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Tolerance induction

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https://www.readbyqxmd.com/read/29786147/timing-and-frequency-of-sublethal-exposure-modifies-the-induction-and-retention-of-increased-insecticide-tolerance-in-wood-frogs-lithobates-sylvaticus
#1
Devin K Jones, Erika K Yates, Brian M Mattes, William D Hintz, Matthew S Schuler, Rick A Relyea
While the paradigm for increased tolerance to pesticides has been by selection on constitutive (naïve) traits, recent research has shown it can also occur through phenotypic plasticity. However, the time period in which induction can occur, the duration of induced tolerance, and the influence of multiple induction events remain unknown. We hypothesized that the induction of increased pesticide tolerance is limited to early sensitive periods, the magnitude of induced tolerance depends on the number of exposures, and the retention of induced tolerance depends on the time elapsed after an exposure and the number of exposures...
May 22, 2018: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/29785311/acute-lymphoblastic-leukemia-following-lenalidomide-maintenance-for-multiple-myeloma-two-cases-with-unexpected-presentation-and-good-prognostic-features
#2
Abdullah M Khan, Jameel Muzaffar, Hermant Murthy, John R Wingard, Jan S Moreb
Lenalidomide maintenance following autologous stem cell transplant (ASCT) is considered the standard of care for eligible patients with multiple myeloma (MM). A recent meta-analysis has provided additional evidence that lenalidomide maintenance is associated with a higher incidence of second primary malignancies, including both hematologic and solid malignancies. Acute lymphoblastic leukemia (ALL) as a second primary malignancy is rarely described in the literature. Herein, we describe two patients with MM treated with induction therapy, ASCT, and lenalidomide maintenance that experienced cytopenias while on maintenance...
2018: Case Reports in Hematology
https://www.readbyqxmd.com/read/29784793/camp-inducible-coactivator-crtc3-attenuates-brown-adipose-tissue-thermogenesis
#3
Young-Sil Yoon, Wen-Wei Tsai, Sam Van de Velde, Zhijiang Chen, Kuo-Fen Lee, Donald A Morgan, Kamal Rahmouni, Shigenobu Matsumura, Ezra Wiater, Youngsup Song, Marc Montminy
In response to cold exposure, placental mammals maintain body temperature by increasing sympathetic nerve activity in brown adipose tissue (BAT). Triggering of β-adrenergic receptors on brown adipocytes stimulates thermogenesis via induction of the cAMP/PKA pathway. Although cAMP response element-binding protein (CREB) and its coactivators-the cAMP-regulated transcriptional coactivators (CRTCs)-mediate transcriptional effects of cAMP in most tissues, other transcription factors such as ATF2 appear critical for induction of thermogenic genes by cAMP in BAT...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29784741/management-of-multiple-myeloma
#4
Shaji K Kumar
The most recent NCCN Guidelines for Multiple Myeloma include a ranking of the many treatment options for various settings as "preferred," "other," and "useful in certain circumstances." For patients eligible for autologous stem cell transplant (ASCT), the preferred regimen remains bortezomib/lenalidomide/dexamethasone (category 1) or bortezomib/cyclophosphamide/dexamethasone. Upfront ASCT also remains a preferred strategy for patients who are transplant-eligible, despite highly effective newer agents such as induction therapy...
May 2018: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/29781612/the-role-of-melatonin-in-affecting-cell-wall-disassembly-and-chilling-tolerance-in-cold-stored-peach-fruit
#5
Shifeng Cao, Kun Bian, Liyu Shi, Hsiao-Hang Chung, Wei Chen, Zhenfeng Yang
Melatonin reportedly increased chilling tolerance in postharvest peach fruit during cold storage but information on its effect on cell wall disassembly in chilling injured peaches is limited. In this study, we investigated the role of cell wall depolymerization in chilling tolerance induction in melatonin-treated peaches. Treatment with melatonin at 100 µM alleviated chilling symptom (mealiness) characterized by decrease in fruit firmness and increase in juice extractability in treated peaches during storage...
May 21, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29778403/the-cf-sputum-induction-trial-cf-spit-to-assess-lower-airway-bacterial-sampling-in-young-children-with-cystic-fibrosis-a-prospective-internally-controlled-interventional-trial
#6
Katherine Ronchetti, Jo-Dee Tame, Christopher Paisey, Lena P Thia, Iolo Doull, Robin Howe, Eshwar Mahenthiralingam, Julian T Forton
BACKGROUND: Pathogen surveillance is challenging but crucial in children with cystic fibrosis-who are often non-productive of sputum even if actively coughing-because infection and lung disease begin early in life. The role of sputum induction as a diagnostic tool for infection has not previously been systematically addressed in young children with cystic fibrosis. We aimed to assess the pathogen yield from sputum induction compared with that from cough swab and single-lobe, two-lobe, and six-lobe bronchoalveolar lavage...
