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https://www.readbyqxmd.com/read/29453322/the-mtor-targets-4e-bp1-2-restrain-tumor-growth-and-promote-hypoxia-tolerance-in-pten-driven-prostate-cancer
#1
Mei Ding, Theodorus H van der Kwast, Ravi N Vellanki, Warren D Foltz, Trevor D McKee, Nahum Sonenberg, Pier Paolo Pandolfi, Marianne Koritzinsky, Bradly G Wouters
The mTOR signaling pathway is a central regulator of protein synthesis and cellular metabolism in response to the availability of energy, nutrients, oxygen, and growth factors. mTOR activation leads to phosphorylation of multiple downstream targets including the eukaryotic initiation factor 4E (eIF4E) binding proteins-1 and -2 (EIF4EBP1/4E-BP1 and EIF4EBP2/4E-BP2). These binding proteins inhibit protein synthesis, but are inactivated by mTOR to stimulate cell growth and metabolism. However, the role of these proteins in the context of aberrant activation of mTOR, which occurs frequently in cancers through loss of PTEN or mutational activation of the PI3K/AKT pathway, is unclear...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29452867/deep-inspiration-breath-hold-level-variability-and-deformation-in-locoregional-breast-irradiation
#2
Leigh Conroy, Sarah Quirk, Elizabeth Watt, Gillian Ecclestone, Jessica L Conway, Ivo A Olivotto, Tien Phan, Wendy L Smith
PURPOSE: The purpose of this study was to evaluate the dosimetric effect of breath hold level variability and deformation on breast, chest wall, internal mammary chain (IMC) nodes, and heart. METHODS AND MATERIALS: Left-sided post-lumpectomy (n = 12) and postmastectomy (n = 3) patients underwent deep inspiration breath hold (DIBH) and exhale breath hold (EBH) computed tomography (CT) scans. Forward-planned locoregional breast plans were created on the DIBH scan...
February 13, 2018: Practical Radiation Oncology
https://www.readbyqxmd.com/read/29452204/antiviral-therapy-in-hepatitis-b-virus-infected-children-with-immune-tolerant-characters-a-pilot-open-lable-randomized-study
#3
Shishu Zhu, Hongfei Zhang, Yi Dong, Limin Wang, Zhiqiang Xu, Weiwei Liu, Yu Gan, Hongmei Tang, Dawei Chen, Fuchuan Wang, Pan Zhao
BACKGROUND & AIM: Chronic infection with hepatitis B virus (HBV) in children possesses a serious health problem worldwide. It remains unresolved how children with immune-tolerant chronic hepatitis B should be treated, who were commonly characterized by HBeAg positivity, high viral load, normal or mildly elevated ALT and no or minimal inflammation in liver histology. This trial aims to study the benefits of antiviral therapy in children with these characters. METHODS: This is a pilot open-lable randomized controlled study...
February 13, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29451645/intragastric-balloons-in-high-risk-obese-patients-in-a-brazilian-center-initial-experience
#4
Alana Costa Borges, Paulo César Almeida, Stella M T Furlani, Marcelo DE Sousa Cury, Shantanu Gaur
OBJECTIVE: to assess the short-term efficacy, tolerance and complications in high-risk morbidly obese patients treated with an intragastric balloon as a bridge for surgery. METHODS: we conducted a post-hoc analysis study in a Brazilian teaching hospital from 2010 to 2014, with 23 adult patients with a BMI of 48kg/m2, who received a single intragastric air or liquid balloon. We defined efficacy as 10% excess weight loss, and complications, as adverse events consequent to the intragastric balloon diagnosed after the initial accommodative period...
2018: Revista do Colégio Brasileiro de Cirurgiões
https://www.readbyqxmd.com/read/29450389/unilateral-eales-disease-a-case-report
#5
Andreea Nicolcescu, Carmen Mocanu, Loredana Dinu, Andrei Olaru, Mara Ionete, Dima Alin Stefanescu
Introduction. Eales disease is an idiopathic peripheral vascular occlusive disease characterized by inflammation, ischemia, and retinal neovascularization and is hallmarked by recurrent vitreous hemorrhages and vision loss. Case report. We present a case of a 48-year-old female with recurrent floaters and decreased vision in her right eye. The onset of symptoms was in 2007 when a diagnose of retinal vasculitis was made. She had no accompanying systemic signs and symptoms and no history of ocular trauma or previous tuberculosis infection...
