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https://www.readbyqxmd.com/read/28538737/lymphatic-endothelial-s1p-promotes-mitochondrial-function-and-survival-in-naive-t-cells
#1
Alejandra Mendoza, Victoria Fang, Cynthia Chen, Madhavika Serasinghe, Akanksha Verma, James Muller, V Sai Chaluvadi, Michael L Dustin, Timothy Hla, Olivier Elemento, Jerry E Chipuk, Susan R Schwab
Effective adaptive immune responses require a large repertoire of naive T cells that migrate throughout the body, rapidly identifying almost any foreign peptide. Because the production of T cells declines with age, naive T cells must be long-lived. However, it remains unclear how naive T cells survive for years while constantly travelling. The chemoattractant sphingosine 1-phosphate (S1P) guides T cell circulation among secondary lymphoid organs, including spleen, lymph nodes and Peyer's patches, where T cells search for antigens...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28538732/cps1-maintains-pyrimidine-pools-and-dna-synthesis-in-kras-lkb1-mutant-lung-cancer-cells
#2
Jiyeon Kim, Zeping Hu, Ling Cai, Kailong Li, Eunhee Choi, Brandon Faubert, Divya Bezwada, Jaime Rodriguez-Canales, Pamela Villalobos, Yu-Fen Lin, Min Ni, Kenneth E Huffman, Luc Girard, Lauren A Byers, Keziban Unsal-Kacmaz, Christopher G Peña, John V Heymach, Els Wauters, Johan Vansteenkiste, Diego H Castrillon, Benjamin P C Chen, Ignacio Wistuba, Diether Lambrechts, Jian Xu, John D Minna, Ralph J DeBerardinis
Metabolic reprogramming by oncogenic signals promotes cancer initiation and progression. The oncogene KRAS and tumour suppressor STK11, which encodes the kinase LKB1, regulate metabolism and are frequently mutated in non-small-cell lung cancer (NSCLC). Concurrent occurrence of oncogenic KRAS and loss of LKB1 (KL) in cells specifies aggressive oncological behaviour. Here we show that human KL cells and tumours share metabolomic signatures of perturbed nitrogen handling. KL cells express the urea cycle enzyme carbamoyl phosphate synthetase-1 (CPS1), which produces carbamoyl phosphate in the mitochondria from ammonia and bicarbonate, initiating nitrogen disposal...
May 24, 2017: Nature
https://www.readbyqxmd.com/read/28538690/dysregulation-of-mirna-expression-in-cancer-associated-fibroblasts-cafs-and-its-consequences-on-the-tumor-microenvironment
#3
REVIEW
Maren Schoepp, Anda Jana Ströse, Jörg Haier
The tumor microenvironment, including cancer-associated fibroblasts (CAF), has developed as an important target for understanding tumor progression, clinical prognosis and treatment responses of cancer. Cancer cells appear to transform normal fibroblasts (NF) into CAFs involving direct cell-cell communication and epigenetic regulations. This review summarizes the current understanding on miR involvement in cancer cell-tumor environment/stroma communication, transformation of NFs into CAFs, their involved targets and signaling pathways in these interactions; and clinical relevance of CAF-related miR expression profiles...
May 24, 2017: Cancers
https://www.readbyqxmd.com/read/28538669/the-peroxisome-mitochondria-connection-how-and-why
#4
REVIEW
Marc Fransen, Celien Lismont, Paul Walton
Over the past decades, peroxisomes have emerged as key regulators in overall cellular lipid and reactive oxygen species metabolism. In mammals, these organelles have also been recognized as important hubs in redox-, lipid-, inflammatory-, and innate immune-signaling networks. To exert these activities, peroxisomes must interact both functionally and physically with other cell organelles. This review provides a comprehensive look of what is currently known about the interconnectivity between peroxisomes and mitochondria within mammalian cells...
