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https://www.readbyqxmd.com/read/29029388/rapamycin-induced-mir-21-promotes-mitochondrial-homeostasis-and-adaptation-in-mtorc1-activated-cells
#1
Hilaire C Lam, Heng-Jia Liu, Christian V Baglini, Harilaos Filippakis, Nicola Alesi, Julie Nijmeh, Heng Du, Alicia Llorente Lope, Katherine A Cottrill, Adam Handen, John M Asara, David J Kwiatkowski, Issam Ben-Sahra, William M Oldham, Stephen Y Chan, Elizabeth P Henske
mTORC1 hyperactivation drives the multi-organ hamartomatous disease tuberous sclerosis complex (TSC). Rapamycin inhibits mTORC1, inducing partial tumor responses; however, the tumors regrow following treatment cessation. We discovered that the oncogenic miRNA, miR-21, is increased in Tsc2-deficient cells and, surprisingly, further increased by rapamycin. To determine the impact of miR-21 in TSC, we inhibited miR-21 in vitro. miR-21 inhibition significantly repressed the tumorigenic potential of Tsc2-deficient cells and increased apoptosis sensitivity...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29028633/acute-kidney-injury-in-congenital-heart-disease
#2
Katja M Gist, David M Kwiatkowski, David S Cooper
PURPOSE OF REVIEW: Acute kidney injury (AKI) is associated with significant morbidity and mortality in patients with congenital heart disease undergoing cardiac surgery or in pediatric patients with congestive heart failure. RECENT FINDINGS: This review describes the definition and various manifestations of AKI, the impact of biomarkers on the diagnosis of AKI, the importance of fluid overload as a consequence of AKI and its long-term impact. SUMMARY: There are novel biomarkers for AKI detection that should facilitate early recognition and intervention to prevent or attenuate the effects of AKI and fluid overload...
October 11, 2017: Current Opinion in Cardiology
https://www.readbyqxmd.com/read/29028261/panoptes-web-based-exploration-of-large-scale-genome-variation-data
#3
Paul Vauterin, Ben Jeffery, Alistair Miles, Roberto Amato, Lee Hart, Ian Wright, Dominic Kwiatkowski
Motivation: The size and complexity of modern large-scale genome variation studies demand novel approaches for exploring and sharing the data. In order to unlock the potential of these data for a broad audience of scientists with various areas of expertise, a unified exploration framework is required that is accessible, coherent and user-friendly. Results: Panoptes is an open-source software framework for collaborative visual exploration of large-scale genome variation data and associated metadata in a web browser...
October 15, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29020632/activation-of-the-p53-transcriptional-program-sensitizes-cancer-cells-to-cdk7-inhibitors
#4
Sampada Kalan, Ramon Amat, Miriam Merzel Schachter, Nicholas Kwiatkowski, Brian J Abraham, Yanke Liang, Tinghu Zhang, Calla M Olson, Stéphane Larochelle, Richard A Young, Nathanael S Gray, Robert P Fisher
Cdk7, the CDK-activating kinase and transcription factor IIH component, is a target of inhibitors that kill cancer cells by exploiting tumor-specific transcriptional dependencies. However, whereas selective inhibition of analog-sensitive (AS) Cdk7 in colon cancer-derived cells arrests division and disrupts transcription, it does not by itself trigger apoptosis efficiently. Here, we show that p53 activation by 5-fluorouracil or nutlin-3 synergizes with a reversible Cdk7(as) inhibitor to induce cell death. Synthetic lethality was recapitulated with covalent inhibitors of wild-type Cdk7, THZ1, or the more selective YKL-1-116...