April 2017: Romanian Journal of Ophthalmology
https://www.readbyqxmd.com/read/29449933/a-simplified-characterization-of-s-adenosyl-l-methionine-consuming-enzymes-with-1-step-ez-mtase-a-universal-and-straightforward-coupled-assay-for-in-vitro-and-in-vivo-setting
#6
Emmanuel S Burgos, Ryan O Walters, Derek M Huffman, David Shechter
Methyltransferases use S -adenosyl-l-methionine (SAM) to deposit methyl marks. Many of these epigenetic 'writers' are associated with gene regulation. As cancer etiology is highly correlated with misregulated methylation patterns, methyltransferases are emerging therapeutic targets. Successful assignment of methyltransferases' roles within intricate biological networks relies on (1) the access to enzyme mechanistic insights and (2) the efficient screening of chemical probes against these targets. To characterize methyltransferases in vitro and in vivo , we report a highly-sensitive one-step deaminase-linked continuous assay where the S -adenosyl-l-homocysteine (SAH) enzyme-product is rapidly and quantitatively catabolized to S -inosyl-l-homocysteine (SIH)...
September 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29447335/condition-dependent-generation-of-aquaporin-4-antibodies-from-circulating-b-cells-in-neuromyelitis-optica
#7
Robert Wilson, Mateusz Makuch, Anne-Kathrin Kienzler, James Varley, Jennifer Taylor, Mark Woodhall, Jacqueline Palace, M Isabel Leite, Patrick Waters, Sarosh R Irani
Autoantibodies to aquaporin-4 (AQP4) are pathogenic in neuromyelitis optica spectrum disorder (NMOSD). However, it is not known which B cells are the major contributors to circulating AQP4 antibodies nor which conditions promote their generation. Our experiments showed CD19+CD27++CD38++ circulating ex vivo antibody-secreting cells did not produce AQP4 antibodies under several culture conditions. To question whether other cells in circulation were capable of AQP4 antibody production, B cells were differentiated into antibody-secreting cells in vitro...
February 13, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29447283/gp96-deficiency-affects-tlr4-functionality-and-impairs-erk-and-p38-phosphorylation
#8
Jesus Cosin-Roger, Marianne R Spalinger, Pedro A Ruiz, Claudia Stanzel, Anne Terhalle, Lutz Wolfram, Hassan Melhem, Kirstin Atrott, Silvia Lang, Isabelle Frey-Wagner, Michael Fried, Michael Scharl, Martin Hausmann, Gerhard Rogler
Gp96 is an endoplasmic reticulum chaperone for multiple protein substrates. Its lack in intestinal macrophages of Crohn's disease (CD) patients is correlated with loss of tolerance against the host gut flora. Gp96 has been stablished to be an essential chaperone for Toll-like receptors (TLRs). We studied the impact of gp96-knockdown on TLR-function in macrophages. TLR2 and TLR4 expression was only decreased but not abolished when gp96 was knocked-down in cell lines, whereas in a monocyte/macrophage specific knock-out mouse model (LysMCre) TLR4 was abolished, while TLR2 was still present...
2018: PloS One
https://www.readbyqxmd.com/read/29446968/aging-and-altruism-in-intertemporal-choice
#9
Erika P Sparrow, Julia Spaniol
In addition to making decisions about gains and losses that affect only ourselves, we often make decisions that affect others. Research on life span changes in motivation suggests that altruistic motives become stronger with age, but no prior research has examined how altruism affects tolerance for temporal delays. Experiment 1 used a realistic financial decision making task involving choices for gains, losses, and donations. Each decision required an intertemporal choice between a smaller-immediate and a larger-later option...
February 15, 2018: Psychology and Aging
https://www.readbyqxmd.com/read/29443436/fitness-costs-of-infection-with-serratia-symbiotica-are-associated-with-greater-susceptibility-to-insecticides-in-the-pea-aphid-acyrthosiphon-pisum
#10
Marisa Skaljac, Phillipp Kirfel, Jens Grotmann, Andreas Vilcinskas
BACKGROUND: Aphids are agricultural pests that damage crops by direct feeding and by vectoring important plant viruses. Bacterial symbionts can influence aphid biology, e.g. by providing essential nutrients or facilitating adaptations to biotic and abiotic stress. RESULTS: We investigated the pea aphid (Acyrthosiphon pisum Harris) and its commonly associated secondary bacterial symbiont Serratia symbiotica to study the effect of this symbiont on host fitness and susceptibility to the insecticides imidacloprid, chlorpyrifos methyl, methomyl, cyantraniliprole and spirotetramat...
