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https://www.readbyqxmd.com/read/28098952/solving-the-puzzle-of-one-carbon-loss-in-ripostatin-biosynthesis
#1
Chengzhang Fu, David Auerbach, Yanyan Li, Ullrich Scheid, Eva Luxenburger, Ronald Garcia, Herbert Irschik, Rolf Müller
Ripostatin is a promising antibiotic that inhibits RNA polymerase by binding to a novel binding site. In this study, the characterization of the biosynthetic gene cluster of ripostatin, which is a peculiar polyketide synthase (PKS) hybrid cluster encoding cis- and trans-acyltransferase PKS genes, is reported. Moreover, an unprecedented mechanism for phenyl acetic acid formation and loading as a starter unit was discovered. This phenyl-C2 unit is derived from phenylpyruvate (phenyl-C3) and the mechanism described herein explains the mysterious loss of one carbon atom in ripostatin biosynthesis from the phenyl-C3 precursor...
January 18, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28098860/chondroitin-sulfate-proteoglycan-protein-is-stimulated-by-interleukin%C3%A2-11-and-promotes-endometrial-epithelial-cancer-cell-proliferation-and-migration
#2
Amy Winship, Michelle Van Sinderen, Ariella Heffernan-Marks, Eva Dimitriadis
Endometrial cancer is the most common gynecological cancer. We identified interleukin 11 (IL11) as a critical mediator of endometrial tumourigenesis and demonstrated that IL11 regulates chondroitin sulfate proteoglycan (CSPG4) in human placental trophoblasts. CSPG4 is a cell membrane protein overexpressed in numerous human cancers, although its role in endometrial cancer has not been investigated. We examined CSPG4 expression and localization in primary human type I endometrioid grade (G) 1-3 tumours by qPCR and immunohistochemistry and determined whether IL11 stimulated CSPG4...
January 13, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28098756/detection-of-the-vascular-endothelial-growth-factor-with-a-novel-bioluminescence-resonance-energy-transfer-pair-using-a-two-component-system
#3
Tobias Wimmer, Eva Schroeter, Birgit Lorenz, Knut Stieger
In this paper we describe a two-component BRET (bioluminescence resonance energy transfer)-based method to detect vascular endothelial growth factor (VEGF) molecules in unknown samples as the basis for subsequent in vivo use. A luminescent VEGF binding molecule, which binds in the receptor binding motif of VEGF, is used as the energy donor, transferred to a fluorophore-coupled VEGF binding molecule (acceptor), which binds to the neuropilin binding motif of VEGF, thus enabling energy transfer from the donor to the acceptor molecule...
January 13, 2017: Sensors
https://www.readbyqxmd.com/read/28098724/central-macular-thickness-in-6-5-year-old-children-born-extremely-preterm-is-strongly-associated-with-gestational-age-even-when-adjusted-for-risk-factors
#4
Anna E C Molnar, Rebecka M Rosén, Maria Nilsson, Eva K B Larsson, Gerd E Holmström, Kerstin M Hellgren
PURPOSE: To assess the macular thickness in 6.5-year-old children born extremely preterm (EPT) in comparison with children born at term and to investigate risk factors associated with the macular thickness in the preterm group. METHODS: A population-based study of 6.5-year-old children born before the gestational age of 27 weeks and age-matched control subjects. Macular assessments with optical coherence tomography were performed, and the results were compared with neonatal risk factors and sex...
January 16, 2017: Retina
https://www.readbyqxmd.com/read/28098594/mediators-of-diabetic-neuropathy-is-hyperglycemia-the-only-culprit
#5
Anna Grisold, Brian C Callaghan, Eva L Feldman
PURPOSE OF REVIEW: Diabetic peripheral neuropathy (DPN) is a disabling, highly prevalent complication of both type 1 and type 2 diabetes mellitus (T1DM and T2DM). Large clinical studies support the concept that, in addition to hyperglycemia, components of the metabolic syndrome (MetS) may underlie the pathogenesis of DPN, especially in T2DM. This review will present the evidence supporting the MetS and its individual components as potential causal factors for the development of neuropathy...