May 16, 2018: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/29777502/oxi1-kinase-plays-a-key-role-in-resistance-of-arabidopsis-towards-aphids-myzus-persicae
#7
Tahsin Shoala, Martin G Edwards, Marc R Knight, Angharad M R Gatehouse
Plants have co-evolved with a diverse array of pathogens and insect herbivores and so have evolved an extensive repertoire of constitutive and induced defence mechanisms activated through complex signalling pathways. OXI1 kinase is required for activation of mitogen-activated protein kinases (MAPKs) and is an essential part of the signal transduction pathway linking oxidative burst signals to diverse downstream responses. Furthermore, changes in the levels of OXI1 appear to be crucial for appropriate signalling...
May 17, 2018: Transgenic Research
https://www.readbyqxmd.com/read/29773001/combined-administration-of-monosodium-glutamate-and-high-sucrose-diet-accelerates-the-induction-of-type-2-diabetes-vascular-dysfunction-and-memory-impairment-in-rats
#8
Kaja Saikrishna, Ringu Kumari, Kantamaneni Chaitanya, Subhankar Biswas, Pawan G Nayak, Jayesh Mudgal, Anoop Kishore, Krishnadas Nandakumar
In this study, we aimed to develop an experimental animal model for type 2 diabetes mellitus (T2DM) using a combination of monosodium glutamate (MSG) and high sucrose diet (HSD). Young male Wistar rats (20-30 g) were injected with MSG (2 or 4 mg/g, i.p. for 4 days). These rats were also fed an HSD, while the control group was fed a starch diet (SFD) for 150 days. Parameters assessed periodically were body weight, feed intake, blood glucose level, and oral glucose tolerance test (OGTT), lipid profile, liver and kidney function tests, skeletal muscle glucose uptake, cognitive function tests, and microvascular changes using isolated rat aorta...
2018: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/29772551/relevant-effects-of-beta-1-adrenoceptor-autoantibodies-in-chronic-heart-failure
#9
Valerie Boivin-Jahns, Roland Jahns, Fritz Boege
Patients suffering from chronic heart failure (CHF) caused or promoted by autoantibodies against cardiac beta1 -adrenergic receptors (beta1 AR) could benefit from specific therapies aimed at tolerance induction, removal or neutralisation of beta1 AR autoantibodies, provided the patients can be selected for these therapies by reliable detection and quantitation of beta1 AR autoantibodies in their circulation and by a valid assessment of the autoantibodies's putative cardio-pathogenic potential. Here, we discuss the current state of knowledge regarding the effects of CHF-associated (auto)antibodies on beta1 AR function and beta1 AR-mediated signal tranduction and discuss the presumed role of these effects in the development and progression of CHF...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29772544/antigen-specific-therapy-of-graves%C3%A2-disease-and-orbitopathy-by-induction-of-tolerance
#10
Martin Ungerer, Julia Fabbender, Hans-Peter Holthoff
Graves´ disease is an autoimmune disorder, which is characterized by stimulatory antibodies targeting the human thyrotropin receptor (TSHR), resulting in hyperthyroidism and multiple organ damage. The disease can be modelled in mice using adenoviral immunizations with the extracellular A subunit of the TSHR, which induces a long-term stable disease state. TSHR binding cAMP-stimulatory antibodies, thyroid enlargement, elevated serum thyroxin levels, tachycardia, cardiac hypertrophy and orbitopathy are observed in these Ad-TSHR-immunized mice...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29770489/melatonin-induction-and-its-role-in-high-light-stress-tolerance-in-arabidopsis-thaliana
#11
Hyoung Yool Lee, Kyoungwhan Back
In plants, melatonin is a potent bioactive molecule involved in the response against various biotic and abiotic stresses. However, little is known of its defensive role against high light (HL) stress. In this study, we found that melatonin was transiently induced in response to HL stress in Arabidopsis thaliana with a simultaneous increase in the expression of melatonin biosynthetic genes, including serotonin N-acetyltransferase1 (SNAT1). Transient induction of melatonin was also observed in the flu mutant, a singlet oxygen (1 O2 )-producing mutant, upon light exposure, suggestive of melatonin induction by chloroplastidic 1 O2 against HL stress...