October 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28988769/comprehensive-molecular-characterization-of-muscle-invasive-bladder-cancer
#5
A Gordon Robertson, Jaegil Kim, Hikmat Al-Ahmadie, Joaquim Bellmunt, Guangwu Guo, Andrew D Cherniack, Toshinori Hinoue, Peter W Laird, Katherine A Hoadley, Rehan Akbani, Mauro A A Castro, Ewan A Gibb, Rupa S Kanchi, Dmitry A Gordenin, Sachet A Shukla, Francisco Sanchez-Vega, Donna E Hansel, Bogdan A Czerniak, Victor E Reuter, Xiaoping Su, Benilton de Sa Carvalho, Vinicius S Chagas, Karen L Mungall, Sara Sadeghi, Chandra Sekhar Pedamallu, Yiling Lu, Leszek J Klimczak, Jiexin Zhang, Caleb Choo, Akinyemi I Ojesina, Susan Bullman, Kristen M Leraas, Tara M Lichtenberg, Catherine J Wu, Nicholaus Schultz, Gad Getz, Matthew Meyerson, Gordon B Mills, David J McConkey, John N Weinstein, David J Kwiatkowski, Seth P Lerner
We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival "neuronal" subtype in which the majority of tumors lacked small cell or neuroendocrine histology...
October 4, 2017: Cell
https://www.readbyqxmd.com/read/28987056/the-role-of-the-cerebellum-in-the-regulation-of-language-functions
#6
REVIEW
Anna Starowicz-Filip, Adrian Andrzej Chrobak, Marek Moskała, Roger M Krzyżewski, Borys Kwinta, Stanisław Kwiatkowski, Olga Milczarek, Anna Rajtar-Zembaty, Dorota Przewoźnik
The present paper is a review of studies on the role of the cerebellum in the regulation of language functions. This brain structure until recently associated chiefly with motor skills, visual-motor coordination and balance, proves to be significant also for cognitive functioning. With regard to language functions, studies show that the cerebellum determines verbal fluency (both semantic and formal) expressive and receptive grammar processing, the ability to identify and correct language mistakes, and writing skills...
August 29, 2017: Psychiatria Polska
https://www.readbyqxmd.com/read/28971208/burden-of-aquagenic-pruritus-in-polycythaemia-vera
#7
Edyta Lelonek, Łukasz Matusiak, Tomasz Wróbel, Jacek Kwiatkowski, Jacek C Szepietowski
Aquagenic pruritus (AP) has a significant influence on quality of life (QoL) in patients with polycythaemia vera. This study analysed the impact of AP on patient well-being in 102 patients with polycythaemia vera. Intensity of pruritus was evaluated using a visual analogue scale (VAS), verbal rating scale (VRS) and a 4-item Itch Questionnaire. Psychosocial aspects of AP were assessed with the Hospital Anxiety and Depression Scale (HADS), EQ-5D and itch-specific QoL questionnaire (ItchyQoL). AP of mean duration 6...
October 3, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28950153/cognitive-outcomes-in-prenatal-methamphetamine-exposed-children-aged-six-to-seven-years
#8
Maja A Kwiatkowski, Kirsten A Donald, Dan J Stein, Jonathan Ipser, Kevin G F Thomas, Annerine Roos
BACKGROUND: Methamphetamine use among pregnant women has become a significant problem. Research delineating the cognitive outcomes of prenatal methamphetamine exposure (PME) in early childhood is limited, however. The aim of this study was to examine effects of PME on cognition in six-to-seven-year-old children. METHODS: PME children (n=23) and unexposed controls (n=22) completed a battery of neurocognitive tests, which included the Kaufman Assessment Battery for Children, Boston Naming Test, Beery Developmental Test of Visual-Motor Integration, and Grooved Pegboard Test...