January 16, 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/28098422/structural-elucidation-of-a-non-peptidic-inhibitor-specific-for-the-human-immunoproteasome
#6
Haissi Cui, Regina Baur, Camille Le Chapelain, Christian Dubiella, Wolfgang Heinemeyer, Eva Maria Huber, Michael Groll
Selective inhibition of the immunoproteasome is a promising approach towards the development of immunomodulatory drugs. Recently, a class of substituted thiazole compounds that combine a non-peptidic scaffold with the absence of an electrophile has been reported in a patent. Herein, we describe the mode of action of the lead compound using a sophisticated chimeric yeast model of the human immunoproteasome for structural studies. The inhibitor adopts a unique orientation perpendicular to the β5i substrate binding channel...
January 18, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28098159/fluid-shear-stress-activates-yap1-to-promote-cancer-cell-motility
#7
Hyun Jung Lee, Miguel F Diaz, Katherine M Price, Joyce A Ozuna, Songlin Zhang, Eva M Sevick-Muraca, John P Hagan, Pamela L Wenzel
Mechanical stress is pervasive in egress routes of malignancy, yet the intrinsic effects of force on tumour cells remain poorly understood. Here, we demonstrate that frictional force characteristic of flow in the lymphatics stimulates YAP1 to drive cancer cell migration; whereas intensities of fluid wall shear stress (WSS) typical of venous or arterial flow inhibit taxis. YAP1, but not TAZ, is strictly required for WSS-enhanced cell movement, as blockade of YAP1, TEAD1-4 or the YAP1-TEAD interaction reduces cellular velocity to levels observed without flow...
January 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28097765/a-false-positive-screening-hit-in-fragment-based-lead-discovery-watch-out-for-the-red-herring
#8
Jonathan Cramer, Johannes Schiebel, Tobias Wulsdorf, Kristof Grohe, Eszter Eva Najbauer, Frederik R Ehrmann, Nedyalka Radeva, Nina Zitzer, Uwe Linne, Rasmus Linser, Andreas Heine, Gerhard Klebe
With the rising popularity of fragment-based approaches in drug development, more and more attention has to be devoted to the detection of false-positive screening results. In particular, the small size and low affinity of fragments drives screening techniques to their limit. The pursuit of a false-positive hit can cause significant loss of time and resources. Here, we present an instructive and intriguing investigation into the origin of misleading assay results for a fragment that emerged as the most potent binder for the aspartic protease endothiapepsin (EP) across multiple screening assays...
January 18, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28097640/priming-increases-the-anti-tumor-effect-and-therapeutic-window-of-177-lu-octreotate-in-nude-mice-bearing-human-small-intestine-neuroendocrine-tumor-got1
#9
Johanna Dalmo, Johan Spetz, Mikael Montelius, Britta Langen, Yvonne Arvidsson, Henrik Johansson, Toshima Z Parris, Khalil Helou, Bo Wängberg, Ola Nilsson, Maria Ljungberg, Eva Forssell-Aronsson
BACKGROUND: (177)Lu-[DOTA(0), Tyr(3)]-octreotate ((177)Lu-octreotate) is used for treatment of patients with somatostatin receptor (SSTR) expressing neuroendocrine tumors. However, complete tumor remission is rarely seen, and optimization of treatment protocols is needed. In vitro studies have shown that irradiation can up-regulate the expression of SSTR1, 2 and 5, and increase (177)Lu-octreotate uptake. The aim of the present study was to examine the anti-tumor effect of a (177)Lu-octreotate priming dose followed 24 h later by a second injection of (177)Lu-octreotate compared to a single administration of (177)Lu-octreotate, performed on the human small intestine neuroendocrine tumor cell line, GOT1, transplanted to nude mice...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28097381/rotating-night-shift-work-sleep-and-colorectal-adenoma-in-women
#10
Elizabeth E Devore, Jennifer Massa, Kyriaki Papantoniou, Eva S Schernhammer, Kana Wu, Xuehong Zhang, Walter C Willett, Charles S Fuchs, Andrew T Chan, Shuji Ogino, Edward Giovannucci, Esther K Wei
PURPOSE: This study aims to investigate the associations of rotating night shift work history and sleep duration with risk of colorectal adenoma. METHODS: We evaluated 56,275 cancer-free participants of the Nurses' Health Study II, who had their first colonoscopy or sigmoidoscopy between 1991 and 2011; rotating night shift work and sleep duration were reported by mailed questionnaire. Multivariable-adjusted logistic regression was used to estimate relative risks (RR) of colorectal adenoma, with 95% confidence intervals (CI), across categories of rotating night shift work history (none, 1-4, 5-9, and ≥10 years) and sleep duration (≤5, 6, 7, 8, and ≥9 h/day)...
