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tolerance mechanism

Lisa-Marie Niestroj, Juanjiangmeng Du, Michael Nothnagel, Patrick May, Aarno Palotie, Mark J Daly, Peter Nürnberg, Ingmar Blümcke, Dennis Lal
OBJECTIVE: Increasing availability of surgically resected brain tissue from patients with focal epilepsy and focal cortical dysplasia or low-grade glioneuronal tumors has fostered large-scale genetic examination. However, assessment of pathogenicity of germ line and somatic variants remains difficult. Here, we present a state-of-the-art evaluation of reported genes and variants associated with epileptic brain lesions. METHODS: We critically reevaluated the pathogenicity for all neuropathology-associated variants reported to date in the PubMed and ClinVar databases, including 101 neuropathology-associated missense variants encompassing 11 disease-related genes...
October 20, 2018: Epilepsia
Anna Kordowski, Anna T Reinicke, David Wu, Zane Orinska, Philipp Hagemann, Markus Huber-Lang, Jee-Boong Lee, Yui-Hsi Wang, Simon P Hogan, Jörg Köhl
BACKGROUND: Food-induced anaphylaxis is a serious allergic reaction caused by Fcε-receptor activation on mast cells (MCs). The exact mechanisms breaking oral tolerance and the effector pathways driving food allergy remain elusive. As complement is activated in food-induced anaphylaxis, we aimed to assess the role of C5a in disease pathogenesis. METHODS: Oral antigen-induced food-induced anaphylaxis was induced in BALB/c wildtype (wt) and C5ar1-/- mice. Readouts included diarrhea development, changes in rectal temperature, hematocrit, antigen-specific serum IgE, MCPT-1 and intestinal MC numbers as well as FcεR1-mediated MC functions including C5a receptor 1 (C5aR1) regulation...
October 19, 2018: Allergy
Takaaki Horinouchi, Tomoya Maeda, Chikara Furusawa
Microbes are capable of producing alcohols, making them an important source of alternative energy that can replace fossil fuels. However, these alcohols can be toxic to the microbes themselves, retaring or inhibiting cell growth and decreasing the production yield. One solution is improving the alcohol tolerance of such alcohol-producing organisms. Advances in omics technologies, including transcriptomic, proteomic, metabolomic, and genomic technologies, have helped us understand the complex mechanisms underlying alcohol toxicity, and such advances could assist in devising strategies for engineering alcohol-tolerant strains...
October 19, 2018: World Journal of Microbiology & Biotechnology
Travis Rush, Jose Martinez-Hernandez, Marc Dollmeyer, Marie Lise Frandemiche, Eve Borel, Sylvie Boisseau, Muriel Jacquier-Sarlin, Alain Buisson
Amyloid-β (Aβ) drives the synaptic impairment and dendritic spine loss characteristic of Alzheimer's disease (AD), but how Aβ affects the actin cytoskeleton remains unknown and contentious. The actin-binding protein, cofilin-1 (cof1), is a major regulator of actin dynamics in dendritic spines, and is subject to phospho-regulation by multiple pathways, including the Rho-associated protein kinase (ROCK) pathway. While cof1 is implicated as a driver of the synaptotoxicity characteristic of the early phases of AD pathophysiology, questions remain about the molecular mechanisms involved...
October 19, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Jenny Peng, Chantalle Clarkin, Asif Doja
OBJECTIVE: The development of cynicism in medicine, defined as a decline in empathy and emotional neutralisation during medical training, is a significant concern for medical educators. We sought to use online medical student discussion groups to provide insight into how cynicism in medicine is perceived, the consequences of cynicism on medical trainee development and potential links between the hidden curriculum and cynicism. SETTING: Online analysis of discussion topics in Premed101 (Canadian) and Student Doctor Network (American) forums...
October 18, 2018: BMJ Open
Sikander Ailawadhi, Kevin R Kelly, Robert A Vescio, Sundar Jagannath, Jeffrey Wolf, Mecide Gharibo, Taimur Sher, Leyla Bojanini, Maurice Kirby, Asher Chanan-Khan
BACKGROUND: Despite therapeutic advancements that have significantly improved outcomes in multiple myeloma (MM), it remains an incurable disease. Patients with relapsed and/or refractory MM have an aggressive disease course, with inferior outcomes, necessitating the need for agents with novel therapeutic mechanisms. We present the results of a completed phase I trial of single-agent lorvotuzumab mertansine, a unique antibody-drug conjugate targeting CD56, which is frequently expressed in MM...