August 24, 2017: Comprehensive Psychiatry
https://www.readbyqxmd.com/read/28944299/geographic-genetic-analysis-of-plasmodium-falciparum-parasite-populations-from-surveys-of-primary-school-children-in-western-kenya
#9
Irene Omedo, Polycarp Mogeni, Kirk Rockett, Alice Kamau, Christina Hubbart, Anna Jeffreys, Lynette Isabella Ochola-Oyier, Etienne P de Villiers, Caroline W Gitonga, Abdisalan M Noor, Robert W Snow, Dominic Kwiatkowski, Philip Bejon
Background. Malaria control, and finally malaria elimination, requires the identification and targeting of residual foci or hotspots of transmission. However, the level of parasite mixing within and between geographical locations is likely to impact the effectiveness and durability of control interventions and thus should be taken into consideration when developing control programs. Methods. In order to determine the geographic-genetic patterns of Plasmodium falciparum parasite populations at a sub-national level in Kenya, we used the Sequenom platform to genotype 111 genome-wide distributed single nucleotide polymorphic (SNP) positions in 2486 isolates collected from children in 95 primary schools in western Kenya...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28940308/safety-and-pharmacokinetics-of-the-oral-iron-chelator-sp-420-in-%C3%AE-thalassemia
#10
Ali T Taher, Antoine N Saliba, Kevin H Kuo, Patricia J Giardina, Alan R Cohen, Ellis J Neufeld, Yesim Aydinok, Janet L Kwiatkowski, Brenda I Jeglinski, Keith Pietropaolo, Gregory Berk, Vip Viprakasit
Our Phase I, open-label, multi-center, dose-escalation study evaluated the pharmacokinetics (PK) of SP-420, a tridentate oral iron chelating agent of the desferrithiocin class, in patients with transfusion dependent β-thalassemia. SP-420 was administered as a single dose of 1.5 (n=3), 3 (n=3), 6 (n=3), 12 (n=3), and 24 (n=6) mg/kg or as a twice-daily dose of 9 mg/kg (n=6) over 14-28 days. There was a near dose-linear increase in the mean plasma SP-420 concentrations and in the mean values for Cmax and AUC0-τ over the dose range evaluated...
September 22, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28938007/neuropilin-1-modulates-tgf%C3%AE-signaling-to-drive-glioblastoma-growth-and-recurrence-after-anti-angiogenic-therapy
#11
Sam C Kwiatkowski, Paola A Guerrero, Shinya Hirota, Zhihua Chen, John E Morales, Manish Aghi, Joseph H McCarty
Glioblastoma (GBM) is a rapidly progressive brain cancer that exploits the neural microenvironment, and particularly blood vessels, for selective growth and survival. Anti-angiogenic agents such as the vascular endothelial growth factor-A (VEGF-A) blocking antibody bevacizumab yield short-term benefits to patients due to blood vessel regression and stabilization of vascular permeability. However, tumor recurrence is common, and this is associated with acquired resistance to bevacizumab. The mechanisms that drive acquired resistance and tumor recurrence in response to anti-angiogenic therapy remain largely unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28923856/genomic-activation-of-pparg-reveals-a-candidate-therapeutic-axis-in-bladder-cancer
#12
Jonathan T Goldstein, Ashton C Berger, Juliann Shih, Fujiko F Duke, Laura Furst, David J Kwiatkowski, Andrew D Cherniack, Matthew Meyerson, Craig A Strathdee
The PPARG gene encoding the nuclear receptor PPAR-gamma is activated in bladder cancer, either directly by gene amplification or mutation, or indirectly by mutation of the RXRA gene which encodes the heterodimeric partner of PPAR-gamma. Here we show that activating alterations of PPARG or RXRA lead to a specific gene expression signature in bladder cancers. Reducing PPARG activity, whether by pharmacologic inhibition or genetic ablation, inhibited proliferation of PPARG-activated bladder cancer cells. Our results offer a preclinical proof of concept for PPARG as a candidate therapeutic target in bladder cancer...
September 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28917968/the-effect-of-fennel-essential-oil-in-combination-with-antibiotics-on-staphylococcus-aureus-strains-isolated-from-carriers
#13
Paweł Kwiatkowski, Magdalena Mnichowska-Polanowska, Agata Pruss, Helena Masiuk, Małgorzata Dzięcioł, Stefania Giedrys-Kalemba, Monika Sienkiewicz
An increase in the number of staphylococcal infections and carriers among medical staff has forced us to seek more and more effective antibacterial agents. Bacteria from the Staphylococcus genus possessing different mechanisms of resistance are the cause of nosocomial infections. The objective of our investigations was susceptibility of S. aureus strains isolated from nasal vestibule of medical students to fennel essential oil. The GC-MS analysis of fennel essential oil revealed eleven constituents among which a majority of trans-anethole (80%) was found...
