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https://www.readbyqxmd.com/read/27921095/journey-from-the-center-of-the-cell-the-intra-and-intercellular-transport-of-mrna
#1
Anna Kasprowicz-Maluśki, Wojciech Kwiatkowski, Alicja Starosta, Przemysław Wojtaszek
Transport and localized translation of mRNA is crucial for the proper spatiotemporal organization of proteins within cells. Distribution of RNAs to subcellular domains has recently emerged as a major mechanism for establishing functionally distinct compartments and structures in the cells. There is an emerging evidence that active transport of mRNA involves cytoskeleton and membrane trafficking pathways in fungi, plants and animals, suggesting that it is a common phenomenon among eukaryotes. The important highlights are that the RNA-binding proteins recognize the cargo mRNA and that RNPs are actively transported on the cytoskeletal tracks or co-transported with membranous compartments, such as the endoplasmic reticulum and endosomes...
December 6, 2016: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/27918305/tuberous-sclerosis-complex-inactivation-disrupts-melanogenesis-via-mtorc1-activation
#2
Juxiang Cao, Magdalena E Tyburczy, Joel Moss, Thomas N Darling, Hans R Widlund, David J Kwiatkowski
Tuberous sclerosis complex (TSC) is an autosomal dominant tumor-suppressor gene syndrome caused by inactivating mutations in either TSC1 or TSC2, and the TSC protein complex is an essential regulator of mTOR complex 1 (mTORC1). Patients with TSC develop hypomelanotic macules (white spots), but the molecular mechanisms underlying their formation are not fully characterized. Using human primary melanocytes and a highly pigmented melanoma cell line, we demonstrate that reduced expression of either TSC1 or TSC2 causes reduced pigmentation through mTORC1 activation, which results in hyperactivation of glycogen synthase kinase 3β (GSK3β), followed by phosphorylation of and loss of β-catenin from the nucleus, thereby reducing expression of microphthalmia-associated transcription factor (MITF), and subsequent reductions in tyrosinase and other genes required for melanogenesis...
December 5, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27907099/analysis-of-a-mouse-skin-model-of-tuberous-sclerosis-complex
#3
Yanan Guo, John R Dreier, Juxiang Cao, Heng Du, Scott R Granter, David J Kwiatkowski
Tuberous Sclerosis Complex (TSC) is an autosomal dominant tumor suppressor gene syndrome in which patients develop several types of tumors, including facial angiofibroma, subungual fibroma, Shagreen patch, angiomyolipomas, and lymphangioleiomyomatosis. It is due to inactivating mutations in TSC1 or TSC2. We sought to generate a mouse model of one or more of these tumor types by targeting deletion of the Tsc1 gene to fibroblasts using the Fsp-Cre allele. Mutant, Tsc1ccFsp-Cre+ mice survived a median of nearly a year, and developed tumors in multiple sites but did not develop angiomyolipoma or lymphangioleiomyomatosis...
2016: PloS One
https://www.readbyqxmd.com/read/27899999/colorectal-cancer-patients-exhibit-increased-levels-of-galanin-in-serum-and-colon-tissues
#4
Przemysław Kwiatkowski, Janusz Godlewski, Jacek Kieżun, Bartłomiej Emil Kraziński, Zbigniew Kmieć
Galanin (GAL) is a 30-amino acid neuropeptide that is expressed in both the central and peripheral nervous system, including the enteric nervous system (ENS). Increased GAL concentrations have been identified in the blood of colorectal cancer (CRC) patients. The aim of the present study was to assess whether sections of the colon wall containing ENS plexuses or CRC tumor are associated with increased GAL concentrations. Blood samples were collected from 68 CRC patients and 39 healthy volunteers. In addition, samples of CRC tumors and colon wall tissue in close proximity to and distant from the neoplastic tissue were obtained from 22 CRC patients...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899115/characterizing-the-impact-of-sustained-sulfadoxine-pyrimethamine-use-upon-the-plasmodium-falciparum-population-in-malawi
#5
Matt Ravenhall, Ernest Diez Benavente, Mwapatsa Mipando, Anja T R Jensen, Colin J Sutherland, Cally Roper, Nuno Sepúlveda, Dominic P Kwiatkowski, Jacqui Montgomery, Kamija S Phiri, Anja Terlouw, Alister Craig, Susana Campino, Harold Ocholla, Taane G Clark
BACKGROUND: Malawi experienced prolonged use of sulfadoxine/pyrimethamine (SP) as the front-line anti-malarial drug, with early replacement of chloroquine and delayed introduction of artemisinin-based combination therapy. Extended use of SP, and its continued application in pregnancy is impacting the genomic variation of the Plasmodium falciparum population. METHODS: Whole genome sequence data of P. falciparum isolates covering 2 years of transmission within Malawi, alongside global datasets, were used...
