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James R Blum, Elliot J Rayfield
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March 2018: Endocrine Practice
Sigrun Schmähling, Arno Meiler, Yoonjung Lee, Arif Mohammed, Katja Finkl, Katharina Tauscher, Lars Israel, Marc Borath, Julia Philippou-Massier, Helmut Blum, Bianca Habermann, Axel Imhof, Ji-Joon Song, Jürg Müller
The Drosophila Ash1 protein is a trithorax-group (trxG) regulator that antagonizes Polycomb repression at HOX genes. Ash1 di-methylates lysine 36 in histone H3 (H3K36me2) but how this activity is controlled and at which genes it functions is not well understood. We show that Ash1 protein purified from Drosophila exists in a complex with MRG15 and Caf1 that we named AMC. In Drosophila and human AMC, MRG15 binds a conserved FxLP motif near the Ash1 SET domain and stimulates H3K36 di-methylation on nucleosomes...
March 14, 2018: Development
F Meyer, M Blum, A Benkert, D Hauschild, Y L Jeyachandran, R G Wilks, W Yang, M Bär, F Reinert, C Heske, M Zharnikov, L Weinhardt
The occupied and unoccupied electronic structure of imidazole (C3 N2 H4 ) and imidazolium (C3 N2 H5 + ) in aqueous solutions is studied by X-ray emission spectroscopy (XES) and resonant inelastic soft X-ray scattering (RIXS). Both systems show distinct RIXS fingerprints with strong resonant effects. A comparison with calculated X-ray emission spectra of isolated imidazole and imidazolium suggests only a small influence of hydrogen bonding in the aqueous solution on the electronic structure of imidazole and imidazolium, and allows the attribution of specific spectral features to the non-equivalent nitrogen and carbon atoms in the molecules...
March 13, 2018: Physical Chemistry Chemical Physics: PCCP
Stephane Jeanmart, Julien Gagnepain, Pulakesh Maity, Clemens Lamberth, Fredrik Cederbaum, Ramya Rajan, Olivier Jacob, Mathias Blum, Stephane Bieri
Novel imidazole-based ketene dithioacetals show impressive in planta activity against the economically important plant pathogens Alternaria solani, Botryotinia fuckeliana, Erysiphe necator and Zymoseptoria tritici. Especially derivatives of the topical antifungal lanoconazole, which bear an alkynyloxy or a heteroaryl group in the para-position of the phenyl ring, exhibit excellent control of the mentioned phytopathogens. These compounds inhibit 14α -demethylase in the sterol biosynthesis pathway of the fungi...
March 9, 2018: Bioorganic & Medicinal Chemistry
Soujanya Sunkaraneni, Elizabeth A Ludwig, Julie A Passarell, David Blum, Todd Grinnell, Jill Fiedler-Kelly
Eslicarbazepine acetate (ESL) is a once-daily oral antiepileptic drug (AED) indicated for partial-onset seizures (POS). ESL pharmacokinetics (PK) and exposure-response analyses were supported by 2 phase 3 conversion to ESL (1200, 1600 mg) monotherapy studies. The PK model development included 10 phase 1-2 studies (ESL 600-1200 mg daily). Seizure diaries were completed daily; subjects exited if seizures worsened. Exposure-response models were developed for time to study exit, probability of seizure freedom, time to first occurrence of dizziness, headache, and nausea; serum sodium levels were explored...
March 12, 2018: Journal of Clinical Pharmacology
M Q Chan, A E Blum, A K Chandar, A M L Kieber Emmons, Y Shindo, W Brock, G W Falk, M I Canto, J S Wang, P G Iyer, N J Shaheen, W M Grady, J A Abrams, P N Thota, K K Guda, A Chak
Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC). Based on striking aggregation of breast cancer and BE/EAC within families as well as shared risk factors and molecular mechanisms of carcinogenesis, we hypothesized that BE may be associated with breast cancer. Pedigree analysis of families identified prospectively at multiple academic centers as part of the Familial Barrett's Esophagus Consortium (FBEC) was reviewed and families with aggregation of BE/EAC and breast cancer are reported...
March 7, 2018: Diseases of the Esophagus: Official Journal of the International Society for Diseases of the Esophagus
Dena Eltahlah, Christopher D Lynch, Barbara L Chadwick, Igor R Blum, Nairn H F Wilson
AIM: The aim of this study was to review patterns of restoration placement and replacement. A previous study had been carried out in the late 1990s and this study sought to update the literature in this important aspect of dental practice. METHOD: Studies based on the protocol of Mjör (1981) were selected. Such studies involved participating dentists completing a proforma each time a patient presented for a new or replacement restoration. RESULTS: Twenty-five papers were included in this study, of which 12 were included in the original review...