May 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28538658/seed-coating-increases-seed-moisture-uptake-and-restricts-embryonic-oxygen-availability-in-germinating-cereal-seeds
#5
Linda Gorim, Folkard Asch
Seed coating is a technology to improve germination and homogenize stand establishment. Although coating often results in lower germination rates, seeds that do germinate grow more vigorously and show strongly reduced respiratory losses during reserve mobilization. We hypothesize that the higher mobilization efficiency is due to a shift in the enzymatic cleavage of sucrose from invertase to sucrose synthase in the embryonic tissue caused by a reduced oxygen availability induced by oversaturation with water caused by the coating during early germination...
May 24, 2017: Biology
https://www.readbyqxmd.com/read/28538514/long-term-outcome-of-4-patients-with-transcobalamin-deficiency-caused-by-2-novel-tcn2-mutations
#6
Marwan Nashabat, Gustavo Maegawa, Peter H Nissen, Ebba Nexo, Hussain Al-Shamrani, Mohammed Al-Owain, Majid Alfadhel
Cobalamin (vitamin B12 [Cbl]) is an essential cofactor for many biochemical pathways. Transcobalamin (TC) is required to internalize Cbl into the cells through membrane receptor-mediated endocytosis. Cbl is then processed in the cytoplasm and mitochondria by complementation factors leading to its active metabolites; methylcobalamin and 5-deoxyadenosyl-cobalamin. Deficiency of TC results in an elevation in methylmalonic acid and homocysteine. Patients usually present with macrocytic anemia, pancytopenia, failure to thrive, gastrointestinal symptoms, and neurological dysfunction...
May 22, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28538431/immunotherapy-for-lung-cancer-targeting-the-pd-1-pathway
#7
Sam Vafadar
Lung cancer is the third most common cancer in the United States and the top cause of cancer-related mortality in men and women. Despite advances in chemotherapy, molecular therapies, and CT screening, overall survival remains dismal. Additional options and a new treatment paradigm are needed. This article focuses on immunotherapy, a promising new approach targeted at the PD-1 inhibition pathway.
June 2017: JAAPA: Official Journal of the American Academy of Physician Assistants
https://www.readbyqxmd.com/read/28538427/return-on-investment-of-advanced-practice-medical-degrees-nps-vs-pas
#8
Christopher K Craig, James H Holmes, Jeffery E Carter
As the United States faces a predicted physician shortage over the next 2 decades, physician assistants (PAs) and NPs are expected to fill the void. At the same time, because education is expensive, student loan and tuition increases have many potential applicants assessing differences in reimbursement and wondering about their return on investment (ROI). An analysis compared PA and NP salaries by incorporating national salary data, federal income tax, and student loans for a comparative analysis of each career pathway...
June 2017: JAAPA: Official Journal of the American Academy of Physician Assistants
https://www.readbyqxmd.com/read/28538367/identifying-mirna-mrna-regulation-network-of-chronic-pancreatitis-based-on-the-significant-functional-expression
#9
Dan Wang, Lei Xin, Jin-Huan Lin, Zhuan Liao, Jun-Tao Ji, Ting-Ting Du, Fei Jiang, Zhao-Shen Li, Liang-Hao Hu
BACKGROUND: The aim of this study was to explore the underlying molecular mechanism and potential molecular biomarkers of chronic pancreatitis (CP) and construct a miRNA-mRNA regulation network. METHODS: To explore the involvement of miRNAs in CP, we downloaded the miRNA and mRNA expression profiles of CP patients and healthy controls and identified the differentially expressed miRNAs and genes. Functional analysis was conducted and significant pathways were utilized...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28538214/profiling-and-bioinformatic-analysis-of-circular-rna-expression-regulated-by-c-myc
#10
Qiheng Gou, Ke Wu, Jian-Kang Zhou, Yuxin Xie, Lunxu Liu, Yong Peng
The c-Myc transcription factor is involved in cell proliferation, cell cycle and apoptosis by activating or repressing transcription of multiple genes. Circular RNAs (circRNAs) are widely expressed non-coding RNAs participating in the regulation of gene expression. Using a high-throughput microarray assay, we showed that Myc regulates the expression of certain circRNAs. A total of 309 up- and 252 down-regulated circRNAs were identified. Among them, randomly selected 8 circRNAs were confirmed by real-time PCR...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28538193/ethyl-pyruvate-protects-pc12-cells-from-oxygen-glucose-deprivation-a-potential-role-in-ischemic-cerebrovascular-disease
#11
Wenbo Li, Jiyu Lou, Liping Wei, Hongying Bai, Yaohui Zhang, Yuqing He
The protective potential of ethyl pyruvate (EP) on neuron has been investigated previously. This study was intended to investigate the effects of EP on the severity of oxygen-glucose deprivation (OGD)-induced injury in neural-like PC12 cells. PC12 cells were exposed to OGD condition with or without EP treatment. Then, cell viability, apoptosis, and the expressions of neurotrophic factors were detected. Further, Sprague-Dawley rats were intravenously administered with 5mg/kg EP for 14 days post-middle cerebral artery occlusion (MCAO)...