September 5, 2018: Clinical Lymphoma, Myeloma & Leukemia
George R Schade, Yak-Nam Wang, Samantha D'Andrea, Joo Ha Hwang, W Conrad Liles, Tatiana D Khokhlova
Boiling histotripsy (BH) is an experimental focused ultrasound technique that produces non-thermal mechanical ablation. We evaluated the feasibility, short-term histologic effects and the resulting acute inflammatory response to BH ablation of renal cell carcinoma (RCC) in the Eker rat. Genotyped Eker rats were monitored for de novo RCCs with serial ultrasound (US) imaging. When tumors were ≥8mm, rats underwent ultrasound-guided extracorporeal ablation of the tumor with BH, a pulsed focused US technique that produces non-thermal mechanical ablation of targeted tissues, or a sham US procedure...
October 16, 2018: Ultrasound in Medicine & Biology
Hong-Di Ma, Zhi-Bin Zhao, Wen-Tao Ma, Qing-Zhi Liu, Cai-Yue Gao, Liang Li, Jinjun Wang, Koichi Tsuneyama, Bin Liu, Weici Zhang, Yongjian Zhou, M Eric Gershwin, Zhe-Xiong Lian
Gut microbiota and bacterial translocation have been implicated as significant contributors to mucosal immune responses and tolerance; alteration of microbial molecules, termed pathogen-associated molecular patterns (PAMP) and bacterial translocation are associated with immune pathology. However, the mechanisms by which dysregulated gut microbiota promotes autoimmunity is unclear. We have taken advantage of a well-characterized murine model of primary biliary cholangitis, dnTGFβRII mice, and an additional unique construct, toll-like receptor 2 (TLR2)-deficient dnTGFβRII mice coined dnTGFβRIITLR2-/- mice to investigate the influences of gut microbiota on autoimmune cholangitis...
October 16, 2018: Journal of Autoimmunity
Baohua Feng, Caixia Zhang, Tingting Chen, Xiufu Zhang, Longxing Tao, Guanfu Fu
BACKGROUND: Extremely high temperatures are becoming an increasingly severe threat to crop yields. It is well documented that salicylic acid (SA) can enhance the stress tolerance of plants; however, its effect on the reproductive organs of rice plants has not been described before. To investigate the mechanism underlying the SA-mediated alleviation of the heat stress damage to rice pollen viability, a susceptible cultivar (Changyou1) was treated with SA at the pollen mother cell (PMC) meiosis stage and then subjected to heat stress of 40 °C for 10 d until 1d before flowering...
October 19, 2018: BMC Plant Biology
Lei Dou, Yahong Zheng, Lu Li, Xiaowei Gui, Yajuan Chen, Meng Yu, Yi Guo
BACKGROUND: Polycystic ovary syndrome (PCOS) is the most prevalent cause of anovulatory infertility and hyperandrogenism. Evidence favors insulin resistance and compensatory hyperinsulinemia as the predominant, perhaps primary, defects in PCOS. The use of insulin-sensitizing drugs has been shown to improve both the reproductive and the metabolic aspects of PCOS. Cinnamon has been found to have insulin sensitizing effect and improve menstrual cyclicity in women with PCOS. The aim of this study was to determine the effect and mechanism of cinnamon on PCOS using a dehydroepiandrosterone (DHEA) induced PCOS mouse model...
October 19, 2018: Reproductive Biology and Endocrinology: RB&E
Tinashe Zenda, Songtao Liu, Xuan Wang, Hongyu Jin, Guo Liu, Huijun Duan
Drought stress is the major abiotic factor threatening maize ( Zea mays L.) yield globally. Therefore, revealing the molecular mechanisms fundamental to drought tolerance in maize becomes imperative. Herein, we conducted a comprehensive comparative analysis of two maize inbred lines contrasting in drought stress tolerance based on their physiological and proteomic responses at the seedling stage. Our observations showed that divergent stress tolerance mechanisms exist between the two inbred-lines at physiological and proteomic levels, with YE8112 being comparatively more tolerant than MO17 owing to its maintenance of higher relative leaf water and proline contents, greater increase in peroxidase (POD) activity, along with decreased level of lipid peroxidation under stressed conditions...
October 18, 2018: International Journal of Molecular Sciences
Kaize Ma, Ting Qi, Huijie Liu, Hongbing Wang
Hybrid fiber reinforced concrete (HFRC) is based on a multilevel-reinforcement material design that improves both the compressive strength and tensile strength. Investigations of the mechanical performance of HFRC with two types of steel fibers were conducted experimentally. The investigated parameters were the volume fractions of the short steel fibers and long steel fibers. The compressive strength, tensile strength, and flexural strength of the HFRC were researched. The group with volume fractions of 1.5% for the long steel fibers and 0...
October 18, 2018: Materials
Gabhan Chalmers, Kelly M Rozas, Raghavendra G Amachawadi, Harvey Morgan Scott, Keri N Norman, Tiruvoor G Nagaraja, Mike D Tokach, Patrick Boerlin
Copper is used as an alternative to antibiotics for growth promotion and disease prevention. However, bacteria developed tolerance mechanisms for elevated copper concentrations, including those encoded by the pco operon in Gram-negative bacteria. Using cohorts of weaned piglets, this study showed that the supplementation of feed with copper concentrations as used in the field did not result in a significant short-term increase in the proportion of pco -positive fecal Escherichia coli . The pco and sil (silver resistance) operons were found concurrently in all screened isolates, and whole-genome sequencing showed that they were distributed among a diversity of unrelated E...