March 6, 2018: Journal of Dentistry
Jason D Demers, Joel D Blum, Scott C Brooks, Patrick M Donovan, Ami L Riscassi, Carrie L Miller, Wang Zheng, Baohua Gu
Natural abundance stable Hg isotope measurements were used to place new constraints on sources, transport, and transformations of Hg along the flow path of East Fork Poplar Creek (EFPC), a point-source contaminated headwater stream in Oak Ridge, Tennessee. Particulate-bound Hg in the water column of EFPC within the Y-12 National Security Complex, was isotopically similar to average metallic Hg(0) used in industry, having a mean δ202 Hg value of -0.42 ± 0.09‰ (1SD) and near-zero Δ199 Hg. On average, particulate fraction δ202 Hg values increased downstream by 0...
March 9, 2018: Environmental Science. Processes & Impacts
Fahim Ebrahimi, Stavros Giaglis, Sinuhe Hahn, Claudine A Blum, Christine Baumgartner, Alexander Kutz, Shane Vontelin van Breda, Beat Mueller, Philipp Schuetz, Mirjam Christ-Crain, Paul Hasler
Neutrophil extracellular traps (NETs) are a hallmark of the immune response in inflammatory diseases. However, the role of NETs in community-acquired pneumonia is unknown. This study aims to characterise the impact of NETs on clinical outcomes in pneumonia.This is a secondary analysis of a randomized-controlled, multicentre trial. Patients with community-acquired pneumonia were randomly assigned to either prednisone 50 mg or placebo for 7 days. The primary endpoint was time to clinical stability; main secondary endpoints were length of hospital stay and mortality...
March 8, 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Karen M Davies, Thorsten B Blum, Werner Kühlbrandt
We used electron cryo-tomography and subtomogram averaging to investigate the structure of complex I and its supramolecular assemblies in the inner mitochondrial membrane of mammals, fungi, and plants. Tomographic volumes containing complex I were averaged at ∼4 nm resolution. Principal component analysis indicated that ∼60% of complex I formed a supercomplex with dimeric complex III, while ∼40% were not associated with other respiratory chain complexes. The mutual arrangement of complex I and III2 was essentially conserved in all supercomplexes investigated...
March 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
Crystal C Walline, Janice S Blum, Tobyn Linton, Darrin Mangiacarne, Suthat Liangpunsakul
Excessive drinking can lead to the development of immune dysfunction. Our aim is to investigate the effect of alcohol on immune activation from circulating peripheral blood monocytes in excessive drinkers (EDs). Twenty-two EDs and healthy controls were enrolled. Time line follow-back was used to quantify the amount of alcohol consumed in the past 30 days before enrollment. Peripheral blood-derived CD14+ monocytes were isolated for gene expression analyses. Serum interleukin (IL)-6, IL-10 and lipopolysaccharides (LPS) were also measured...
March 8, 2018: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
Bhavani Gopalakrishnan, Carolyn Cheney, Rajeswaran Mani, Xiaokui Mo, Donna Bucci, Alison Walker, Rebecca Klisovic, Bhavana Bhatnagar, Katherine Walsh, Bjoern Rueter, Irene C Waizenegger, Karl-Heinz Heider, William Blum, Sumithira Vasu, Natarajan Muthusamy
Acute myeloid leukemia (AML) is the second most common type of leukemia in adults. Incidence of AML increases with age with a peak incidence at 67 years. Patients older than 60 years have an unfavorable prognosis due to resistance to conventional chemotherapy. Volasertib (BI 6727) is a cell-cycle regulator targeting polo-like kinase which has been evaluated in clinical trials in AML. We evaluated effects of volasertib in primary patient samples and NK cells. At equivalent doses, volasertib is cytotoxic to AML blasts but largely spares healthy NK cells...
February 9, 2018: Oncotarget
C Desert, E Baéza, M Aite, M Boutin, A Le Cam, J Montfort, M Houee-Bigot, Y Blum, P F Roux, C Hennequet-Antier, C Berri, S Metayer-Coustard, A Collin, S Allais, E Le Bihan, D Causeur, F Gondret, M J Duclos, S Lagarrigue
BACKGROUND: Because the cost of cereals is unstable and represents a large part of production charges for meat-type chicken, there is an urge to formulate alternative diets from more cost-effective feedstuff. We have recently shown that meat-type chicken source is prone to adapt to dietary starch substitution with fat and fiber. The aim of this study was to better understand the molecular mechanisms of this adaptation to changes in dietary energy sources through the fine characterization of transcriptomic changes occurring in three major metabolic tissues - liver, adipose tissue and muscle - as well as in circulating blood cells...
March 7, 2018: BMC Genomics
Dana Rose Garfin, Michael J Poulin, Scott Blum, Roxane Cohen Silver
Research conducted in the early years after the September 11, 2001 (9/11) terrorist attacks in New York, Pennsylvania, and Washington, DC demonstrated adverse psychological outcomes among residents of the United States who were exposed to the attacks both directly and indirectly via the media. However, less is known about the impact of this collective trauma over time. Beginning at the end of December 2006, a longitudinal study of a nationally representative sample of U.S. residents (Cohort 2, N = 1,613) examined the long-term effects of 9/11, with annual assessments administered every year for 3 years...