January 17, 2017: International Journal of Colorectal Disease
https://www.readbyqxmd.com/read/28096887/thylakoids-reduce-body-fat-and-fat-cell-size-by-binding-to-dietary-fat-making-it-less-available-for-absorption-in-high-fat-fed-mice
#11
Karin G Stenkula, Eva-Lena Stenblom, Caroline Montelius, Emil Egecioglu, Charlotte Erlanson-Albertsson
BACKGROUND: Dietary thylakoids derived from spinach have beneficial effects on body fat accumulation and blood lipids as demonstrated in humans and rodents. Important mechanisms established include delayed fat digestion in the intestine, without causing steatorrhea, and increased fatty acid oxidation in intestinal cells. The objective of our study was to elucidate if increased fecal fat excretion is an important mechanism to normalize adipose tissue metabolism during high-fat feeding in mice supplemented with thylakoids...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/28096664/predictors-of-outcomes-following-reablement-in-community-dwelling-older-adults
#12
Hanne Tuntland, Ingvild Kjeken, Eva Langeland, Bjarte Folkestad, Birgitte Espehaug, Oddvar Førland, Mona Kristin Aaslund
BACKGROUND: Reablement is a rehabilitation intervention for community-dwelling older adults, which has recently been implemented in several countries. Its purpose is to improve functional ability in daily occupations (everyday activities) perceived as important by the older person. Performance and satisfaction with performance in everyday life are the major outcomes of reablement. However, the evidence base concerning which factors predict better outcomes and who receives the greatest benefit in reablement is lacking...
2017: Clinical Interventions in Aging
https://www.readbyqxmd.com/read/28096513/targeting-tnfr2-with-antagonistic-antibodies-inhibits-proliferation-of-ovarian-cancer-cells-and-tumor-associated-tregs
#13
Heather Torrey, John Butterworth, Toshiyuki Mera, Yoshiaki Okubo, Limei Wang, Danielle Baum, Audrey Defusco, Sara Plager, Sarah Warden, Daniel Huang, Eva Vanamee, Rosemary Foster, Denise L Faustman
Major barriers to cancer therapy include the lack of selective inhibitors of regulatory T cells (Tregs) and the lack of broadly applicable ways to directly target tumors through frequently expressed surface oncogenes. Tumor necrosis factor receptor 2 (TNFR2) is an attractive target protein because of its restricted abundance to highly immunosuppressive Tregs and oncogenic presence on human tumors. We characterized the effect of TNFR2 inhibition using antagonistic antibodies. In culture-based assays, we found that two TNFR2 antagonists inhibited Treg proliferation, reduced soluble TNFR2 secretion from normal cells, and enabled T effector cell expansion...
January 17, 2017: Science Signaling
https://www.readbyqxmd.com/read/28096405/selenium-isotopes-record-extensive-marine-suboxia-during-the-great-oxidation-event
#14
Michael A Kipp, Eva E Stüeken, Andrey Bekker, Roger Buick
It has been proposed that an "oxygen overshoot" occurred during the early Paleoproterozoic Great Oxidation Event (GOE) in association with the extreme positive carbon isotopic excursion known as the Lomagundi Event. Moreover, it has also been suggested that environmental oxygen levels then crashed to very low levels during the subsequent extremely negative Shunga-Francevillian carbon isotopic anomaly. These redox fluctuations could have profoundly influenced the course of eukaryotic evolution, as eukaryotes have several metabolic processes that are obligately aerobic...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096235/role-of-cardiotrophin-1-in-the-regulation-of-metabolic-circadian-rhythms-and-adipose-core-clock-genes-in-mice-and-characterization-of-24-h-circulating-ct-1-profiles-in-normal-weight-and-overweight-obese-subjects
#15
Miguel López-Yoldi, Kimber L Stanhope, Marta Garaulet, X Guoxia Chen, Beatriz Marcos-Gómez, María Paz Carrasco-Benso, Eva M Santa Maria, Xavier Escoté, Vivien Lee, Marinelle V Nunez, Valentina Medici, Eduardo Martínez-Ansó, Neira Sáinz, Ana E Huerta, Laura M Laiglesia, Jesús Prieto, J Alfredo Martínez, Matilde Bustos, Peter J Havel, Maria J Moreno-Aliaga
Cardiotrophin (CT)-1 is a regulator of glucose and lipid homeostasis. In the present study, we analyzed whether CT-1 also acts to peripherally regulate metabolic rhythms and adipose tissue core clock genes in mice. Moreover, the circadian pattern of plasma CT-1 levels was evaluated in normal-weight and overweight subjects. The circadian rhythmicity of oxygen consumption rate (Vo2) was disrupted in aged-obese CT-1-deficient (CT-1(-/-)) mice (12 mo). Although circadian rhythms of Vo2 were conserved in young-lean CT-1(-/-) mice (2 mo), CT-1 deficiency caused a phase shift of the acrophase...
