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Tolerance Reduction

Silvania da Silva Teixeira, Carly Filgueira, Douglas H Sieglaff, Cindy Benod, Rosa Villagomez, Laurie J Minze, Aijun Zhang, Paul Webb, Maria Tereza Nunes
AIM: Thyroid hormones regulate metabolic response. While triiodothyronine (T3) is usually considered to be the active form of thyroid hormone, one form of diiodothyronine (3,5-T2) exerts T3-like effects on energy consumption and lipid metabolism. 3,5-T2 also improves glucose tolerance in rats and 3,5-T2 levels correlate with fasting glucose in humans. Presently, however, little is known about mechanisms of 3,5-T2 effects on glucose metabolism. Here, we set out to compare effects of T3, 3,5-T2 and another form of T2 (3,3-T2) in a mouse model of diet induced obesity and determined effects of T3 and 3,5-T2 on markers of classical insulin sensitization to understand how diiodothyronines influence blood glucose...
October 22, 2016: Acta Physiologica
Mathias Kranz, Bernhard Sattler, Solveig Tiepolt, Stephan Wilke, Winnie Deuther-Conrad, Cornelius K Donat, Steffen Fischer, Marianne Patt, Andreas Schildan, Jörg Patt, René Smits, Alexander Hoepping, Jörg Steinbach, Osama Sabri, Peter Brust
BACKGROUND: Both enantiomers of [(18)F]flubatine are new radioligands for neuroimaging of α4β2 nicotinic acetylcholine receptors with positron emission tomography (PET) exhibiting promising pharmacokinetics which makes them attractive for different clinical questions. In a previous preclinical study, the main advantage of (+)-[(18)F]flubatine compared to (-)-[(18)F]flubatine was its higher binding affinity suggesting that (+)-[(18)F]flubatine might be able to detect also slight reductions of α4β2 nAChRs and could be more sensitive than (-)-[(18)F]flubatine in early stages of Alzheimer's disease...
December 2016: EJNMMI Physics
Tommaso Michele Moles, Antonio Pompeiano, Thais Huarancca Reyes, Andrea Scartazza, Lorenzo Guglielminetti
Landraces represent an important part of the biodiversity well-adapted under limiting environmental conditions. We investigated the response of two Southern Italy tomato landraces, the well-known San Marzano (our commercial standard) and a local accession called "Ciettaicale", to different levels of sodium chloride in water irrigation (from 0 up to 600 mM) for a short-time exposure (one week). The combination of the chlorophyll a fluorescence and gas exchange analyses suggested that Ciettaicale maintained a higher efficiency of photosystem II (PSII) photochemistry and CO2 utilization at high salinity concentrations than San Marzano...
October 12, 2016: Plant Physiology and Biochemistry: PPB
Gvido Cebers, Robert C Alexander, Samantha Budd Haeberlein, David Han, Ronald Goldwater, Larry Ereshefsky, Tina Olsson, Naidong Ye, Laura Rosen, Muir Russell, Justine Maltby, Susanna Eketjäll, Alan R Kugler
AZD3293 (LY3314814) is a promising new potentially disease-modifying BACE1 (β-secretase) inhibitor in Phase III clinical development for the treatment of Alzheimer's disease. Reported here are the first two Phase I studies: (1) a single ascending dose study evaluating doses of 1-750 mg with a food-effect component (n = 72), and (2) a 2-week multiple ascending dose study evaluating doses of 15 or 50 mg once daily (QD) or 70 mg once weekly (QW) in elderly subjects (Part 1, n = 31), and 15, 50, or 150 mg QD in patients with mild to moderate Alzheimer's disease (Part 2, n = 16)...
October 19, 2016: Journal of Alzheimer's Disease: JAD
Yeoree Yang, Jeong Ah Shin, Hae Kyung Yang, Seung Hwan Lee, Seung Hyun Ko, Yu Bae Ahn, Kun Ho Yoon, Jae Hyoung Cho
BACKGROUND: There were a limited number of studies about β-cell function after insulin initiation in patients exposed to long durations of sulfonylurea treatment. In this study, we aimed to evaluate the recovery of β-cell function and the efficacy of concurrent sulfonylurea use after the start of long-acting insulin. METHODS: In this randomized controlled study, patients with type 2 diabetes mellitus (T2DM), receiving sulfonylurea for at least 2 years with glycosylated hemoglobin (HbA1c) >7%, were randomly assigned to two groups: sulfonylurea maintenance (SM) and sulfonylurea reduction (SR)...