November 29, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27898193/modeling-long-term-changes-in-tundra-carbon-balance-following-wildfire-climate-change-and-potential-nutrient-addition
#6
Yueyang Jiang, Edward B Rastetter, Gaius R Shaver, Adrian V Rocha, Qianlai Zhuang, Bonnie L Kwiatkowski
To investigate the underlying mechanisms that control long-term recovery of tundra carbon (C) and nutrients after fire, we employed the Multiple Element Limitation (MEL) model to simulate 200-yr post-fire changes in the biogeochemistry of three sites along a burn severity gradient in response to increases in air temperature, CO2 concentration, nitrogen (N) deposition, and phosphorus (P) weathering rates. The simulations were conducted for severely burned, moderately burned, and unburned arctic tundra. Our simulations indicated that recovery of C balance after fire was mainly determined by the internal redistribution of nutrients among ecosystem components (controlled by air temperature), rather than the supply of nutrients from external sources (e...
August 4, 2016: Ecological Applications: a Publication of the Ecological Society of America
https://www.readbyqxmd.com/read/27895843/severe-anemia-in-malawian-children
#7
Job Cj Calis, Kamija S Phiri, E Brian Faragher, Bernard J Brabin, Imelda Bates, Luis E Cuevas, Rob J de Haan, Ajib I Phiri, Pelani Malange, Mirriam Khoka, Paul Jm Hulshof, Lisette van Lieshout, Marcel Ghm Beld, Yik Y Teo, Kirk A Rockett, Anna Richardson, Dominic P Kwiatkowski, Malcolm E Molyneux, Michaël Boele van Hensbroek
BACKGROUND: Severe anemia is a major cause of sickness and death in African children, yet the causes of anemia in this population have been inadequately studied. METHODS: We conducted a case-control study of 381 preschool children with severe anemia (hemoglobin concentration, <5.0 g per deciliter) and 757 preschool children without severe anemia in urban and rural settings in Malawi. Causal factors previously associated with severe anemia were studied. The data were examined by multivariate analysis and structural equation modeling...
September 2016: Malawi Medical Journal: the Journal of Medical Association of Malawi
https://www.readbyqxmd.com/read/27882345/institutional-implementation-of-clinical-tumor-profiling-on-an-unselected-cancer-population
#8
Lynette M Sholl, Khanh Do, Priyanka Shivdasani, Ethan Cerami, Adrian M Dubuc, Frank C Kuo, Elizabeth P Garcia, Yonghui Jia, Phani Davineni, Ryan P Abo, Trevor J Pugh, Paul van Hummelen, Aaron R Thorner, Matthew Ducar, Alice H Berger, Mizuki Nishino, Katherine A Janeway, Alanna Church, Marian Harris, Lauren L Ritterhouse, Joshua D Campbell, Vanesa Rojas-Rudilla, Azra H Ligon, Shakti Ramkissoon, James M Cleary, Ursula Matulonis, Geoffrey R Oxnard, Richard Chao, Vanessa Tassell, James Christensen, William C Hahn, Philip W Kantoff, David J Kwiatkowski, Bruce E Johnson, Matthew Meyerson, Levi A Garraway, Geoffrey I Shapiro, Barrett J Rollins, Neal I Lindeman, Laura E MacConaill
BACKGROUND. Comprehensive genomic profiling of a patient's cancer can be used to diagnose, monitor, and recommend treatment. Clinical implementation of tumor profiling in an enterprise-wide, unselected cancer patient population has yet to be reported. METHODS. We deployed a hybrid-capture and massively parallel sequencing assay (OncoPanel) for all adult and pediatric patients at our combined cancer centers. Results were categorized by pathologists based on actionability. We report the results for the first 3,727 patients tested...
