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Activity tolerance

Andreas Porodko, Ana Cirnski, Drazen Petrov, Teresa Raab, Melanie Paireder, Bettina Mayer, Daniel Maresch, Lisa Nika, Martin L Biniossek, Patrick Gallois, Oliver Schilling, Chris Oostenbrink, Marko Novinec, Lukas Mach
The genome of the model plant Arabidopsis thaliana encodes three paralogues of the papainlike cysteine proteinase cathepsin B (AtCathB1, AtCathB2 and AtCathB3), whose individual functions are still largely unknown. Here we show that a mutated splice site causes severe truncations of the AtCathB1 polypeptide, rendering it catalytically incompetent. By contrast, AtCathB2 and AtCathB3 are effective proteases which display comparable hydrolytic properties and share most of their substrate specificities. Site-directed mutagenesis experiments demonstrated that a single amino acid substitution (Gly336→Glu) is sufficient to confer AtCathB2 with the capacity to tolerate arginine in its specificity-determining S2 subsite, which is otherwise a hallmark of AtCathB3-mediated cleavages...
June 1, 2018: Biological Chemistry
Khanh Nguyen, Carlos Cuellar, Prabhjot Sandy Mavi, Danika LeDuc, Gary Bañuelos, Monika Sommerhalter
Poplar hybrids can be used for selenium (Se) and boron (B) phytoremediation under saline conditions. The phenolic antioxidant stress response of two salt and B tolerant poplar hybrids of parentage Populus trichocarpa x nigra x deltoides was studied using high performance liquid chromatography (HPLC) and absorption based assays to determine the antioxidant capacity, total phenolic content, hydroxycinnamic acid levels, and the enzyme activity of L-phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO), phenol peroxidase (POD), and laccase...
June 20, 2018: Journal of Agricultural and Food Chemistry
Sena Kim, Yeonsoo Joe, Se-Ung Park, Sun Oh Jeong, Jin-Kyung Kim, Seong Hoon Park, Hyun-Ock Pae, Young-Joon Surh, Jaekyoon Shin, Hun Taeg Chung
Endotoxin tolerance develops in the late phase of sepsis to protect cells from an early hyperinflammatory response. Nonetheless, because it induces an immunosuppressive environment, patients with sepsis in its late phase are affected by secondary infections, particularly bacterial pneumonia. Here, we showed that induction of endoplasmic reticulum (ER) stress leads to activation of glycogen synthase kinase 3β (GSK-3β) and X-box-binding protein 1 (XBP-1) in an inositol-requiring enzyme 1α (IRE1α)-mediated manner, which in turn restores the inflammatory response in endotoxin-tolerant macrophages...
June 20, 2018: Journal of Leukocyte Biology
Elisabeth Maurer, Caroline Hörtnagl, Michaela Lackner, Denise Grässle, Verena Naschberger, Patrizia Moser, Esther Segal, Margarita Semis, Cornelia Lass-Flörl, Ulrike Binder
Mucorales can cause cutaneous to deep-seated infections, mainly in the immunocompromised host, resulting in high mortality rates due to late and inefficient treatment. In this study, Galleria mellonella larvae were evaluated as a heterologous invertebrate host to study pathogenicity of clinically relevant mucormycetes (Rhizopus spp., Rhizomucor spp., Lichtheimia spp., Mucor spp.). All tested species were able to infect G. mellonella larvae. Virulence potential was species-specific and correlated to clinical relevance...
June 19, 2018: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Y L Long, F Qiao, X F Jiang, H Q Cong, M L Sun, Z J Xu
Synthetic polyploids are key breeding materials for watermelon. Compared with diploid watermelon, the tetraploid watermelon often exhibit wide phenotypic differences and differential gene expression. Digital gene expression (DGE) profile technique was performed in this study to present gene expression patterns in an autotetraploid and its progenitor diploid watermelon, and deferentially expressed genes (DEGs) related to the abiotic and biotic stress were also addressed. Altogether, 4,985 DEGs were obtained in the autotetraploid against its progenitor diploid, and 66...
June 14, 2018: Brazilian Journal of Biology, Revista Brasleira de Biologia
Mario Gennaro Mazza, Aurora Rossetti, Eugenia Rossana Botti, Massimo Clerici
RATIONALE: Vortioxetine is a new multimodal antidepressant approved by the Food and Drug Administration for the treatment of Major Depressive Disorder and recently introduced in Europe. While antidepressant properties of vortioxetine and its tolerability have been demonstrated by preclinical and clinical studies data on the safety of vortioxetine after overdose are still lacking. PATIENT CONCERNS: A 50-year-old Caucasian man presenting a severe depressive episode that in a suicide attempt he took vortioxetine at 250 mg...