February 14, 2018: Pest Management Science
https://www.readbyqxmd.com/read/29442292/topical-immunotherapy-of-alopecia-areata-a-large-retrospective-study
#11
Nicola Zerbinati, Cristina Esposito, Edoardo D'Este, Alberto Calligaro, Rossano Valsecchi
INTRODUCTION: Topical immunotherapy is frequently used in the treatment of alopecia areata (AA) although few studies report long-term follow-up. Our goals were to determine the efficacy and the prognostic factors of topical immunotherapy in a large cohort of patients with AA treated in the departments of Dermatology and Venereology of Bergamo, Como and Pavia, from 1978 to January 2016. METHODS: A total of 252 patients with AA were evaluated retrospectively. RESULTS: All our patients developed an allergic reaction to a 2% solution of dinitrochlorobenzene (DNCB) or squaric acid dibutylester (SADBE) or diphenylcyclopropenone (DPCP)...
February 13, 2018: Dermatology and Therapy
https://www.readbyqxmd.com/read/29440899/aptamer-drug-conjugate-targeted-delivery-of-doxorubicin-in-a-her3-aptamer-functionalized-liposomal-delivery-system-reduces-cardiotoxicity
#12
Xiao-Qian Dou, Hua Wang, Jing Zhang, Fang Wang, Gui-Li Xu, Cheng-Cheng Xu, Huan-Hua Xu, Shen-Si Xiang, Jie Fu, Hai-Feng Song
Introduction: The toxic side effects of doxorubicin (DOX) have limited its use in chemotherapy. Neither liposomal DOX nor pegylated liposomal DOX are able to completely resolve this issue. This is a proof-of-concept study testing aptamer-drug conjugate (ApDC) targeted delivery systems for chemotherapeutic drugs. Methods: Aptamer library targeting human epidermal growth factor receptor 3 (HER3) was screened and affinity was determined by enzyme-linked immunosorbent assay...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29440390/high-dietary-fat-and-sucrose-results-in-an-extensive-and-time-dependent-deterioration-in-health-of-multiple-physiological-systems-in-mice
#13
James G Burchfield, Melkam A Kebede, Christopher C Meoli, Jacqueline Stöckli, P Tess Whitworth, Amanda L Wright, Nolan J Hoffman, Annabel Y Minard, Xiuquan Ma, James R Krycer, Marin E Nelson, Shi-Xiong Tan, Belinda Yau, Kristen C Thomas, Natalie K Y Wee, Ee-Cheng Khor, Ronaldo F Enriquez, Bryce Vissel, Trevor J Biden, Paul A Baldock, Kyle L Hoehn, James Cantley, Gregory J Cooney, David E James, Daniel J Fazakerley
Obesity is associated with metabolic dysfunction, including insulin resistance and hyperinsulinemia, and with disorders such as cardiovascular disease, osteoporosis, and neurodegeneration. Typically, these pathologies are examined in discrete model systems and with limited temporal resolution, and whether these disorders co-occur is therefore unclear. To address this question, we examined multiple physiological systems in male C57BL/6J mice following prolonged exposure to a high-fat/high-sucrose diet (HFHSD)...
February 13, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29439289/switching-from-reference-adalimumab-to-sb5-adalimumab-biosimilar-in-patients-with-rheumatoid-arthritis-52-week-phase-3-randomized-study-results
#14
Michael E Weinblatt, Asta Baranauskaite, Eva Dokoupilova, Agnieszka Zielinska, Janusz Jaworski, Artur Racewicz, Margarita Pileckyte, Krystyna Jedrychowicz-Rosiak, Inyoung Baek, Jeehoon Ghil
OBJECTIVES: The 24-week equivalent efficacy and comparable safety results of SB5 and reference adalimumab (ADA) from the phase 3 randomized study in patients with moderate to severe rheumatoid arthritis (RA) have been reported previously. This transition study evaluated patients who switched from ADA to SB5 or continued on SB5 or ADA up to 52 weeks. METHODS: In this phase 3 study, patients were initially randomized 1:1 to receive SB5 or ADA (40 mg subcutaneously every other week)...
February 13, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29437989/galactoglycerolipid-lipase-pgd1-is-involved-in-thylakoid-membrane-remodeling-in-response-to-adverse-environmental-conditions-in-chlamydomonas
#15
Zhi-Yan Du, Ben Franklin Lucker, Krzysztof Zienkiewicz, Tarryn E Miller, Agnieszka Zienkiewicz, Barbara B Sears, David M Kramer, Christoph Benning
Photosynthesis occurs in the thylakoid membrane, where the predominant lipid is monogalactosyldiacylglycerol (MGDG). As environmental conditions change, photosynthetic membranes have to adjust. In this study, we used a loss-of-function Chlamydomonas reinhardtii mutant deficient in the MGDG-specific lipase PGD1 (PLASTID GALACTOGLYCEROLIPID DEGRADATION1) to investigate the link between MGDG turnover, chloroplast ultrastructure, and the production of reactive oxygen species (ROS) in response to different adverse environmental conditions...