November 17, 2016: JCI Insight
https://www.readbyqxmd.com/read/27869053/incidence-risk-factors-and-outcomes-of-acute-kidney-injury-in-adults-undergoing-surgery-for-congenital-heart-disease
#9
David M Kwiatkowski, Elizabeth Price, David M Axelrod, Anitra W Romfh, Brian S Han, Scott M Sutherland, Catherine D Krawczeski
BACKGROUND: Acute kidney injury after cardiac surgery is a frequent and serious complication among children with congenital heart disease (CHD) and adults with acquired heart disease; however, the significance of kidney injury in adults after congenital heart surgery is unknown. The primary objective of this study was to determine the incidence of acute kidney injury after surgery for adult CHD. Secondary objectives included determination of risk factors and associations with clinical outcomes...
November 21, 2016: Cardiology in the Young
https://www.readbyqxmd.com/read/27866211/single-nucleotide-polymorphisms-of-genes-involved-in-repair-of-oxidative-dna-damage-and-the-risk-of-recurrent-depressive-disorder
#10
Piotr Czarny, Dominik Kwiatkowski, Monika Toma, Piotr Gałecki, Agata Orzechowska, Kinga Bobińska, Anna Bielecka-Kowalska, Janusz Szemraj, Michael Berk, George Anderson, Tomasz Śliwiński
BACKGROUND Depressive disorder, including recurrent type (rDD), is accompanied by increased oxidative stress and activation of inflammatory pathways, which may induce DNA damage. This thesis is supported by the presence of increased levels of DNA damage in depressed patients. Such DNA damage is repaired by the base excision repair (BER) pathway. BER efficiency may be influenced by polymorphisms in BER-related genes. Therefore, we genotyped nine single-nucleotide polymorphisms (SNPs) in six genes encoding BER proteins...
November 20, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27866183/resolution-of-allergic-rhinitis-and-reactive-bronchospasm-with-supplements-and-food-specific-immunoglobulin-g-elimination-a-case-report
#11
Laura Kwiatkowski, Jessica Mitchell, Jeffrey Langland
Context • Allergies are a common affliction, whether they are respiratory, food related, or dermatological. People often resort to continuous use of over-the-counter medications, such as antihistamines, to manage their symptoms. Controversy still remains over testing serum immunoglobulin (Ig) G to diagnose food allergies. Objective • This study intended to examine the benefits of treatment of a pediatric patient with natural supplements and an elimination diet for IgG food allergies. Design • The research team reported a case study...
October 2016: Alternative Therapies in Health and Medicine
https://www.readbyqxmd.com/read/27865093/maternal-endothelial-damage-as-a-disorder-shared-by-early-preeclampsia-late-preeclampsia-and-intrauterine-growth-restriction
#12
Sebastian Kwiatkowski, Barbara Dołegowska, Ewa Kwiatkowska, Rafał Rzepka, Natalia Marczuk, Beata Loj, Andrzej Torbè
INTRODUCTION: Preeclampsia (PE) and intrauterine growth restriction (IUGR) are separate disease entities that have frequently been reported as sharing the same pathogenesis. In both of them, angiogenesis disorders and generalized endothelial damage with an accompanying inflammation are the dominant symptoms. In this study, we attempted to prove that both these processes demonstrate the same profile in early PE, late PE and IUGR patients, while the only difference is in the degree of exacerbation of the lesions...
