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Wei Zhang, Ana Bojorquez-Gomez, Daniel Ortiz Velez, Guorong Xu, Kyle S Sanchez, John Paul Shen, Kevin Chen, Katherine Licon, Collin Melton, Katrina M Olson, Michael Ku Yu, Justin K Huang, Hannah Carter, Emma K Farley, Michael Snyder, Stephanie I Fraley, Jason F Kreisberg, Trey Ideker
Although cancer genomes are replete with noncoding mutations, the effects of these mutations remain poorly characterized. Here we perform an integrative analysis of 930 tumor whole genomes and matched transcriptomes, identifying a network of 193 noncoding loci in which mutations disrupt target gene expression. These 'somatic eQTLs' (expression quantitative trait loci) are frequently mutated in specific cancer tissues, and the majority can be validated in an independent cohort of 3,382 tumors. Among these, we find that the effects of noncoding mutations on DAAM1, MTG2 and HYI transcription are recapitulated in multiple cancer cell lines and that increasing DAAM1 expression leads to invasive cell migration...
April 2, 2018: Nature Genetics
M Hermassi, J Dosta, C Valderrama, E Licon, N Moreno, X Querol, N H Batis, J L Cortina
The use of low-cost inorganic sorbents as a new sustainable strategy to enhance the valorization of nutrients (N-P-K), from the urban water cycle (e.g., side streams from sewage sludge anaerobic digestion), in agriculture applications is presented. The simultaneous recovery and stabilization of ammonium and phosphate by using a mixture of two reactive sorbents (Na and K zeolites and magnesium oxide) was evaluated. The nutrients stabilization process, favoured at alkaline pH values, is carried out by a) the precipitation of phosphate ions with magnesium and/or ammonium ions and b) the sorption of ammonium by Na- and K-zeolites...
February 27, 2018: Science of the Total Environment
Lizbeth Díaz, Karen Covarrubias, Ángel Licón, Mixtli Astorga, Yaneth Moreno, José Alejandro Martínez
INTRODUCTION: Hybrids from species and subspecies of Mexican triatomines have shown outstanding biological and behavioral characteristics as compared with their parental groups. This could lead to an increasing risk of transmission of Trypanosoma cruzi to human and animal reservoir hosts. OBJECTIVE: To describe and compare biological parameters related to the life cycle of Triatoma recurva, Meccus phyllosomus phyllosomus and their laboratory hybrids and estimate their risk as transmitters of T...
March 29, 2017: Biomédica: Revista del Instituto Nacional de Salud
Luz Elena Palma-Cano, Emilio J Córdova, Lorena Orozco, Angélica Martínez-Hernández, Miguel Cid, Irene Leal-Berumen, Angel Licón-Trillo, Ruth Lechuga-Valles, Mauricio González-Ponce, Everardo González-Rodríguez, Verónica Moreno-Brito
The GSTT1 and GSTM1 genes are key molecules in cellular detoxification. Null variants in these genes are associated with increase susceptibility to developing different types of cancers. The aim of this study was to determine the prevalence of GSTT1 and GSTM1 null genotypes in Mestizo and Amerindian individuals from the Northwestern region of Mexico, and to compare them with those reported worldwide. GSTT1 and GSTM1 null variants were genotyped by multiplex PCR in 211 Mestizos and 211 Amerindian individuals...
October 2017: Genetics and Molecular Biology
Yamhilette Licon-Munoz, Vera Michel, Colleen A Fordyce, Karlett J Parra
The vacuolar ATPase (V-ATPase) proton pump sustains cellular pH homeostasis, and its inhibition triggers numerous stress responses. However, the cellular mechanisms involved remain largely elusive in cancer cells. We studied V-ATPase in the prostate cancer (PCa) cell line PC-3, which has characteristics of highly metastatic PCa. V-ATPase inhibitors impaired endo-lysosomal pH, vesicle trafficking, migration, and invasion. V-ATPase accrual in the Golgi and recycling endosomes suggests that traffic of internalized membrane vesicles back to the plasma membrane was particularly impaired...