May 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28538182/targeting-metabolic-reprogramming-by-influenza-infection-for-therapeutic-intervention
#12
Heather S Smallwood, Susu Duan, Marie Morfouace, Svetlana Rezinciuc, Barry L Shulkin, Anang Shelat, Erika E Zink, Sandra Milasta, Resha Bajracharya, Ajayi J Oluwaseum, Martine F Roussel, Douglas R Green, Ljiljana Pasa-Tolic, Paul G Thomas
Influenza is a worldwide health and financial burden posing a significant risk to the immune-compromised, obese, diabetic, elderly, and pediatric populations. We identified increases in glucose metabolism in the lungs of pediatric patients infected with respiratory pathogens. Using quantitative mass spectrometry, we found metabolic changes occurring after influenza infection in primary human respiratory cells and validated infection-associated increases in c-Myc, glycolysis, and glutaminolysis. We confirmed these findings with a metabolic drug screen that identified the PI3K/mTOR inhibitor BEZ235 as a regulator of infectious virus production...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28538181/malate-and-aspartate-increase-l-arginine-and-nitric-oxide-and-attenuate-hypertension
#13
Entai Hou, Na Sun, Fuchang Zhang, Chenyang Zhao, Kristie Usa, Mingyu Liang, Zhongmin Tian
Fumarase catalyzes the interconversion of fumarate and L-malate in the tricarboxylic acid cycle. The Dahl salt-sensitive (SS) rat, a model of salt-sensitive hypertension, exhibits fumarase insufficiencies. To investigate the mechanism mediating the effect of fumarase-related metabolites on hypertension, we considered the pathway in which L-malate can be converted to oxaloacetate, aspartate, argininosuccinate, and L-arginine, the substrate of nitric oxide (NO) synthase. The levels of aspartate, citrulline, L-arginine, and NO were significantly decreased in the kidneys of SS rats compared to salt-insensitive consomic SS...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28538164/post-translational-regulation-of-plant-immunity
#14
REVIEW
John Withers, Xinnian Dong
Plants have evolved multi-layered molecular defense strategies to protect against pathogens. Plant immune signaling largely relies on post-translational modifications (PTMs) to induce rapid alterations of signaling pathways to achieve a response that is appropriate to the type of pathogen and infection pressure. In host cells, dynamic PTMs have emerged as powerful regulatory mechanisms that cells use to adjust their immune response. PTM is also a virulence strategy used by pathogens to subvert host immunity through the activities of effector proteins secreted into the host cell...
May 21, 2017: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/28538152/apoptotic-bax-at-oxidatively-stressed-mitochondrial-membranes-lipid-dynamics-and-permeabilization
#15
Artur Peter Günther Dingeldein, Šárka Pokorná, Martin Lidman, Tobias Sparrman, Radek Šachl, Martin Hof, Gerhard Gröbner
Mitochondria are crucial compartments of eukaryotic cells because they function as the cellular power plant and play a central role in the early stages of programmed cell death (apoptosis). To avoid undesired cell death, this apoptotic pathway is tightly regulated by members of the Bcl-2 protein family, which interact on the external surface of the mitochondria, i.e., the mitochondrial outer membrane (MOM), and modulate its permeability to apoptotic factors, controlling their release into the cytosol. A growing body of evidence suggests that the MOM lipids play active roles in this permeabilization process...