November 19, 2016: Journal of Perinatal Medicine
https://www.readbyqxmd.com/read/27855442/impact-of-cause-of-death-adjudication-on-the-results-of-the-european-prostate-cancer-screening-trial
#13
Stephen D Walter, Harry J de Koning, Jonas Hugosson, Kirsi Talala, Monique J Roobol, Sigrid Carlsson, Marco Zappa, Vera Nelen, Maciej Kwiatkowski, Álvaro Páez, Sue Moss, Anssi Auvinen
BACKGROUND: The European Randomised Study of Prostate Cancer Screening has shown a 21% relative reduction in prostate cancer mortality at 13 years. The causes of death can be misattributed, particularly in elderly men with multiple comorbidities, and therefore accurate assessment of the underlying cause of death is crucial for valid results. To address potential unreliability of end-point assessment, and its possible impact on mortality results, we analysed the study outcome adjudication data in six countries...
November 17, 2016: British Journal of Cancer
https://www.readbyqxmd.com/read/27829940/cross-sectional-study-of-male-sexual-function-in-bariatric-patients
#14
Michał R Janik, Ilona Bielecka, Andrzej Kwiatkowski, Piotr E Janik, Thomas Drazba, Jan Bujok, Edward Stanowski, Krzysztof Paśnik
INTRODUCTION: Obesity is associated with numerous comorbidities and affects various aspects of life, including sexual functioning. Bariatric surgery is an effective treatment for obese people. Male sexual function after bariatric surgery is not well known. AIM: To compare male sexual function and sexual quality of life after surgical weight loss with controls seeking bariatric surgery. MATERIAL AND METHODS: International Index of Erectile Function and Sexual Quality of Life-Male (SQoL-M) questionnaires were administered by e-mail to 152 men who had undergone weight-loss surgery...
2016: Wideochirurgia i Inne Techniki Mało Inwazyjne, Videosurgery and Other Miniinvasive Techniques
https://www.readbyqxmd.com/read/27829937/the-effect-of-oversewing-the-staple-line-in-laparoscopic-sleeve-gastrectomy-randomized-control-trial
#15
Andrzej Kwiatkowski, Michał R Janik, Krzysztof Paśnik, Edward Stanowski
INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) is one of the most popular bariatric procedures. The procedure is associated with serious staple-line complications such as bleeding, leaks, and stenosis. AIM: To determine whether oversewing the staple line, compared with clipping, in LSG reduces the incidence of postoperative bleeding. MATERIAL AND METHODS: We conducted a parallel-group, prospective, randomized controlled trial (RCT) of 100 patients who underwent LSG for obesity at a single institution between May 2014 and August 2015...
2016: Wideochirurgia i Inne Techniki Mało Inwazyjne, Videosurgery and Other Miniinvasive Techniques
https://www.readbyqxmd.com/read/27825693/use-of-nitroglycerin-by-bolus-prevents-intensive-care-unit-admission-in-patients-with-acute-hypertensive-heart-failure
#16
Suprat Saely Wilson, Gregory M Kwiatkowski, Scott R Millis, John D Purakal, Arushi P Mahajan, Phillip D Levy
OBJECTIVES: The purpose of this study was to compare health care resource utilization among patients who were given intravenous nitroglycerin for acute heart failure (AHF) in the emergency department (ED) by intermittent bolus, continuous infusion, or a combination of both. METHODS: We retrospectively identified 395 patients that received nitroglycerin therapy in the ED for the treatment of AHF over a 5-year period. Patients that received intermittent bolus (n=124) were compared with continuous infusion therapy (n=182) and combination therapy of bolus and infusion (n=89)...