November 15, 2017: Biology Open
Arnaud Fournel, Caroline Sezille, Carmen C Licon, Charlotte Sinding, Johannes Gerber, Camille Ferdenzi, Thomas Hummel, Moustafa Bensafi
Semantic description of odors is a cognitively demanding task. Learning to name smells is, however, possible with training. This study set out to examine how improvement in olfactory semantic knowledge following training reorganizes the neural representation of smells. First, 19 nonexpert volunteers were trained for 3 days; they were exposed (i) to odorants presented without verbal labels (perceptual learning) and (ii) to other odorants paired with lexicosemantic labels (associative learning). Second, the same participants were tested in a brain imaging study (fMRI) measuring hemodynamic responses to learned odors presented in both the perceptual and associative learning conditions...
September 12, 2017: Human Brain Mapping
Camille Ferdenzi, Carmen Licon, Moustafa Bensafi
No abstract text is available yet for this article.
June 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
Jose A Bazan, Abigail Norris Turner, Robert D Kirkcaldy, Adam C Retchless, Cecilia B Kretz, Elizabeth Briere, Yih-Ling Tzeng, David S Stephens, Courtney Maierhofer, Carlos Del Rio, A Jeanine Abrams, David L Trees, Melissa Ervin, Denisse B Licon, Karen S Fields, Mysheika Williams Roberts, Amanda Dennison, Xin Wang
Background: Neisseria meningitidis (Nm) is a Gram-negative diplococcus that normally colonizes the nasopharynx and rarely infects the urogenital tract. On Gram stain of urethral exudates, Nm can be misidentified as the more common sexually transmitted pathogen Neisseria gonorrhoeae. Methods: In response to a large increase in cases of Nm urethritis identified among men presenting for screening at a sexually transmitted disease clinic in Columbus, Ohio, we investigated the epidemiologic characteristics of men with Nm urethritis and the molecular and phylogenetic characteristics of their Nm isolates...
July 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
A Yaroshchuk, E E Licón, E K Zholkovskiy, M P Bondarenko, T Heldal
To have non-zero net flow in AC electroosmotic pumps, the electroosmosis (EO) has to be non-linear and asymmetric. This can be achieved due to ionic concentration polarization. This is known to occur close to micro-/nano-interfaces provided that the sizes of the nanopores are not too large compared to the Debye screening length. However, operation of the corresponding EO pumps can be quite sensitive to the solution concentration and, thus, unstable in practical applications. Concentration polarization of ion-exchange membranes is much more robust...
July 1, 2017: Faraday Discussions
John Paul Shen, Dongxin Zhao, Roman Sasik, Jens Luebeck, Amanda Birmingham, Ana Bojorquez-Gomez, Katherine Licon, Kristin Klepper, Daniel Pekin, Alex N Beckett, Kyle Salinas Sanchez, Alex Thomas, Chih-Chung Kuo, Dan Du, Assen Roguev, Nathan E Lewis, Aaron N Chang, Jason F Kreisberg, Nevan Krogan, Lei Qi, Trey Ideker, Prashant Mali
We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies...
June 2017: Nature Methods
I Sancho, E Licon, C Valderrama, N de Arespacochaga, S López-Palau, J L Cortina
The integration of up-concentration processes to increase the efficiency of primary sedimentation, as a solution to achieve energy neutral wastewater treatment plants, requires further post-treatment due to the missing ammonium removal stage. This study evaluated the use of zeolites as a post-treatment step, an alternative to the biological removal process. A natural granular clinoptilolite zeolite was evaluated as a sorbent media to remove low levels (up to 100mg-N/L) of ammonium from treated wastewater using batch and fixed bed columns...