January 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28095796/a-severe-case-of-visceral-leishmaniasis-and-liposomal-amphotericin-b-treatment-failure-in-an-immunosuppressed-patient-15%C3%A2-years-after-exposure
#16
Anna Eichenberger, Annina E Buechi, Andreas Neumayr, Chistroph Hatz, Andri Rauch, Marc Huguenot, Eva Diamantis-Karamitopoulou, Cornelia Staehelin
BACKGROUND: Visceral leishmaniasis (VL) is a protozoan disease, which is responsible for 200.000-400.000 yearly infections worldwide. If left untreated, the fatality rate can be as high as 100% within 2 years. 90% of cases occur in just six countries: India, Bangladesh, Sudan, South Sudan, Ethiopia and Brazil. It is thus a disease rarely seen by physicians in Europe or North America. We report on the fatal case of VL in an 80-year-old immunosuppressed patient who presented with a latency of over 15 years after having visited an endemic region...
January 17, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28095331/the-effect-of-combined-avoidance-and-control-training-on-implicit-food-evaluation-and-choice
#17
Naomi Kakoschke, Eva Kemps, Marika Tiggemann
BACKGROUND: Continual exposure to food cues in the environment contributes to unhealthy eating behaviour. According to dual-process models, such behaviour is partly determined by automatic processing of unhealthy food cues (e.g., approach bias), which fails to be regulated by controlled processing (e.g., inhibitory control). The current study aimed to investigate the effect of combined avoidance and control training on implicit evaluation (liking), choice, and consumption of unhealthy snack food...
January 5, 2017: Journal of Behavior Therapy and Experimental Psychiatry
https://www.readbyqxmd.com/read/28095284/family-carers-perspectives-on-integrated-community-care-in-the-czech-republic
#18
Eva Křížová, Hana Janečková, Jaromír Běláček
AIM: The problem of family care for people dependent on another person has only recently become a focus of research. As demand for health and social services has not been adequately met by public service providers, growing attention has been given to informal care and the integration of families within systems of health and social care at the community level. This paper presents the results of a survey on informal carers' views and opinions under the current conditions of social support in the Czech Republic...
December 2016: Central European Journal of Public Health
https://www.readbyqxmd.com/read/28095281/nurses-attitudes-toward-intervening-with-smokers-their-knowledge-opinion-and-e-learning-impact
#19
Eva Králíková, Vladislava Felbrová, Stanislava Kulovaná, Kateřina Malá, Iveta Nohavová, Eva Roubíčková, Alexandra Pánková, Stella A Bialous, Marjorie J Wells, Jenny Brook, Linda Sarna
BACKGROUND: Numbering about 90,000, nurses represent the largest group of health care providers in the Czech Republic. Therefore, nurses can make a significant impact in the treatment of tobacco dependence, particularly in applying brief interventions to smokers. METHODS: During 2014, 279 nurses from the Czech Republic participated in an e-learning education programme consisting of two Webcasts with additional web-based resources about smoking cessation in relation to health and treatment options in daily clinical practice, particularly regarding brief intervention methods...
December 2016: Central European Journal of Public Health
https://www.readbyqxmd.com/read/28095253/lichen-microalgae-are-sensitive-to-environmental-concentrations-of-atrazine
#20
Helena Moreno Traba, Noelia Domínguez-Morueco, Eva Barreno, Myriam Catalá
The identification of new organisms for environmental toxicology bioassays is currently a priority, since these tools are strongly limited by the ecological relevance of taxa used to study global change. Lichens are sensitive bioindicators of air quality and their microalgae are an untapped source for new low-cost miniaturized bioassays with ecological importance. In order to increase the availability of a wider range of taxa for bioassays, the sensitivity of two symbiotic lichen microalgae, Asterochloris erici and Trebouxia sp...
January 17, 2017: Journal of Environmental Science and Health. Part. B, Pesticides, Food Contaminants, and Agricultural Wastes
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