October 18, 2016: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/27825353/analysis-of-anti-malarial-resistance-markers-in-pfmdr1-and-pfcrt-across-southeast-asia-in-the-tracking-resistance-to-artemisinin-collaboration
#17
Krongkan Srimuang, Olivo Miotto, Pharath Lim, Rick M Fairhurst, Dominic P Kwiatkowski, Charles J Woodrow, Mallika Imwong
BACKGROUND: Declining anti-malarial efficacy of artemisinin-based combination therapy, and reduced Plasmodium falciparum susceptibility to individual anti-malarials are being documented across an expanding area of Southeast Asia (SEA). Genotypic markers complement phenotypic studies in assessing the efficacy of individual anti-malarials. METHODS: The markers pfmdr1 and pfcrt were genotyped in parasite samples obtained in 2011-2014 at 14 TRAC (Tracking Resistance to Artemisinin Collaboration) sites in mainland Southeast Asia using a combination of PCR and next-generation sequencing methods...
November 8, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27818095/genetic-markers-associated-with-dihydroartemisinin-piperaquine-failure-in-plasmodium-falciparum-malaria-in-cambodia-a-genotype-phenotype-association-study
#18
Roberto Amato, Pharath Lim, Olivo Miotto, Chanaki Amaratunga, Dalin Dek, Richard D Pearson, Jacob Almagro-Garcia, Aaron T Neal, Sokunthea Sreng, Seila Suon, Eleanor Drury, Dushyanth Jyothi, Jim Stalker, Dominic P Kwiatkowski, Rick M Fairhurst
BACKGROUND: As the prevalence of artemisinin-resistant Plasmodium falciparum malaria increases in the Greater Mekong subregion, emerging resistance to partner drugs in artemisinin combination therapies seriously threatens global efforts to treat and eliminate this disease. Molecular markers that predict failure of artemisinin combination therapy are urgently needed to monitor the spread of partner drug resistance, and to recommend alternative treatments in southeast Asia and beyond. METHODS: We did a genome-wide association study of 297 P falciparum isolates from Cambodia to investigate the relationship of 11 630 exonic single-nucleotide polymorphisms (SNPs) and 43 copy number variations (CNVs) with in-vitro piperaquine 50% inhibitory concentrations (IC50s), and tested whether these genetic variants are markers of treatment failure with dihydroartemisinin-piperaquine...
November 3, 2016: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/27813682/challenges-in-translation-lessons-from-using-business-pedagogy-to-teach-leadership-in-undergraduate-medicine
#19
Dani C Cadieux, Lorelei Lingard, Daniela Kwiatkowski, Teresa Van Deven, Murray Bryant, Gary Tithecott
PROBLEM: Leadership is increasingly recognized as a core physician competency required for quality patient care, continual system improvement, and optimal healthcare team performance. Consequently, integration of leadership into medical school curriculum is becoming a priority. This raises the question of the appropriate context, timing, and pedagogy for conveying this competency to medical students. INTERVENTION: Our program introduced a 1-week leadership course grounded in business pedagogy to Year 1 medical students...
November 4, 2016: Teaching and Learning in Medicine
https://www.readbyqxmd.com/read/27798646/independent-origin-and-global-distribution-of-distinct-plasmodium-vivax-duffy-binding-protein-gene-duplications
#20
Jessica B Hostetler, Eugenia Lo, Usheer Kanjee, Chanaki Amaratunga, Seila Suon, Sokunthea Sreng, Sivanna Mao, Delenasaw Yewhalaw, Anjali Mascarenhas, Dominic P Kwiatkowski, Marcelo U Ferreira, Pradipsinh K Rathod, Guiyun Yan, Rick M Fairhurst, Manoj T Duraisingh, Julian C Rayner
BACKGROUND: Plasmodium vivax causes the majority of malaria episodes outside Africa, but remains a relatively understudied pathogen. The pathology of P. vivax infection depends critically on the parasite's ability to recognize and invade human erythrocytes. This invasion process involves an interaction between P. vivax Duffy Binding Protein (PvDBP) in merozoites and the Duffy antigen receptor for chemokines (DARC) on the erythrocyte surface. Whole-genome sequencing of clinical isolates recently established that some P...
October 2016: PLoS Neglected Tropical Diseases
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