April 15, 2017: Science of the Total Environment
Michael H Kramer, Jean-Claude Farré, Koyel Mitra, Michael Ku Yu, Keiichiro Ono, Barry Demchak, Katherine Licon, Mitchell Flagg, Rama Balakrishnan, J Michael Cherry, Suresh Subramani, Trey Ideker
We have developed a general progressive procedure, Active Interaction Mapping, to guide assembly of the hierarchy of functions encoding any biological system. Using this process, we assemble an ontology of functions comprising autophagy, a central recycling process implicated in numerous diseases. A first-generation model, built from existing gene networks in Saccharomyces, captures most known autophagy components in broad relation to vesicle transport, cell cycle, and stress response. Systematic analysis identifies synthetic-lethal interactions as most informative for further experiments; consequently, we saturate the model with 156,364 such measurements across autophagy-activating conditions...
February 16, 2017: Molecular Cell
A Licon, J Ford, D Defoor, R Crownover, Y Li, C Ha, T Eng, W Jones, N Papanikolaou, S Stathakis, P Mavroidis
PURPOSE: To create an IMRT treatment plan quantitative score using QUANTEC dose/volume parameters to assess plan quality. METHODS: 132 IMRT patient plans of various treatment sites were evaluated. The optimized plan's dose volume histogram (DVH) was exported to Velocity for evaluation. The proposed scoring was based on calculating the shortest distance from the QUANTEC objective to the DVH line of each organ. Each plan was normalized against the "perfect" plan where the organs at risk (OAR) received no dose and hence the distance between the QUANTEC objective and the DVH line was maximized...
June 2016: Medical Physics
Marie H Foss, Sovitj Pou, Patrick M Davidson, Jennifer L Dunaj, Rolf W Winter, Sovijja Pou, Meredith H Licon, Julia K Doh, Yuexin Li, Jane X Kelly, Rozalia A Dodean, Dennis R Koop, Michael K Riscoe, Georgiana E Purdy
New treatments for tuberculosis infection are critical to combat the emergence of multidrug- and extensively drug-resistant Mycobacterium tuberculosis (Mtb). We report the characterization of a diphenylether-modified adamantyl 1,2-diamine that we refer to as TBL-140, which has a minimal inhibitory concentration (MIC99) of 1.2 μg/mL. TBL-140 is effective against drug-resistant Mtb and nonreplicating bacteria. In addition, TBL-140 eliminates expansion of Mtb in cell culture infection assays at its MIC. To define the mechanism of action of this compound, we performed a spontaneous mutant screen and biochemical assays...
July 8, 2016: ACS Infectious Diseases
Rohith Srivas, John Paul Shen, Chih Cheng Yang, Su Ming Sun, Jianfeng Li, Andrew M Gross, James Jensen, Katherine Licon, Ana Bojorquez-Gomez, Kristin Klepper, Justin Huang, Daniel Pekin, Jia L Xu, Huwate Yeerna, Vignesh Sivaganesh, Leonie Kollenstart, Haico van Attikum, Pedro Aza-Blanc, Robert W Sobol, Trey Ideker
An emerging therapeutic strategy for cancer is to induce selective lethality in a tumor by exploiting interactions between its driving mutations and specific drug targets. Here we use a multi-species approach to develop a resource of synthetic lethal interactions relevant to cancer therapy. First, we screen in yeast ∼169,000 potential interactions among orthologs of human tumor suppressor genes (TSG) and genes encoding drug targets across multiple genotoxic environments. Guided by the strongest signal, we evaluate thousands of TSG-drug combinations in HeLa cells, resulting in networks of conserved synthetic lethal interactions...
August 4, 2016: Molecular Cell
Jose A Bazan, Amy S Peterson, Robert D Kirkcaldy, Elizabeth C Briere, Courtney Maierhofer, Abigail Norris Turner, Denisse B Licon, Nicole Parker, Amanda Dennison, Melissa Ervin, Laura Johnson, Barbara Weberman, Pamela Hackert, Xin Wang, Cecilia B Kretz, A Jeanine Abrams, David L Trees, Carlos Del Rio, David S Stephens, Yih-Ling Tzeng, Mary DiOrio, Mysheika Williams Roberts
Neisseria meningitidis (Nm) urogenital infections, although less common than infections caused by Neisseria gonorrhoeae (Ng), have been associated with urethritis, cervicitis, proctitis, and pelvic inflammatory disease. Nm can appear similar to Ng on Gram stain analysis (gram-negative intracellular diplococci) (1-5). Because Nm colonizes the nasopharynx, men who receive oral sex (fellatio) can acquire urethral Nm infections (1,3,5). This report describes an increase in Nm-associated urethritis in men attending sexual health clinics in Columbus, Ohio, and Oakland County, Michigan...
