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Eleni Pitta, Olga Balabon, Maciej K Rogacki, Jesús Gómez, Fraser Cunningham, Jurgen Joosens, Koen Augustyns, Pieter van der Veken, Robert Bates
During the construction of bioactive molecules, regioselective alkylation of heterocyclic, N/O ambident nucleophiles is a frequently encountered synthetic transformation. In this framework, specific attention is required to unambiguously determine the structures of obtained reaction products. As part of our project on quinoloxyacetamide based antimycobacterial agents, a series of N- or O- alkylated quinolin-4-ol, 1,5-naphthyridin-4-ol and quinazolin-4-ol derivatives were prepared during the course of which we observed unexpected selectivity issues...
October 11, 2016: European Journal of Medicinal Chemistry
Xia Chen, Hua Guo, Fuxia Li, Di Fan
BACKGROUND: The present study is designed to explore the metastasis-inhibitory effect of physcion 8-O-β-glucopyranoside (PG) in human breast cancer, and the mechanisms underlying its role in tumor metastasis. METHODS: Both in vitro and in vivo studies were conducted. Cell migration and invasion were analyzed by transwell assay. The translocation of β-catenin from the nucleus to cytoplasm membrane was demonstrated by immunofluorescent staining. The expression of signaling molecules was determined by Western blot or qRT-PCR...
September 13, 2016: Pharmacological Reports: PR
Bin Tang, Yanmei Huang, Hongqin Yang, Peixiao Tang, Hui Li
As a natural dietary polyphenol, 3,4,5-tri-O-caffeoylquinic acid (3,4,5-triCQA) exhibits numerous stronger pharmacological activities than that of its analogues. Studies on interaction between 3,4,5-triCQA and protein are very helpful for understanding the mechanism of these enhanced biological functions. In this study, (1)H saturation transfer difference NMR ((1)H STD-NMR) combined with multi-spectroscopy were used to probe the interaction of 3,4,5-triCQA with human serum albumin (HSA). Both qualitative and quantitative (1)H STD-NMR indicated that 3,4,5-triCQA can specifically bind to HSA at the favored Sudlow's site II with caffeoyl groups as the main recognizable moiety...
October 17, 2016: Journal of Photochemistry and Photobiology. B, Biology
Camilo A F Salvador, Mariana R Dal Bó, Fernando H Costa, Marcia O Taipina, Eder S N Lopes, Rubens Caram
In this study, we explored the Ti-Nb-Fe system to find an optimal cost-effective composition with the lowest elastic modulus and the lowest added Nb content. Six Ti-(31-4x)Nb-(1+0.5x)Fe ingots were prepared and Nb was substituted with Fe, starting at Ti-31Nb-1.0Fe and going up to Ti-11Nb-3.5Fe (wt%). The ingots were subjected to cold rolling, recrystallization and solution treatment, followed by water-quenching (WQ), furnace cooling (FC) or step-quenching to 350°C, which caused massive formation of isothermal ω phase...
September 19, 2016: Journal of the Mechanical Behavior of Biomedical Materials
Yadvinder Malhi, Cécile A J Girardin, Gregory R Goldsmith, Christopher E Doughty, Norma Salinas, Daniel B Metcalfe, Walter Huaraca Huasco, Javier E Silva-Espejo, Jhon Del Aguilla-Pasquell, Filio Farfán Amézquita, Luiz E O C Aragão, Rossella Guerrieri, Françoise Yoko Ishida, Nur H A Bahar, William Farfan-Rios, Oliver L Phillips, Patrick Meir, Miles Silman
Why do forest productivity and biomass decline with elevation? To address this question, research to date generally has focused on correlative approaches describing changes in woody growth and biomass with elevation. We present a novel, mechanistic approach to this question by quantifying the autotrophic carbon budget in 16 forest plots along a 3300 m elevation transect in Peru. Low growth rates at high elevations appear primarily driven by low gross primary productivity (GPP), with little shift in either carbon use efficiency (CUE) or allocation of net primary productivity (NPP) between wood, fine roots and canopy...