June 2018: Medicine (Baltimore)
Tian-Long Zhai, Cuijuan Xuan, Jincheng Xu, Li Ban, Zhiming Cheng, Shaolei Wang, Deli Wang, Bien Tan, Chun Zhang
Highly porous carbonaceous nonprecious metal catalysts for oxygen reduction reaction are prepared by carbonization of low-cost metalloporphyrin-based hypercrosslinked polymers (MPH-X). With high surface area (2768 m2 g-1), hierarchical porous structure and high metal loading (9.97 wt %), the obtained hyperporous carbon MPH-Fe/C catalyst exhibits high oxygen reduction reaction (ORR) activity with a half-wave potential (0.816 V) that is comparable to the 0.819 V of commercial Pt/C. Stability tests reveal that MPH-Fe/C also exhibits outstanding long-term durability and methanol-tolerance...
June 20, 2018: Chemistry, An Asian Journal
Chunhong Chen, Xuefeng Li, Deng Jiang, Zhe Wang, Yong Wang
To realize the asymmetry for the hollow carbonaceous nanostructures remains to be a great challenge, especially when biomass is chosen as the carbon resource via hydrothermal carbonization (HTC). Herein, a simple and straightforward solvent induced buckling strategy is demonstrated for the synthesis of asymmetric spherical and bowllike carbonaceous nanomaterials. The formation of the bowllike morphology was attributed to the buckling of the spherical shells induced by the dissolution of the oligomers. The bowllike particles made by this solvent-driven approach demonstrated a well-controlled morphology and a uniform particle size of ~360 nm...
June 19, 2018: ChemSusChem
Kashinath Dixit, Dinesh Venkata Kamath, Krishnaraju Venkata Alluri, Barbara A Davis
AIMS: LI85008F is a novel, proprietary herbal blend containing extracts of Moringa oleifera and Murraya koeingii leaves plus extract of Curcuma longa root. Weight loss efficacy of LI85008F was first demonstrated in obese adults and has now been re-evaluated in healthy overweight adults via a 16-week randomized, double-blind, placebo-controlled clinical study. MATERIAL & METHODS: One hundred and forty overweight participants (Body mass index 27 to 29.9 kg/m2 , 29...
June 19, 2018: Diabetes, Obesity & Metabolism
James E Frampton
Lisdexamfetamine dimesylate (lisdexamfetamine; Elvanse® ; Tyvense® ), an orally-active dexamfetamine prodrug, is indicated in the EU for the treatment of attention-deficit hyperactivity disorder (ADHD) in children aged ≥ 6 years (including adolescents) when the response to previous methylphenidate (MPH) treatment is clinically inadequate. The original approval of the drug was based on the results of phase III trials in children and adolescents with ADHD who had an inadequate response to previous pharmacotherapy (e...
June 19, 2018: Drugs
Yanyu Wu, José M Veleta, Diya Tang, Alex D Price, Cristian E Botez, Dino Villagrán
Herein, we report a crystalline CoTcPP-based [TcPP = the anion of meso-tetra(4-carboxyphenyl)porphyrin] polymeric system, 1, as a hydrogen evolution reaction (HER) electrocatalyst in acidic aqueous media. The material was characterized by powder X-ray diffraction (p-XRD), Fourier transform infrared (FT-IR) spectroscopy, and energy dispersive X-ray (EDX) analysis and its morphology was probed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Polymer 1 shows a surface area of 441...
June 20, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
Patricia A Walicke, Franz Hefti, Roxanne Bales, Shiao-Ping Lu, Jon L Ruckle, Mark T Brown, Christine R West, David L Shelton
Introduction: The neurotrophin nerve growth factor has a demonstrated role in pain transduction and pathophysiology. Objectives: Two randomized, double-blind, placebo-controlled, phase 1 studies were conducted to evaluate safety, tolerability, and analgesic efficacy of single doses of tanezumab, a humanized anti-nerve growth factor monoclonal antibody, in chronic or acute pain. Methods: In the first study (CL001), patients with moderate to severe pain from osteoarthritis (OA) of the knee received a single intravenous infusion of tanezumab (3-1000 μg/kg) or placebo in a dose-escalation (part 1; N = 42) or parallel-arm (part 2; N = 79) study design...
May 2018: Pain Reports (Baltimore, Md.)
Darius K L Aw, Hao-Yun Yap, Luke H T Tay, Kiang-Hiong Tay, Tze-Tec Chong
Introduction: In general, arteriovenous malformations (AVMs) are extremely rare, with an incidence of only 1 in 100,000. They are rarer still in the hands and present variably with bleeding, heaviness, a pulsatile mass, pain, ulceration, or necrosis. Report: The case of a 25 year old man with a rapidly bleeding right thumb AVM is presented. Bleeding was torrential and life threatening within a matter of seconds. He had previously undergone surgical ligation and embolisation twice at another centre, without success...