October 11, 2016: Diabetes & Metabolism Journal
Diego M Almeida, Glenn B Gregorio, M Margarida Oliveira, Nelson J M Saibo
This manuscript reports the identification and characterization of five transcription factors binding to the promoter of OsNHX1 in a salt stress tolerant rice genotype (Hasawi). Although NHX1 encoding genes are known to be highly regulated at the transcription level by different abiotic stresses, namely salt and drought stress, until now only one transcription factor (TF) binding to its promoter has been reported. In order to unveil the TFs regulating NHX1 gene expression, which is known to be highly induced under salt stress, we have used a Y1H system to screen a salt induced rice cDNA expression library from Hasawi...
October 20, 2016: Plant Molecular Biology
Yaeko Fukushima, Satoshi Kurose, Hiromi Shinno, Ha Cao Thi Thu, Nana Takao, Hiromi Tsutsumi, Takaaki Hasegawa, Toshiaki Nakajima, Yutaka Kimura
BACKGROUND: Irisin is a myokine implicated in lipid and glucose metabolism. The objective of this study is to examine the effect of a body weight reduction on the serum irisin level and physical indicators in obese Japanese patients without diabetes. METHODS: The subjects were 22 patients (male/female, 5/17; age, 46.1±16.0 years; body mass index [BMI], 36.9±5.0 kg/m(2)) who completed a 6-month body weight reduction program at our clinic. The program included diet, exercise therapy and cognitive behavioral therapy...
October 2016: Diabetes & Metabolism Journal
G Guidi, N Maffei, B Meduri, E D'Angelo, G M Mistretta, P Ceroni, A Ciarmatori, A Bernabei, S Maggi, M Cardinali, V E Morabito, F Rosica, S Malara, A Savini, G Orlandi, C D'Ugo, F Bunkheila, M Bono, S Lappi, C Blasi, F Lohr, T Costi
PURPOSE: To predict patients who would benefit from adaptive radiotherapy (ART) and re-planning intervention based on machine learning from anatomical and dosimetric variations in a retrospective dataset. MATERIALS AND METHODS: 90 patients (pts) treated for head-neck cancer (H&N) formed a multicenter data-set. 41 H&N pts (45.6%) were considered for learning; 49 pts (54.4%) were used to test the tool. A homemade machine-learning classifier was developed to analyze volume and dose variations of parotid glands (PG)...
October 17, 2016: Physica Medica: PM
Wojciech Kosmala, Aleksandra Rojek, Monika Przewlocka-Kosmala, Leah Wright, Andrzej Mysiak, Thomas H Marwick
BACKGROUND: Impaired functional capacity is a hallmark of patients with heart failure with preserved ejection fraction (HFpEF). Despite the association of HFpEF with reduced myocardial compliance attributed to fibrosis, spironolactone has not been shown to alter outcomes-perhaps reflecting the heterogeneity of underlying pathological mechanisms. OBJECTIVES: The authors sought to identify improvement in exercise capacity with spironolactone in the subset of patients with HFpEF with exercise-induced increase in ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e') reflecting elevation of left ventricular (LV) filling pressure...
October 25, 2016: Journal of the American College of Cardiology
Yongseok Yoo, Woori Kim
Neural systems are inherently noisy. One well-studied example of a noise reduction mechanism in the brain is the population code, where representing a variable with multiple neurons allows the encoded variable to be recovered with fewer errors. Studies have assumed ideal observer models for decoding population codes, and the manner in which information in the neural population can be retrieved remains elusive. This letter addresses a mechanism by which realistic neural circuits can recover encoded variables...
October 20, 2016: Neural Computation
Gianna Sepede, Giuseppe Di Iorio, Maria Chiara Spano, Marco Lorusso, Fabiola Sarchione, Rita Santacroce, Rosa Maria Salerno, Massimo Di Giannantonio
BACKGROUND: Treatment-resistant schizophrenia (TRS) is a condition characterized by intense symptom severity and poor response to different antipsychotic agents. The first therapeutic option in TRS is clozapine, but often high/medium doses are not tolerated. Adding an oral antipsychotic to low doses of clozapine is a promising strategy in the management of TRS. On the contrary, there are few data on combined clozapine/long-acting injectable (LAI) medications, and none on clozapine/LAI-aripiprazole...