May 16, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29769258/anti-tumor-efficacy-of-a-novel-clk-inhibitor-via-targeting-rna-splicing-and-myc-dependent-vulnerability
#12
Kenichi Iwai, Masahiro Yaguchi, Kazuho Nishimura, Yukiko Yamamoto, Toshiya Tamura, Daisuke Nakata, Ryo Dairiki, Yoichi Kawakita, Ryo Mizojiri, Yoshiteru Ito, Moriteru Asano, Hironobu Maezaki, Yusuke Nakayama, Misato Kaishima, Kozo Hayashi, Mika Teratani, Shuichi Miyakawa, Misa Iwatani, Maki Miyamoto, Michael G Klein, Wes Lane, Gyorgy Snell, Richard Tjhen, Xingyue He, Sai Pulukuri, Toshiyuki Nomura
The modulation of pre-mRNA splicing is proposed as an attractive anti-neoplastic strategy, especially for the cancers that exhibit aberrant pre-mRNA splicing. Here, we discovered that T-025 functions as an orally available and potent inhibitor of Cdc2-like kinases (CLKs), evolutionally conserved kinases that facilitate exon recognition in the splicing machinery. Treatment with T-025 reduced CLK-dependent phosphorylation, resulting in the induction of skipped exons, cell death, and growth suppression in vitro and in vivo Further, through growth inhibitory characterization, we identified high CLK2 expression or MYC amplification as a sensitive-associated biomarker of T-025...
May 16, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29767728/andecaliximab-anti-matrix-metalloproteinase-9-induction-therapy-for-ulcerative-colitis-a-randomised-double-blind-placebo-controlled-phase-2-3-study-in-patients-with-moderate-to-severe-disease
#13
William J Sandborn, Bal R Bhandari, Charles Randall, Ziad H Younes, Tomasz Romanczyk, Yan Xin, Emily Wendt, Hao Chai, Matt McKevitt, Sally Zhao, John S Sundy, Satish Keshav, Silvio Danese
Background and Aims: Matrix metalloproteinase-9 [MMP9] is implicated in the pathogenesis of ulcerative colitis [UC] via disruption of intestinal barrier integrity and function. A phase 2/3 combined trial was designed to examine the efficacy, safety, and pharmacokinetics of the anti-MMP9 antibody, andecaliximab [formerly GS-5745], in patients with moderately to severely active UC. Methods: Patients were randomised [1:1:1] to receive placebo, 150 mg andecaliximab every 2 weeks [Q2W], or 150 mg andecaliximab weekly [QW], via subcutaneous administration...
May 14, 2018: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29765321/brain-lipopolysaccharide-preconditioning-induced-gene-reprogramming-mediates-a-tolerance-state-in-electroconvulsive-shock-model-of-epilepsy
#14
Elham Amini, Mojtaba Golpich, Abdoreza S Farjam, Behnam Kamalidehghan, Zahurin Mohamed, Norlinah M Ibrahim, Abolhassan Ahmadiani, Azman A Raymond
There is increasing evidence pointing toward the role of inflammatory processes in epileptic seizures, and reciprocally, prolonged seizures induce more inflammation in the brain. In this regard, effective strategies to control epilepsy resulting from neuroinflammation could be targeted. Based on the available data, preconditioning (PC) with low dose lipopolysaccharide (LPS) through the regulation of the TLR4 signaling pathway provides neuroprotection against subsequent challenge with injury in the brain. To test this, we examined the effects of a single and chronic brain LPS PC, which is expected to lead to reduction of inflammation against epileptic seizures induced by electroconvulsive shock (ECS)...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29762875/in-vivo-assessment-of-the-effect-of-cyp1a2-inhibition-and-induction-on-pomalidomide-pharmacokinetics-in-healthy-subjects
#15
Yan Li, Liangang Liu, Xiaomin Wang, Chengyue Zhang, Josephine Reyes, Matthew Hoffmann, Maria Palmisano, Simon Zhou
Pomalidomide is an immunomodulatory drug, and the dosage of 4 mg per day taken orally on days 1-21 of repeated 28-day cycles has been approved in the European Union and the United States to treat patients with relapsed/refractory multiple myeloma. In vitro data showed that pomalidomide is a substrate of multiple cytochrome P450 (CYP) isozymes and that its oxidative metabolism is mediated primarily by CYP1A2 and CYP3A4, with minor contributions from CYP2C19 and CYP2D6. The effect of CYP1A2 inhibition by fluvoxamine (a strong CYP1A2 inhibitor) and CYP1A2 induction by smoking on pomalidomide pharmacokinetics in healthy subjects has been assessed in 2 separate phase 1 open-label, single-dose studies...