November 2017: Burns: Journal of the International Society for Burn Injuries
https://www.readbyqxmd.com/read/28889816/first-stage-palliation-strategy-for-univentricular-heart-disease-may-impact-risk-for-acute-kidney-injury
#14
Bryan H Goldstein, Stuart L Goldstein, Prasad Devarajan, Farhan Zafar, David M Kwiatkowski, Bradley S Marino, David L S Morales, Catherine D Krawczeski, David S Cooper
OBJECTIVE: Norwood palliation for patients with single ventricle heart disease is associated with a significant risk for acute kidney injury, which portends a worse prognosis. We sought to investigate the impact of hybrid stage I palliation (Hybrid) on acute kidney injury risk. DESIGN: This study is a single-centre prospective case-control study of seven consecutive neonates with single ventricle undergoing Hybrid palliation. Levels of serum creatinine and four novel urinary biomarkers, namely neutrophil gelatinase-associated lipocalin, interleukin-18, liver fatty acid-binding protein, and kidney injury molecule-1, were obtained before and after palliation...
September 11, 2017: Cardiology in the Young
https://www.readbyqxmd.com/read/28878914/a-novel-keratin-13-variant-in-a-four-generation-family-with-white-sponge-nevus
#15
Stephanie B de Haseth, Egbert Bakker, Maarten H Vermeer, Hakima El Idrissi, Tjalling Bosse, Vincent T H B M Smit, Anna Terron-Kwiatkowski, W H Irwin McLean, Alexander A W Peters, Frederik J Hes
We report a novel KRT13 germ line variant that causes white sponge nevus (WSN) with mucosal dysplasia. Genital, vaginal, and cervical WSN were observed in four female patients, of whom two had premalignant cervical lesions at young age. Two of the 12 patients with oral WSN developed oral squamous cell carcinoma.
September 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28869989/reconciling-the-effects-of-screening-on-prostate-cancer-mortality-in-the-erspc-and-plco-trials
#16
Alex Tsodikov, Roman Gulati, Eveline A M Heijnsdijk, Paul F Pinsky, Sue M Moss, Sheng Qiu, Tiago M de Carvalho, Jonas Hugosson, Christine D Berg, Anssi Auvinen, Gerald L Andriole, Monique J Roobol, E David Crawford, Vera Nelen, Maciej Kwiatkowski, Marco Zappa, Marcos Luján, Arnauld Villers, Eric J Feuer, Harry J de Koning, Angela B Mariotto, Ruth Etzioni
Background: The ERSPC (European Randomized Study of Screening for Prostate Cancer) found that screening reduced prostate cancer mortality, but the PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) found no reduction. Objective: To evaluate whether effects of screening on prostate cancer mortality relative to no screening differed between the ERSPC and PLCO. Design: Cox regression of prostate cancer death in each trial group, adjusted for age and trial...
October 3, 2017: Annals of Internal Medicine
https://www.readbyqxmd.com/read/28865970/-description-of-the-gortec-2017-03-study-postoperative-stereotactic-radiotherapy-for-early-stage-oropharyngeal-and-oral-cavity-cancer-with-high-risk-margin-phrc-k-16-164
#17
MULTICENTER STUDY
J Biau, J Miroir, C Millardet, N Saroul, N Pham-Dang, S Racadot, F Huguet, F Kwiatkowski, B Pereira, J Bourhis, M Lapeyre
The GORTEC 2017-03-Stereo-postop study is a phase 2, multicentric, nationwide study, funded by the hospital clinical research program (PHRC). The sponsor is Centre Jean-Perrin in Clermont-Ferrand, in partnership with the GORTEC. The principal investigators are Dr J Biau and Dr M Lapeyre. The main objective is to study severe late toxicity of postoperative stereotactic radiotherapy (6×6Gy) for early stage oropharyngeal and oral cavity cancer with high risk margins. The secondary objectives include acute toxicity, efficacy, nutritional impact and quality of life...