October 18, 2016: Clinical Neuropharmacology
Rüdiger Hardeland
Dynamic aspects of melatonin's actions merit increasing future attention. This concerns particularly entirely different effects in senescent, weakened oscillators and in dysregulated oscillators of cancer cells that may be epigenetically blocked. This is especially obvious in the case of sirtuin 1 (SIRT1) which is upregulated by melatonin in aged tissues, but strongly downregulated in several cancer cells. These findings are not at all controversial, but are explained on the basis of divergent changes in weakened and dysregulated oscillators...
October 20, 2016: Journal of Pineal Research
Suchithra Padmajan Sasikala, Kai Huang, Baptiste Giroire, Prem Prabhakaran, Lucile Henry, Alain Pénicaud, Philippe Poulin, Cyril Aymonier
We report the exfoliation of graphite and simultaneous N doping of graphene by two methods; by supercritical ammonia treatment and by liquid phase exfoliation with NH4OH. While the supercritical ammonia allowed N doping at a level of 6.4 at.% in 2 h, the liquid phase exfoliation with NH4OH allowed N doping at a level of 2.7at.% in 6 h. The N doped graphene obtained via supercritical ammonia route were few layers (<5), showed large lateral flake size (~8µm), low defect density (ID/IG<0.6) in spite of their high level of N doping...
October 20, 2016: ACS Applied Materials & Interfaces
Chuanguang Yao, Hongxin Song, Ying Wan, Kefeng Ma, Chenyu Zheng, Hongda Cui, Peng Xin, Xubo Ji, Sheng-Yuan Deng
A porphyrin-based electro-photodynamic imaging system was fabricated for monitoring the concentration of oxygen. Distinct from the electrochemiluminescent (ECL) inability of numerous organic species in aqueous solutions, a strong and stable red irradiation at 634 nm could be stimulated electrochemically on zinc(II) meso-tetra(4-carboxyphenyl) porphine (ZnTCPP)/tetraoctylammonium bromide (TOAB) in the physiological condition. In terms of in situ electron paramagnetic resonance and ECL spectroscopies, the nature of ECL was thoroughly investigated, being exactly the chemiluminescence from singlet oxygen (1O2) produced during the successive electro-reduction of ZnTCPP...
October 20, 2016: ACS Applied Materials & Interfaces
Yingxiao Cai, Andreas Benischke, Paul Knochel, Corinne Gosmini
A simple and efficient protocol for the direct reductive cross-coupling between alkenyl and benzyl halides using a Co/Mn system has been developed. This reaction proceeds smoothly in the presence of [CoBr2(PPh3)2] as catalyst, with NaI as additive in acetonitrile with a broad scope of functionalized alkenyl and benzyl halides. Different functional groups are tolerated on both coupling partners, thus, significantly extending the general scope of transition-metal-catalyzed benzylation of alkenyl halides. Moderate to excellent yields were obtained...
October 20, 2016: Chemistry: a European Journal
Hemant Gujar, Subba Reddy Palli
To begin studies on reproduction in common bed bug, Cimex lectularius, we identified three genes coding for vitellogenin (Vg, a protein required for the reproductive success of insects) and studied their hormonal regulation. RNA interference studied showed that expression of Vg3 gene in the adult females is a prerequisite for successful completion of embryogenesis in the eggs laid by them. Juvenile hormone (JH) receptor, Methoprene-tolerant (Met), steroid receptor coactivator (SRC) and GATAa but not ecdysone receptor (EcR) or its partner, ultraspiracle (USP) are required for expression of Vg genes...
October 20, 2016: Scientific Reports
Julienne K Muenzner, Bernhard Biersack, Alexander Albrecht, Tobias Rehm, Ulrike Lacher, Wolfgang Milius, Angela Casini, Jing-Jing Zhang, Ingo Ott, Viktor Brabec, Olga Stuchlikova, Ion C Andronache, Detlef Schuppan, Leonard Kaps, Rainer Schobert
Four gold(I) carbene complexes featuring 4-ferrocenyl substituted imidazol-2-ylidene ligands were investigated for antiproliferative and antivascular properties. They were active against a panel of seven cancer cell lines, including multidrug-resistant ones, with low micromolar or nanomolar IC50 (72 h) values, according to their lipophilicity and cellular uptake. The delocalised lipophilic cationic complexes 8 and 10 acted by increasing the reactive oxygen species in two ways: via a genuine ferrocene effect and by inhibiting the thioredoxin reductase...