May 15, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29762106/metal-induction-of-two-metallothionein-genes-in-the-ectomycorrhizal-fungus-suillus-himalayensis-and-their-role-in-metal-tolerance
#16
Tania Kalsotra, Shikha Khullar, Radhika Agnihotri, Mondem Sudhakara Reddy
Metallothioneins (MTs) are small proteins with highly conserved cysteine residues and are involved in metal homeostasis and metal detoxification. Two metallothionein genes ShMT1 and ShMT2 from the ectomycorrhizal fungus Suillus himalayensis were characterised for their potential role in heavy metal detoxification. The response of these MTs to the exogenous concentrations of copper and cadmium was studied by qPCR analysis. The exogenous copper but not the cadmium at the tested concentrations induced the expression of the MT genes...
May 15, 2018: Microbiology
https://www.readbyqxmd.com/read/29760711/selective-modulation-of-tnf-tnfrs-signaling-insights-for-multiple-sclerosis-treatment
#17
REVIEW
Valentina Pegoretti, Wia Baron, Jon D Laman, Ulrich L M Eisel
Autoimmunity develops when self-tolerance mechanisms are failing to protect healthy tissue. A sustained reaction to self is generated, which includes the generation of effector cells and molecules that destroy tissues. A way to restore this intrinsic tolerance is through immune modulation that aims at refurbishing this immunologically naïve or unresponsive state, thereby decreasing the aberrant immune reaction taking place. One major cytokine has been shown to play a pivotal role in several autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS): tumor necrosis factor alpha (TNFα) modulates the induction and maintenance of an inflammatory process and it comes in two variants, soluble TNF (solTNF) and transmembrane bound TNF (tmTNF)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29760702/emerging-concepts-in-immune-thrombocytopenia
#18
REVIEW
Maurice Swinkels, Maaike Rijkers, Jan Voorberg, Gestur Vidarsson, Frank W G Leebeek, A J Gerard Jansen
Immune thrombocytopenia (ITP) is an autoimmune disease defined by low platelet counts which presents with an increased bleeding risk. Several genetic risk factors (e.g., polymorphisms in immunity-related genes) predispose to ITP. Autoantibodies and cytotoxic CD8+ T cells (Tc) mediate the anti-platelet response leading to thrombocytopenia. Both effector arms enhance platelet clearance through phagocytosis by splenic macrophages or dendritic cells and by induction of apoptosis. Meanwhile, platelet production is inhibited by CD8+ Tc targeting megakaryocytes in the bone marrow...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29758056/assessment-of-the-behaviour-and-survival-of-nematodes-under-low-oxygen-concentrations
#19
Hiromi Kitazume, Mehmet Dayi, Ryusei Tanaka, Taisei Kikuchi
Oxygen is required for the completion of almost all known metazoan lifecycles, but many metazoans harbour abilities to withstand varying degrees and periods of hypoxia. Caenorhabditis elegans, one of the most popular model organism is extensively used as a model for the study of hypoxia and anoxia biology and it has been found that this nematode is capable of tolerance to varying degrees of hypoxia. Considering the extremely high diversity of nematodes, the effects of low oxygen concentration and mechanisms of adaptation to oxygen depletion differ among species...
2018: PloS One
https://www.readbyqxmd.com/read/29753302/contribution-of-hepatic-retinaldehyde-dehydrogenase-induction-to-impairment-of-glucose-metabolism-by-high-fat-diet-feeding-in-c57bl-6j-mice
#20
Jiong Xu, Mian Zhang, Xiangping Zhang, Hanyu Yang, Binbin Sun, Zhongjian Wang, Yaqian Zhou, Shuting Wang, Xiaodong Liu, Li Liu
Obesity and insulin resistance are associated with overexpression of retinaldehyde dehydrogenase 1 (RALDH1). We aimed to investigate the roles of hepatic RALDH1 induction in glucose metabolism impairment using mice fed with high-fat diet (HFD). Mice were fed with HFD for 8 weeks and treated with RALDH inhibitor citral for another 4 weeks. Oral glucose tolerance test (OGTT), pyruvate tolerance test (PTT) and insulin tolerance test (ITT) were operated. Expressions of Phosphoenolpyruvate carboxykinase 1 (PCK1), glucokinase (GCK) and RALDH1 were measured...
May 12, 2018: Basic & Clinical Pharmacology & Toxicology
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