2018: EJVES Short Reports
Tadashi Yokoyama, Akihiko Ohta, Satoshi Motoya, Masakazu Takazoe, Toshitaka Yajima, Masataka Date, Masahiro Nii, Péter Nagy, Yasuo Suzuki, Toshifumi Hibi
Background: US and European guidelines recommend budesonide for the treatment of mild-to-moderate active ileocolic Crohn's disease (CD). However, budesonide has not been approved, and mesalazine is widely used as first-line treatment in Japan. The objective of this study was to evaluate the efficacy and safety of budesonide in patients with mild-to-moderate active CD in Japan. Methods: In this phase 3 noninferiority study (NCT01514240), 112 patients with a baseline Crohn's Disease Activity Index (CDAI) score of 180-400 were randomized to budesonide or mesalazine for 8 weeks...
March 2018: Inflammatory Intestinal Diseases
Abdolreza Hassanzade, Ali Mandegary, Elham Sharif, Rokhsana Rasooli, Reza Mohammadnejad, Yaser Masoumi-Ardekani
Objectives: Combination chemotherapy is a rational strategy to increase patient response and tolerability and to decrease adverse effects and drug resistance. Recently, the use of non-steroidal anti-inflammatory drugs (NSAIDs) has been reported to be associated with reduction in occurrence of a variety of cancers including lung cancer. On the other hand, growing evidences suggest that deuterium-enriched water (DEW, D2O) and deuterium-depleted water (DDW) play a role both in treatment and prevention of cancers...
May 2018: Iranian Journal of Basic Medical Sciences
Rinse Jaarsma, Albertus H de Boer
Potato is an important cultivated crop species and since it is moderately salt sensitive there is a need to develop more salt tolerant cultivars. A high activity of Na+ transport across the tonoplast in exchange for H+ is essential to reduce Na+ toxicity. The proton motive force (PMF) generated by the V-H+ -ATPase and the V-H+ -PPase energizes the Na+ (K+ )/H+ antiport. We compared the activity, gene expression, and protein levels of the vacuolar proton pumps and the Na+ /H+ antiporters in two potato cultivars ( Solanum tuberosum ) contrasting in their salt tolerance (cv...
2018: Frontiers in Plant Science
Mindy S Lo
The pathophysiology of systemic lupus erythematosus (SLE) has been intensely studied but remains incompletely defined. Currently, multiple mechanisms are known to contribute to the development of SLE. These include inadequate clearance of apoptotic debris, aberrant presentation of self nucleic antigens, loss of tolerance, and inappropriate activation of T and B cells. Genetic, hormonal, and environmental influences are also known to play a role. The study of lupus in children, in whom there is presumed to be greater genetic influence, has led to new understandings that are applicable to SLE pathophysiology as a whole...
2018: Frontiers in Immunology
Bassam Janji, Guy Berchem, Salem Chouaib
Cancer cells evolve in the tumor microenvironment, which is now well established as an integral part of the tumor and a determinant player in cancer cell adaptation and resistance to anti-cancer therapies. Despite the remarkable and fairly rapid progress over the past two decades regarding our understanding of the role of the tumor microenvironment in cancer development, its precise contribution to cancer resistance is still fragmented. This is mainly related to the complexity of the "tumor ecosystem" and the diversity of the stromal cell types that constitute the tumor microenvironment...
2018: Frontiers in Immunology
Shao-Qiu He, Qian Xu, Vinod Tiwari, Fei Yang, Michael Anderson, Zhiyong Chen, Shaness A Grenald, Srinivasa N Raja, Xinzhong Dong, Yun Guan
The μ-opioid receptor (MOR) agonist morphine is commonly used for pain management, but it has severe adverse effects and produces analgesic tolerance. Thus, alternative ways of stimulating MOR activity are needed. We found that MrgC11, a sensory neuron-specific G protein-coupled receptor, may form heteromeric complexes with MOR. Peptide-mediated activation of MrgC11 enhanced MOR recycling by inducing coendocytosis and sorting of MOR for membrane reinsertion. MrgC11 activation also inhibited the coupling of MOR to β-arrestin-2 and enhanced the morphine-dependent inhibition of cAMP production...
June 19, 2018: Science Signaling
John K Chan, William Brady, Bradley J Monk, Jubilee Brown, Mark S Shahin, Peter G Rose, Jae-Hoon Kim, Angeles Alvarez Secord, Joan L Walker, David M Gershenson
OBJECTIVES: To determine the efficacy and tolerability of sunitinib in recurrent or persistent clear cell ovarian cancer patients. METHODS: All patients had one or two prior regimens with measurable disease. Tumors were at least 50% clear cell histomorphology and negative for WT-1 antigen and estrogen receptor expression by immunohistochemistry. Sunitinib 50 mg per day for 4 weeks was administered in repeated 6-week cycles until disease progression or prohibitive toxicity...
June 16, 2018: Gynecologic Oncology
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