June 3, 2016: MMWR. Morbidity and Mortality Weekly Report
Andrew M Gross, Philipp A Jaeger, Jason F Kreisberg, Katherine Licon, Kristen L Jepsen, Mahdieh Khosroheidari, Brenda M Morsey, Susan Swindells, Hui Shen, Cherie T Ng, Ken Flagg, Daniel Chen, Kang Zhang, Howard S Fox, Trey Ideker
HIV-infected individuals are living longer on antiretroviral therapy, but many patients display signs that in some ways resemble premature aging. To investigate and quantify the impact of chronic HIV infection on aging, we report a global analysis of the whole-blood DNA methylomes of 137 HIV+ individuals under sustained therapy along with 44 matched HIV- individuals. First, we develop and validate epigenetic models of aging that are independent of blood cell composition. Using these models, we find that both chronic and recent HIV infection lead to an average aging advancement of 4...
April 21, 2016: Molecular Cell
Michael Ku Yu, Michael Kramer, Janusz Dutkowski, Rohith Srivas, Katherine Licon, Jason Kreisberg, Cherie T Ng, Nevan Krogan, Roded Sharan, Trey Ideker
Accurately translating genotype to phenotype requires accounting for the functional impact of genetic variation at many biological scales. Here we present a strategy for genotype-phenotype reasoning based on existing knowledge of cellular subsystems. These subsystems and their hierarchical organization are defined by the Gene Ontology or a complementary ontology inferred directly from previously published datasets. Guided by the ontology's hierarchical structure, we organize genotype data into an "ontotype," that is, a hierarchy of perturbations representing the effects of genetic variation at multiple cellular scales...
February 24, 2016: Cell Systems
Adriana Leticia Perales-Torres, Octelina Castillo-Ruíz, María Teresa Castañeda Licón, Sanjuana E Alemán-Castillo, Juan Miguel Jiménez Andrade
The purpose of this review is to analyze the biochemical progression of atherosclerotic plaque and its association with diet and diabetes. This study shows the scientific evidence of demonstrating that diabetic patients present high levels of fatty acids like palmitic acid and linoleic acid in their atheroma plaques in comparison with non-diabetic patients. This study also establishes how patients with diabetes mellitus have a higher prevalence of atherosclerotic heart diseases in the form of Coronary Thrombosis and have different anatomopathological appearance like higher necrotic core and thin fibrotic layer than the general population...
October 2016: Archivos de Cardiología de México
John Paul Shen, Rohith Srivas, Andrew Gross, Jianfeng Li, Eric J Jaehnig, Su Ming Sun, Ana Bojorquez-Gomez, Katherine Licon, Vignesh Sivaganesh, Jia L Xu, Kristin Klepper, Huwate Yeerna, Daniel Pekin, Chu Ping Qiu, Haico van Attikum, Robert W Sobol, Trey Ideker
Chemical inhibitors of the checkpoint kinases have shown promise in the treatment of cancer, yet their clinical utility may be limited by a lack of molecular biomarkers to identify specific patients most likely to respond to therapy. To this end, we screened 112 known tumor suppressor genes for synthetic lethal interactions with inhibitors of the CHEK1 and CHEK2 checkpoint kinases. We identified eight interactions, including the Replication Factor C (RFC)-related protein RAD17. Clonogenic assays in RAD17 knockdown cell lines identified a substantial shift in sensitivity to checkpoint kinase inhibition (3...
November 3, 2015: Oncotarget
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