October 21, 2016: New Phytologist
Lasse van Wijlick, René Geissen, Jessica S Hilbig, Quentin Lagadec, Pilar D Cantero, Eugen Pfeifer, Mateusz Juchimiuk, Sven Kluge, Stephan Wickert, Paula Alepuz, Joachim F Ernst
In eukaryotes, Dom34 upregulates translation by securing levels of activatable ribosomal subunits. We found that in the yeast Saccharomyces cerevisiae and the human fungal pathogen Candida albicans, Dom34 interacts genetically with Pmt1, a major isoform of protein O-mannosyltransferase. In C. albicans, lack of Dom34 exacerbated defective phenotypes of pmt1 mutants, while they were ameliorated by Dom34 overproduction that enhanced Pmt1 protein but not PMT1 transcript levels. Translational effects of Dom34 required the 5'-UTR of the PMT1 transcript, which bound recombinant Dom34 directly at a CA/AC-rich sequence and regulated in vitro translation...
October 2016: PLoS Genetics
Kerry A Geiler-Samerotte, Yuan O Zhu, Benjamin E Goulet, David W Hall, Mark L Siegal
The protein-folding chaperone Hsp90 has been proposed to buffer the phenotypic effects of mutations. The potential for Hsp90 and other putative buffers to increase robustness to mutation has had major impact on disease models, quantitative genetics, and evolutionary theory. But Hsp90 sometimes contradicts expectations for a buffer by potentiating rapid phenotypic changes that would otherwise not occur. Here, we quantify Hsp90's ability to buffer or potentiate (i.e., diminish or enhance) the effects of genetic variation on single-cell morphological features in budding yeast...
October 2016: PLoS Biology
Ersin Özaslan, Halit Karaca, Sinan Koca, Alper Sevinç, Bekir Hacioğlu, Metin Özkan, Melike Özçelik, Ayşe O Duran, İlhan Hacibekiroğlu, Yaşar Yildiz, Özgür Tanriverdi, Serkan Menekşe, Asude Aksoy, Oktay Bozkurt, Semiha Urvay, Mükremin Uysal, Hacer Demir, Aydin Çiltaş, Faysal Dane
The objectives of this study were to compare progression-free survival (PFS) with somatostatin analog (SSA) versus chemotherapy (CTx) in first-line therapy and to determine the patient group in which these treatments were more effective in neuroendocrine tumors (NETs) with a Ki-67 index of 20% or less. Patients who received SSA or CTx and had unresectable locally advanced and metastatic NETs with a Ki-67 index of 20% or less were retrospectively selected from 13 centers in the Turkish database between 2000 and 2015...
October 20, 2016: Anti-cancer Drugs
Michael C Sklar, Karen Burns, Nuttapol Rittayamai, Ashley Lanys, Michela Rauseo, Lu Chen, Martin Dres, Guang-Qiang Chen, Ewan C Goligher, Neill Kj Adhikari, Laurent Brochard, Jan O Friedrich
Introduction Spontaneous breathing trials (SBTs) are designed to simulate conditions following extubation and it is essential to understand the physiological impact of different methods. We conducted a systematic review and pooled measures reflecting patient respiratory effort among studies comparing SBT methods in a meta-analysis. Methods We searched Medline, EMBASE, and Web of Science from inception to January 2016 to identify randomized and non-randomized clinical trials reporting physiological measurements of respiratory effort (pressure-time product, PTP) or work of breathing during at least 2 SBT techniques...
October 21, 2016: American Journal of Respiratory and Critical Care Medicine
Allegra T Aron, Morten O Loehr, Jana Bogena, Christopher J Chang
Iron is essential for sustaining life, as its ability to cycle between multiple oxidation states is critical for catalyzing chemical transformations in biological systems. However, without proper regulation, this same redox capacity can trigger oxidative stress events that contribute to aging along with diseases ranging from cancer to cardiovascular and neurodegenerative disorders. Despite its importance, methods for monitoring biological iron bound weakly to cellular ligands-the labile iron pool-to generate a response that preserves spatial and temporal information remain limited, owing to the potent fluorescence quenching ability of iron...
