuchi
Hypertensive patients have greater chances of such cardiovascular events as stroke, coronary heart disease, heart or renal failure, peripheral artery disease, and dementia. It is also well recognized that diabetes increases the cardiovascular risks in concert with hypertension. Therefore, main goals for an innovation of anti-hypertensive therapy would be to achieve further risk reduction by targeting the functional, metabolic, and structural alterations associated with hypertension. Professors Dzau and Braunwald et al proposed the concept of "the cardiovascular disease continuum" in 1991, and that hypertension may trigger the chain of events, leading to end-stage heart disease; however, this concept was quite new at that time, and there was some discussion whether "the cardiovascular disease continuum" is true or not...
September 2016: Journal of Hypertension
Nora T Oliver, Christine M Hartman, Jennifer R Kramer, Elizabeth Y Chiao
INTRODUCTION: Chronic HIV/hepatitis C virus (HCV) coinfection carries increased risk of cirrhosis, hepatocellular carcinoma, and death. Due to anti-inflammatory properties, 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA) inhibitors (statins) may be useful adjunctive therapy to reduce liver disease progression. METHODS: Clinical information was extracted from the Veterans Affairs HIV and HCV Clinical Case Registries (1999-2010). HIV-related variables included combination antiretroviral therapy era of diagnosis, CD4 cell count, and percentage time with undetectable HIV viral load...
October 23, 2016: AIDS
Lien M Dos Santos, Tatiane M da Silva, Juliana H Azambuja, Priscila T Ramos, Pathise S Oliveira, Elita F da Silveira, Nathalia S Pedra, Kennia Galdino, Carlus A T do Couto, Mayara S P Soares, Rejane G Tavares, Roselia M Spanevello, Francieli M Stefanello, Elizandra Braganhol
Methionine is an essential amino acid involved in critical metabolic process, and regulation of methionine flux through metabolism is important to supply this amino acid for cell needs. Elevation in plasma methionine commonly occurs due to mutations in methionine-metabolizing enzymes, such as methionine adenosyltransferase. Hypermethioninemic patients exhibit clinical manifestations, including neuronal and liver disorders involving inflammation and tissue injury, which pathophysiology is not completely established...
October 17, 2016: Molecular and Cellular Biochemistry
Ryan Dean Fortune, Raymond J Grill, Christine Beeton, Mark Tanner, Redwan Huq, David S Loose
Spinal cord injury (SCI) results in devastating changes to almost all aspects of a patient's life. In addition to a permanent loss of sensory and motor function, males will also frequently exhibit a profound loss of fertility through poorly understood mechanisms. We demonstrate that SCI causes measureable pathology in the testis both acutely (24 hours) and chronically, up to 1.5 years post injury, leading to loss in sperm motility and viability. SCI has been shown in humans and rats to induce leukocytospermia, with the presence of inflammatory cytokines, anti-sperm antibodies, and reactive oxygen species found within the ejaculate...
October 18, 2016: Journal of Neurotrauma
Roma Patel, Mitesh Dwivedi, Mohmmad Shoab Mansuri, Ansarullah, Naresh C Laddha, Ami Thakker, A V Ramachandran, Rasheedunnisa Begum
BACKGROUND: Neuropeptide Y (NPY) is known to play a role in the regulation of satiety, energy balance, body weight, and insulin release. Interleukin-1beta (IL1B) has been associated with loss of beta-cell mass in type-II diabetes (TIID). OBJECTIVES: The present study attempts to investigate the association of NPY exon2 +1128 T/C (Leu7Pro; rs16139), NPY promoter -399 T/C (rs16147) and IL1B -511 C/T (rs16944) polymorphisms with TIID and their correlation with plasma lipid levels, BMI, and IL1B transcript levels...
2016: PloS One
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