May 23, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28538093/toxic-byproduct-formation-during-electrochemical-treatment-of-latrine-wastewater
#16
Justin T Jasper, Yang Yang, Michael R Hoffmann
Electrochemical systems are an attractive option for onsite latrine wastewater treatment due to their high efficiency and small footprint. While concerns remain over formation of toxic byproducts during treatment, rigorous studies examining byproduct formation are lacking. Experiments treating authentic latrine wastewater over variable treatment times, current densities, chloride concentrations, and anode materials were conducted to characterize byproducts and identify conditions that minimize their formation...
May 24, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28538012/antiphospholipid-syndrome-an-update-for-clinicians-and-scientists
#17
Andrew P Vreede, Paula L Bockenstedt, Jason S Knight
PURPOSE OF REVIEW: Antiphospholipid syndrome (APS) is a leading acquired cause of thrombosis and pregnancy loss. Upon diagnosis (which is unlikely to be made until at least one morbid event has occurred), anticoagulant medications are typically prescribed in an attempt to prevent future events. This approach is not uniformly effective and does not prevent associated autoimmune and inflammatory complications. The goal of this review is to update clinicians and scientists on mechanistic and clinically relevant studies from the past 18 months, which have especially focused on inflammatory aspects of APS pathophysiology...
May 22, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28537989/obesity-is-independently-associated-with-increased-risk-of-hepatocellular-cancer-related-mortality-a-systematic-review-and-meta-analysis
#18
Arjun Gupta, Avash Das, Kaustav Majumder, Nivedita Arora, Helen G Mayo, Preet P Singh, Muhammad S Beg, Siddharth Singh
OBJECTIVE: Excess body weight is associated with increased risk of developing hepatocellular cancer (HCC), but its effect on HCC-related mortality remains unclear. We performed a systematic review and meta-analysis to assess the association between premorbid obesity and HCC-related mortality. MATERIALS AND METHODS: Through a systematic literature search-up to March 2016, we identified 9 observational studies (1,599,453 individuals, 5705 HCC-related deaths) reporting the association between premorbid body mass index (BMI), and HCC-related mortality...
May 23, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28537986/an-update-on-lupus-animal-models
#19
Wei Li, Anton A Titov, Laurence Morel
PURPOSE OF REVIEW: The complexity and heterogeneity of the clinical presentation in systemic lupus of erythematosus (SLE), combined to the inherent limitations of clinical research, have made it difficult to investigate the cause of this disease directly in patients. Various mouse models have been developed to dissect the cellular and genetic mechanisms of SLE, as well as to identify therapeutic targets and to screen treatments. The purpose of this review is to summarize the major spontaneous and induced mouse models of SLE and to provide an update on the major advances they have contributed to the field...
May 19, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28537931/the-network-of-dab2ip-mir-138-in-regulating-drug-resistance-of-renal-cell-carcinoma-associated-with-stem-like-phenotypes
#20
Eun-Jin Yun, Jiancheng Zhou, Chun-Jung Lin, Shan Xu, John Santoyo, Elizabeth Hernandez, Chih-Ho Lai, Ho Lin, Dalin He, Jer-Tsong Hsieh
Targeted therapy is a standard of care for metastatic renal cell carcinoma (RCC) but the response rate is not overwhelmed, which only prolongs a short survival of patients due to the onset of therapeutic resistance. Although the mechanisms are not fully understood, the presence of cancer initiating cells (CIC) may underlie the drug resistance. Nevertheless, identifying CIC phenotypes with its biomarkers in RCC appear to be diverse and controversial from many reports. In this study, we took a different approach to focus on the regulatory mechanism in RCC-CIC and unveil DAB2IP-mediated miR-138 expression that plays a critical role in modulating stem-like phenotypes in RCC via targeting the ABC transporter (ABCA13) as well as oncogenic histone methyltransferase EZH2 while down regulation of miR-138 gene expression in RCC is due to epigenetic gene silencing by DNA methyltransferase 1 (DNMT1)...
May 9, 2017: Oncotarget
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