October 21, 2016: Journal of the American Chemical Society
Xiangyi Zhang, Gavin O Jones, James L Hedrick, Robert M Waymouth
Ring-opening polymerization of lactones is a versatile approach to generate well-defined functional polyesters. Typical ring-opening catalysts are subject to a trade-off between rate and selectivity. Here we describe an effective catalytic system combining alkoxides with thioureas that catalyses rapid and selective ring-opening polymerizations. Deprotonation of thioureas by sodium, potassium or imidazolium alkoxides generates a hydrogen-bonded alcohol adduct of the thiourea anion (thioimidate). The ring-opening polymerization of L-lactide mediated by these alcohol-bonded thioimidates yields highly isotactic polylactide with fast kinetics and living polymerization behaviour, as evidenced by narrow molecular weight distributions (Mw/Mn < 1...
November 2016: Nature Chemistry
Jorge A Gonzalez, O Maduka Ogba, Gregory F Morehouse, Nicholas Rosson, Kendall N Houk, Andrew G Leach, Paul H-Y Cheong, Martin D Burke, Guy C Lloyd-Jones
MIDA boronates (N-methylimidodiacetic boronic acid esters) serve as an increasingly general platform for small-molecule construction based on building blocks, largely because of the dramatic and general rate differences with which they are hydrolysed under various basic conditions. Yet the mechanistic underpinnings of these rate differences have remained unclear, which has hindered efforts to address the current limitations of this chemistry. Here we show that there are two distinct mechanisms for this hydrolysis: one is base mediated and the other neutral...
November 2016: Nature Chemistry
Jaclyn K Schwartz, Roger O Smith
OBJECTIVE: Many people with chronic health conditions fail to take their medications as prescribed, resulting in declines in health and function. The purpose of this study was to perform a Phase I feasibility study to understand whether an integrated occupational therapy intervention could help people with chronic health conditions improve their adherence to medications. METHOD: Using a small-N design, we report single-subject analyses of the medication adherence of 11 participants before and after either an occupational therapy intervention or a standard care intervention...
November 2016: American Journal of Occupational Therapy: Official Publication of the American Occupational Therapy Association
Alexander A Theologis, Gregory M Mundis, Stacie Nguyen, David O Okonkwo, Praveen V Mummaneni, Justin S Smith, Christopher I Shaffrey, Richard Fessler, Shay Bess, Frank Schwab, Bassel G Diebo, Douglas Burton, Robert Hart, Vedat Deviren, Christopher Ames
OBJECTIVE The aim of this study was to evaluate the utility of supplementing long thoracolumbar posterior instrumented fusion (posterior spinal fusion, PSF) with lateral interbody fusion (LIF) of the lumbar/thoracolumbar coronal curve apex in adult spinal deformity (ASD). METHODS Two multicenter databases were evaluated. Adults who had undergone multilevel LIF of the coronal curve apex in addition to PSF with L5-S1 interbody fusion (LS+Apex group) were matched by number of posterior levels fused with patients who had undergone PSF with L5-S1 interbody fusion without LIF (LS-Only group)...
October 21, 2016: Journal of Neurosurgery. Spine
Michael O Childress, José A Ramos-Vara, Audrey Ruple
OBJECTIVE To determine the effect of prednisone omission from a multidrug chemotherapy protocol on outcome in dogs with peripheral nodal lymphomas. DESIGN Single-center, nonblinded, parallel-group, randomized, controlled trial. ANIMALS 40 client-owned dogs with a histopathologically confirmed diagnosis of peripheral nodal lymphoma and an expected survival time of > 4 weeks with treatment. PROCEDURES Treatment consisted of a combination of L-asparaginase, cyclophosphamide, doxorubicin, vincristine, and prednisone (L-CHOP) or an identical protocol except for the omission of prednisone (L-CHO)...