February 5, 2018: Plant Cell
https://www.readbyqxmd.com/read/29437791/a-phase-i-study-of-cpi-613-in-combination-with-high-dose-cytarabine-and-mitoxantrone-for-relapsed-or-refractory-acute-myeloid-leukemia
#16
Timothy S Pardee, Rebecca G Anderson, Kristin M Pladna, Scott Isom, Lais P Ghiraldeli, Lance D Miller, Jeff A Chou, Guangxu Jin, Wei Zhang, Leslie R Ellis, Dmitriy Berenzon, Dianna S Howard, David Hurd, Megan Manuel, Sarah Dralle, Susan Lyerly, Bayard L Powell
PURPOSE: CPI-613, a lipoate analog that inhibits pyruvate dehydrogenase (PDH) and α-ketogluterate dehydrogenase (KGDH) has activity in patients with myeloid malignancies. This study explored the role of mitochondrial metabolism in chemotherapy response, determined the maximally tolerated dose, efficacy and safety of CPI-613 combined with high dose cytarabine and mitoxantrone in patients with relapsed or refractory acute myeloid leukemia. METHODS: The role of mitochondrial response to chemotherapy was assessed in cell lines and animal models...
February 6, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29435989/improved-potassium-nutrition-retrieves-phosphorus-induced-decrease-in-uptake-and-grain-zinc-concentration-of-wheat
#17
Asif Naeem, Muhammad Aslam, Asma Lodhi
BACKGROUND: The negative effect of soil applied phosphorus (P) on zinc (Zn) uptake by plants and concentration in food grains could be a possible reason of low dietary intake of Zn. Likewise its critical role in plant tolerance to other abiotic stresses, potassium (K) was thought to retrieve P induced decrease in grain Zn concentration of wheat. To test the above hypothesis, effect of K application (50 mg kg-1 soil) on Zn concentration in shoot/grains and its shoot-to-grain translocation was studied in wheat (Triticum aestivum L, cv Galaxy 2013) under low and optimal supply of both P (10 and 50 mg kg-1 ) and Zn (0 and 5 mg kg-1 )...
February 13, 2018: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/29434480/a-rare-presentation-of-neuromyelitis-optica-spectrum-disorders
#18
Navneet K Singh, Alexander J Sweidan, Sarah Strube, Ignacio Carrillo-Nunez
Neuromyelitis optica spectrum disorders (NMOSDs) are a set of demyelinating disorders that primarily target the optic nerves and the spinal cord. Previously thought to be a subset of multiple sclerosis (MS), now is recognized as a distinct entity. We present a 59-year-old female patient who was admitted for acute upper and lower extremity weakness. The patient had woken up from sleep with sudden onset of weakness. Patient was initially diagnosed with a right hemispheric stroke; however, magnetic resonance imaging of the cervical spine later performed showed abnormal enhancement from C2-C4, representing transverse myelitis...
2018: Clinical Medicine Insights. Case Reports
https://www.readbyqxmd.com/read/29434236/the-drought-tolerant-solanum-pennellii-regulates-leaf-water-loss-and-induces-genes-involved-in-amino-acid-and-ethylene-jasmonate-metabolism-under-dehydration
#19
Isabel Egea, Irene Albaladejo, Victoriano Meco, Belén Morales, Angel Sevilla, Maria C Bolarin, Francisco B Flores
Breeding for drought-tolerant crops is a pressing issue due to the increasing frequency and duration of droughts caused by climate change. Although important sources of variation for drought tolerance exist in wild relatives, the mechanisms and the key genes controlling tolerance in tomato are little known. The aim of this study is to determine the drought response of the tomato wild relative Solanum pennellii (Sp) compared with the cultivated tomato Solanum lycopersicum (Sl). The paper investigates the physiological and molecular responses in leaves of Sp and Sl plants without stress and moderate drought stress...
February 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29427576/clinical-and-safety-outcomes-of-long-term-azithromycin-therapy-in-severe-copd-beyond-the-first-year-of-treatment
#20
Xavier Pomares, Concepción Montón, Miriam Bullich, Oscar Cuevas, Joan Carles Oliva, Miguel Gallego, Eduard Monsó
RATIONALE: Exacerbations of COPD (ECOPD) are a major cause of mortality and morbidity. Continuous cyclic azithromycin (CC-A) reduces the exacerbation rate but it is unknown whether it remains effective and safe beyond the first year. METHODS: Retrospective analysis of severe COPD GOLD D patients with ≥ 4 moderate-severe ECOPD who received CC-A (500mgr three times/week) as add-on therapy. Patients treated over 24 months were considered long-term CC-A (LT-CC-A) users, and ECOPD, hospitalizations and length of hospital stays during the first, second and third years were compared with the previous 12 months...
February 7, 2018: Chest
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