October 2017: Cancer Radiothérapie: Journal de la Société Française de Radiothérapie Oncologique
https://www.readbyqxmd.com/read/28856135/plant-science-view-on-biohybrid-development
#18
REVIEW
Tomasz Skrzypczak, Rafał Krela, Wojciech Kwiatkowski, Shraddha Wadurkar, Aleksandra Smoczyńska, Przemysław Wojtaszek
Biohybrid consists of a living organism or cell and at least one engineered component. Designing robot-plant biohybrids is a great challenge: it requires interdisciplinary reconsideration of capabilities intimate specific to the biology of plants. Envisioned advances should improve agricultural/horticultural/social practice and could open new directions in utilization of plants by humans. Proper biohybrid cooperation depends upon effective communication. During evolution, plants developed many ways to communicate with each other, with animals, and with microorganisms...
2017: Frontiers in Bioengineering and Biotechnology
https://www.readbyqxmd.com/read/28851844/the-new-xpert-mtb-rif-ultra-improving-detection-of-mycobacterium-tuberculosis-and-resistance-to-rifampin-in-an-assay-suitable-for-point-of-care-testing
#19
Soumitesh Chakravorty, Ann Marie Simmons, Mazhgan Rowneki, Heta Parmar, Yuan Cao, Jamie Ryan, Padmapriya P Banada, Srinidhi Deshpande, Shubhada Shenai, Alexander Gall, Jennifer Glass, Barry Krieswirth, Samuel G Schumacher, Pamela Nabeta, Nestani Tukvadze, Camilla Rodrigues, Alena Skrahina, Elisa Tagliani, Daniela M Cirillo, Amy Davidow, Claudia M Denkinger, David Persing, Robert Kwiatkowski, Martin Jones, David Alland
The Xpert MTB/RIF assay (Xpert) is a rapid test for tuberculosis (TB) and rifampin resistance (RIF-R) suitable for point-of-care testing. However, it has decreased sensitivity in smear-negative sputum, and false identification of RIF-R occasionally occurs. We developed the Xpert MTB/RIF Ultra assay (Ultra) to improve performance. Ultra and Xpert limits of detection (LOD), dynamic ranges, and RIF-R rpoB mutation detection were tested on Mycobacterium tuberculosis DNA or sputum samples spiked with known numbers of M...
August 29, 2017: MBio
https://www.readbyqxmd.com/read/28830860/human-pluripotent-stem-cell-derived-tsc2-haploinsufficient-smooth-muscle-cells-recapitulate-features-of-lymphangioleiomyomatosis
#20
Lisa M Julian, Sean P Delaney, Ying Wang, Alexander A Goldberg, Carole Doré, Julien Yockell-Lelièvre, Roger Y Tam, Krinio Giannikou, Fiona McMurray, Molly S Shoichet, Mary-Ellen Harper, Elizabeth P Henske, David J Kwiatkowski, Thomas N Darling, Joel Moss, Arnold S Kristof, William L Stanford
Lymphangioleiomyomatosis (LAM) is a progressive destructive neoplasm of the lung associated with inactivating mutations in the TSC1 or TSC2 tumor suppressor genes. Cell or animal models that accurately reflect the pathology of LAM have been challenging to develop. Here, we generated a robust human cell model of LAM by reprogramming TSC2 mutation-bearing fibroblasts from a patient with both tuberous sclerosis complex (TSC) and LAM (TSC-LAM) into induced pluripotent stem cells (iPSC), followed by selection of cells that resemble those found in LAM tumors by unbiased in vivo differentiation...
October 15, 2017: Cancer Research
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