November 1, 2016: Journal of the American Veterinary Medical Association
Jasmine A Mena, Gifty G Ampadu, James O Prochaska
BACKGROUND: Tobacco use remains the leading cause of preventable disease and death. Most smokers are not motivated to quit; however, most smoking cessation interventions are designed for smokers who are ready to take action. OBJECTIVES: The aim of the present study was to describe participant engagement and satisfaction with telephonic smoking cessation coaching with a population of smokers at different stages of readiness to quit. METHODS: Qualitative description was used to capture the experiences of 62 individuals who participated in telephonic smoking cessation coaching using semistructured interviews...
October 21, 2016: Substance Use & Misuse
Brent M Egan, Bo Kai, C Shaun Wagner, Douglas O Fleming, Joseph H Henderson, Archie H Chandler, Angelo Sinopoli
Apparent treatment-resistant hypertension (aTRH) may confound the reported relationship between low blood pressure (BP) and increased cardiovascular disease (CVD) in treated hypertensive patients. Incident CVD was assessed in treated hypertensive patients with and without aTRH (BP ≥140 and/or ≥90 mm Hg on ≥3 medications or <140/<90 mm Hg on ≥4 BP medications) at three BP levels: 1: <120 and/or <70 mm Hg and <140/<90 mm Hg; 2: 120-139/70-89 mm Hg; and 3: ≥140 and/or ≥90 mm Hg. Electronic health data were matched to emergency and hospital claims for incident CVD in 118 356 treated hypertensive patients...
October 21, 2016: Journal of Clinical Hypertension
Chen Luo, Lu-Ting Yu, Meng-Qi Yang, Xiang Li, Zhi-Yuan Zhang, Martin O Alfred, Jun-Li Liu, Min Wang
Regenerating genes (Reg) have been found during the search for factors involved in pancreatic islet regeneration. Our recent study discovered that pancreatic β-cell-specific overexpression of Reg3β protects against streptozotocin (Stz) -induced diabetes in mice. To investigate its potential roles in the treatment of diabetes, we produced a recombinant Reg3β protein and provided evidence that it is active in promoting islet β-cell survival against Stz- triggered cell death. Though ineffective in alleviating preexisting diabetes, pretreatment of recombinant Reg3β was capable of minimizing the Stz-induced hyperglycemia and weight loss, by preserving serum and pancreatic insulin levels, and islet β-cell mass...
October 21, 2016: Scientific Reports
Deven P Estes, Georges Siddiqi, Florian Allouche, Kirill V Kovtunov, Olga E Safonova, Alexander L Trigub, Igor V Koptyug, Christophe Copéret
The activation and conversion of hydrocarbons is one of the most important challenges in chemistry. Transition-metal ions (V, Cr, Fe, Co…) isolated on silica surfaces are known to catalyze these processes. The mechanisms of these processes are currently unknown but are thought to involve C-H activation as the rate determining step. Here, we synthesize well-defined Co(II) ions on a silica surface using a metal siloxide precursor followed by thermal treatment under vacuum at 500°C. We show that these isolated Co(II) sites are catalysts for a number of hydrocarbon conversion reactions, such as the dehydrogenation of propane, the hydrogenation of propene, and the trimerization of terminal alkynes...
October 21, 2016: Journal of the American Chemical Society
Daniel B Schwab, Armin P Moczek
The elaboration of exaggerated, sexually selected weapons and ornaments often comes at a cost to other traits. For instance, by sustaining the growth of an exaggerated weapon during development, shared and limited resources such as morphogens, growth factors, and nutrients may become depleted and limit the size to which other structures can grow. Such interactions are characteristic of resource allocation trade-offs, which can constrain the production of phenotypic variation and bias evolutionary trajectories...
October 21, 2016: Journal of Experimental Zoology. Part A, Ecological Genetics and Physiology
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