October 20, 2016: Chemistry: a European Journal
Jitsuo Higaki, Issei Komuro, Kosuke Shiki, Ganghyuck Lee, Atsushi Taniguchi, Hiroshi Ikeda, Daisuke Kuroki, Seiichiro Nishimura, Toshio Ogihara
The efficacy and safety of telmisartan 80 mg/amlodipine 5 mg plus hydrochlorothiazide 12.5 mg (T80/A5/H12.5) was examined for its ability to treat hypertension in Japanese patients whose hypertension is uncontrolled with telmisartan 80 mg/amlodipine 5 mg (T80/A5). Patients aged ⩾20 years who had essential hypertension despite taking two or three antihypertensive drugs entered a 6-week run-in period on T80/A5. Patients whose hypertension remained uncontrolled were randomly assigned to either the T80/A5/H12...
October 20, 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Omar S Aljitawi, Soumen Paul, Avishek Ganguly, Tara L Lin, Sid Ganguly, George Vielhauer, Maegan L Capitano, Amy Cantelina, Brea Lipe, Jonathan D Mahnken, Amanda Wise, Abigale Berry, Anurag K Singh, Leyla Shune, Christopher Lominska, Sunil Abhyankar, Dennis Allin, Mary Laughlin, Joseph P McGuirk, Hal E Broxmeyer
Umbilical cord blood (UCB) engraftment is in part limited by graft cell dose, generally one log less than that of bone marrow (BM)/peripheral blood (PB) cell grafts. Strategies toward increasing hematopoietic stem/progenitor cell (HSPC) homing to BM have been assessed in order to improve UCB engraftment. Despite recent progress, a complete understanding of how HSPC homing and engraftment are regulated is still elusive. We provide evidence that blocking erythropoietin (EPO)-EPO receptor (R) signaling promotes homing to BM and early engraftment of UCB CD34(+) cells...
October 19, 2016: Blood
Maxime Cailleret, Steven Jansen, Elisabeth M R Robert, Lucía Desoto, Tuomas Aakala, Joseph A Antos, Barbara Beikircher, Christof Bigler, Harald Bugmann, Marco Caccianiga, Vojtěch Čada, J Julio Camarero, Paolo Cherubini, Hervé Cochard, Marie R Coyea, Katarina Čufar, Adrian J Das, Hendrik Davi, Sylvain Delzon, Michael Dorman, Guillermo Gea-Izquierdo, Sten Gillner, Laurel J Haavik, Henrik Hartmann, Ana-Maria Hereş, Kevin R Hultine, Pavel Janda, Jeffrey M Kane, Vyacheslav I Kharuk, Thomas Kitzberger, Tamir Klein, Koen Kramer, Frederic Lens, Tom Levanic, Juan Carlos Linares Calderon, Francisco Lloret, Raquel Lobo-Do-Vale, Fabio Lombardi, Rosana López Rodríguez, Harri Mäkinen, Stefan Mayr, Ilona Mészáros, Juha M Metsaranta, Francesco Minunno, Walter Oberhuber, Andreas Papadopoulos, Mikko Peltoniemi, Any Mary Petritan, Brigitte Rohner, Gabriel Sangüesa-Barreda, Dimitrios Sarris, Jeremy M Smith, Amanda B Stan, Frank Sterck, Dejan B Stojanović, Maria Laura Suarez, Miroslav Svoboda, Roberto Tognetti, José M Torres-Ruiz, Volodymyr Trotsiuk, Ricardo Villalba, Floor Vodde, Alana R Westwood, Peter H Wyckoff, Nikolay Zafirov, Jordi Martínez-Vilalta
Tree mortality is a key factor influencing forest functions and dynamics, but our understanding of the mechanisms leading to mortality and the associated changes in tree growth rates are still limited. We compiled a new pan-continental tree-ring width database from sites where both dead and living trees were sampled (2,970 dead and 4,224 living trees from 190 sites, including 36 species), and compared early and recent growth rates between trees that died and those that survived a given mortality event. We observed a decrease in radial growth before death in ca...
October 19, 2016: Global Change Biology
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