February 2018: Journal of Traumatic Stress
Carla Blum-Johnston, Richard B Thorpe, Chelsea Wee, Raechel Opsahl, Monica Romero, Samuel Murray, Alexander Brunelle, Quintin Blood, Rachael Wilson, Arlin B Blood, Lubo Zhang, Lawrence D Longo, William J Pearce, Sean M Wilson
Bradykinin-induced activation of the pulmonary endothelium triggers a rise in intracellular Ca2+ , which activates nitric oxide (NO)-dependent vasorelaxation. Chronic hypoxia is commonly associated with increased pulmonary vascular tone, which can cause pulmonary hypertension in responsive individuals. In the present study, we tested the hypothesis that long-term high altitude hypoxia (LTH) diminishes bradykinin-induced Ca2+ signals and inhibits eNOS, PGI2 and BKCa channels in sheep, which are moderately responsive to LTH, resulting in decreased pulmonary arterial vasorelaxation...
March 7, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Ilaria Lavagi, Stefan Krebs, Kilian Simmet, Andrea Beck, Valeri Zakhartchenko, Eckhard Wolf, Helmut Blum
Embryonic development is initially controlled by maternal RNAs and proteins stored in the oocyte, until gene products gradually generated by the embryo itself take over. Major embryonic genome activation (EGA) in bovine embryos occurs at the eight- to 16-cell stage. Morphological observations, such as size of blastomeres and distribution of microvilli, suggested heterogeneity among individual cells already at this developmental stage. To address cell heterogeneity on the transcriptome level, we performed single-cell RNA sequencing of 161 blastomeres from 14 in vitro produced bovine embryos at Day 2 (n = 6) and Day 3 (n = 8) post fertilization...
March 6, 2018: Scientific Reports
Hubert Rehrauer, Licun Wu, Walter Blum, Lazslo Pecze, Thomas Henzi, Véronique Serre-Beinier, Catherine Aquino, Bart Vrugt, Marc de Perrot, Beat Schwaller, Emanuela Felley-Bosco
Chronic exposure to intraperitoneal asbestos triggered a marked response in the mesothelium well before tumor development. Macrophages, mesothelial precursor cells, cytokines, and growth factors accumulated in the peritoneal lavage. Transcriptome profiling revealed YAP/TAZ activation in inflamed mesothelium with further activation in tumors, paralleled by increased levels of cells with nuclear YAP/TAZ. Arg1 was one of the highest upregulated genes in inflamed tissue and tumor. Inflamed tissue showed increased levels of single-nucleotide variations, with an RNA-editing signature, which were even higher in the tumor samples...
March 6, 2018: Oncogene
Scott Mintzer, Robert T Wechsler, Joanne B Rogin, Barry E Gidal, Matthias Schwab, Elinor Ben-Menachem, Mar Carreño, Patrício Soares da Silva, Joana Moreira, Yan Li, David Blum, Todd Grinnell
PURPOSE: To evaluate the effects of eslicarbazepine acetate (ESL) on lipid metabolism and to determine whether reduced statin exposure during ESL therapy has clinical consequences. SUBJECTS AND METHODS: We conducted a post-hoc analysis of pooled data for serum lipids (laboratory values) from three phase III, multicenter, randomized, double-blind, placebo-controlled trials of adjunctive ESL therapy (400, 800, or 1200 mg once daily) in patients with treatment-refractory partial-onset seizures...
February 9, 2018: Epilepsy Research
Mahyar Kashan, Mazyar Ghanaat, Andreas M Hötker, Cihan Duzgol, Alejandro Sanchez, Renzo G DiNatale, Kyle A Blum, Maria Becerra, Brandon J Manley, Jozefina Casuscelli, Michael Chiok, Jonathan A Coleman, Paul Russo, Satish K Tickoo, Oguz Akin, A Ari Hakimi
PURPOSE: To evaluate the outcomes of surgical intervention and active surveillance in patients diagnosed with cystic renal cell carcinoma at our hypothesized radiologic cutoff of >50% cystic. MATERIALS AND METHODS: We identified all patients with a pathologically confirmed cystic renal mass that fit our criteria from 2000 to 2015 (n=430). Patients with lack of CT imaging, tumors <50% cystic on imaging, multifocal tumors and prior renal cell carcinoma were excluded (n=292)...
February 26, 2018: Journal of Urology
Alina D Bayer, Andrew S Blum, Wael F Asaad, Julie Roth, Steven A Toms, Gina M Deck
While antiepileptic drugs (AEDs) provide adequate seizure control for most patients with epilepsy, ~30% continue to have seizures despite treatment with two or more AEDs.1 In addition to direct harm from seizures, poor epilepsy control correlates with higher mortality, morbidity, 2, 3 and cost to the healthcare system.4 In the subset of patients with persistent seizures despite medical management, surgical intervention and neuromodulation may be more effective. Primary care physicians and general neurologists should be aware of non-AED treatment options that are standard of care for drug- resistant epilepsy (DRE)...
March 1, 2018: Rhode Island Medical Journal
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