October 18, 2018: Genes
Junzhi Yang, Bianca G Reilly, Thomas P Davis, Patrick T Ronaldson
Opioids are highly effective analgesics that have a serious potential for adverse drug reactions and for development of addiction and tolerance. Since the use of opioids has escalated in recent years, it is increasingly important to understand biological mechanisms that can increase the probability of opioid-associated adverse events occurring in patient populations. This is emphasized by the current opioid epidemic in the United States where opioid analgesics are frequently abused and misused. It has been established that the effectiveness of opioids is maximized when these drugs readily access opioid receptors in the central nervous system (CNS)...
October 18, 2018: Pharmaceutics
Cheng Liu, Fei Li, Jing Wu, Xin Hou, Wei Huang, Yong Zhang, Xiangguang Yang
The MOx (M = Cu, Mn, Co)/CePO4 support was firstly prepared via the hydrothermal and impregnated method. Selective catalytic reduction of NO with NH3 (NH3 -SCR) results showed that the MnOx modifications greatly improved the SCR activities at low temperatures. The NOx conversion of the MnOx /CePO4 catalyst was above 80% even at 180 °C. In-situ DRIFTS results suggest that the SCR reaction is majorly conducted between the absorbed monodentate nitrate and NH3 species (i.e., the Langmuir-Hinshelwood mechanism)...
September 24, 2018: Journal of Hazardous Materials
Jun Zhou, Buyun Du, Yuanmei Hu, Jiani Liang, Hailong Liu, Xingjun Fan, Ligan Zhang, Hongbiao Cui, Xiaoli Liu, Jing Zhou
There is an increasing evidence linking protective effect of selenium (Se) against Pb toxicology; however, Pb exposure risk assessments usually consider only the environmental Pb contamination and dietary intake. Based on the current understanding of mechanisms of SePb interactions, the physiological function/toxicology of Se and the toxicology of Pb, a new criterion for Se and Pb exposure assessment is developed. Additionally, seven existing criteria were also used to assess the resident health risks around a smelter in China...
October 8, 2018: Environmental Pollution
Jie Gu, Sha Song, Huiying Han, Hongxia Xu, Gao Fan, Chen'ao Qian, Yingchun Qiu, Wenqi Zhou, Wenzhuo Zhuang, Bingzong Li
Treatment failure remains a main challenge in the management of high-risk multiple myeloma (MM) even with the expanding repertoire of new drugs. Combinatorial therapy is considered an encouraging strategy that can overcome the compensatory mechanisms and undesirable off-target effects that limit the benefits of many prospective agents. Preliminary results of a current phase I trial have indicated that the new BET bromodomain inhibitor OTX015 has favorable activity and tolerability. However, OTX015 is not efficacious enough as a monotherapy...
October 19, 2018: Molecular Pharmaceutics
Michael Di Gioacchino, Fabio Bruni, Maria Antonietta Ricci
The ability of a wide class of organisms to reversibly go through cycles of suspended life and active metabolism, depending on the turnover of drought and normal water availability conditions, represents a challenging issue. The interest in the natural mechanism for drought survival has grown over time along with the request for always more efficient conservation techniques for biological materials. Carbohydrates, such as trehalose, accumulated in the cytoplasm of drought resistant cells, are considered responsible for desiccation tolerance...
October 19, 2018: Journal of Physical Chemistry. B
Xin Yang, Caiji Zhang, Guozhen Chen, Chengming Sun, Jinming Li
The aim of this study is to improve our understanding of the mechanisms involved in maternal-fetal immune tolerance. We searched the related literatures and overviewed the major antibodies associated with pregnancy and described in details their possible roles in mediating maternal-fetal interactions. Antibodies classified into different types based on their functional or structural characteristics were summarized, including immunoglobulin G, blocking antibody, nonprecipitating asymmetric antibody, antiphospholipid antibody, antitrophoblast antibody and antipaternal antibody...
October 19, 2018: Journal of Obstetrics and Gynaecology Research
Roberta Semprini, Alessandro Martorana, Mauro Ragonese, Caterina Motta
BACKGROUND: Painful distal symmetric polyneuropathy (pDSPN) is one of the most common and invalidating complications of diabetes mellitus, both of type 1 and type 2. Mechanisms responsible for the occurrence of the pDSPN are multifactorial and involve metabolic pathways regulating inflammation, microvessel circulation, axonal degeneration and so on. Several therapeutic approaches have been proposed to treat pain and each of them showed positive effects associated to drug-related side effects...
October 2018: Minerva Medica
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