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https://www.readbyqxmd.com/read/28346823/design-and-monitoring-of-multi-arm-multi-stage-clinical-trials
#1
Pranab Ghosh, Lingyun Liu, P Senchaudhuri, Ping Gao, Cyrus Mehta
Two-arm group sequential designs have been widely used for over 40 years, especially for studies with mortality endpoints. The natural generalization of such designs to trials with multiple treatment arms and a common control (MAMS designs) has, however, been implemented rarely. While the statistical methodology for this extension is clear, the main limitation has been an efficient way to perform the computations. Past efforts were hampered by algorithms that were computationally explosive. With the increasing interest in adaptive designs, platform designs, and other innovative designs that involve multiple comparisons over multiple stages, the importance of MAMS designs is growing rapidly...
March 27, 2017: Biometrics
https://www.readbyqxmd.com/read/28345658/nephronectin-plays-critical-roles-in-sox2-expression-and-proliferation-in-dental-epithelial-stem-cells-via-egf-like-repeat-domains
#2
Chieko Arai, Keigo Yoshizaki, Kanako Miyazaki, Kan Saito, Aya Yamada, Xue Han, Keita Funada, Emiko Fukumoto, Naoto Haruyama, Tsutomu Iwamoto, Ichiro Takahashi, Satoshi Fukumoto
Tooth development is initiated by epithelial-mesenchymal interactions via basement membrane (BM) and growth factors. In the present study, we found that nephronectin (Npnt), a component of the BM, is highly expressed in the developing tooth. Npnt localizes in the BM on the buccal side of the tooth germ and shows an expression pattern opposite that of the dental epithelial stem cell marker Sox2. To identify the roles of Npnt during tooth development, we performed knockdown and overexpression experiments using ex vivo organ and dental epithelial cell cultures...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28335030/urinary-kinetics-of-heroin-metabolites-in-pigs-shortly-after-intake
#3
Gudrun Høiseth, André Gottås, Thomas Berg, Marianne Arnestad, Per Steinar Halvorsen, Liliana C Bachs
In previous experimental studies on heroin metabolites excretion in urine, the first sample was often collected a few hours after intake. In forensic cases, it is sometimes questioned if a positive urine result is expected e.g., 30 min after intake. The aim of this study was to investigate urinary excretion of heroin metabolites (morphine, 6-monoacetylmorphine (6-MAM) and morphine-3-glucuronide (M3G)) every 30 min until 330 min after injection of a 20 mg heroin dose in six pigs. Samples were analyzed using a previously published, fully validated liquid chromatography-tandem mass spectrometry method...
February 27, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/28333105/anti-melanogenic-properties-of-greek-plants-a-novel-depigmenting-agent-from-morus-alba-wood
#4
Eliza Chaita, George Lambrinidis, Christina Cheimonidi, Adamantia Agalou, Dimitris Beis, Ioannis Trougakos, Emmanuel Mikros, Alexios-Leandros Skaltsounis, Nektarios Aligiannis
In therapeutic interventions associated with melanin hyperpigmentation, tyrosinase is regarded as a target enzyme as it catalyzes the rate-limiting steps in mammalian melanogenesis. Since many known agents have been proven to be toxic, there has been increasing impetus to identify alternative tyrosinase inhibitors, especially from natural sources. In this study, we investigated 900 extracts from Greek plants for potential tyrosinase inhibitive properties. Among the five most potent extracts, the methanol extract of Morus alba wood (MAM) demonstrated a significant reduction in intracellular tyrosinase and melanin content in B16F10 melanoma cells...
March 23, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28324201/potential-roles-of-mitochondria-associated-er-membranes-mams-in-traumatic-brain-injury
#5
REVIEW
Dongdong Sun, Xin Chen, Gang Gu, Jianhao Wang, Jianning Zhang
The endoplasmic reticulum (ER) and mitochondria have both been shown to be critical in cellular homeostasis. The functions of the ER and mitochondria are independent but interrelated. These two organelles could form physical interactions, known as MAMs, to regulate physiological functions between ER and mitochondria to maintain Ca(2+), lipid, and metabolite exchange. Several proteins are located in MAMs, including RNA-dependent protein kinase (PKR)-like ER kinase, inositol 1,4,5-trisphosphate receptors, phosphofurin acidic cluster sorting protein-2 and sigma-1 receptor to ensure regulation...
March 21, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28318317/characterization-kinetics-and-thermodynamics-of-biosynthesized-uranium-nanoparticles-unps
#6
Mervate Aly Abostate, Youssry Saleh, Hamed Mira, Maysa Amin, Maha Al Kazindar, Basma Mahmoud Ahmed
The present study was carried out to explore the potential of the isolated bacterial strains isolated from Gabal El Sela in Eastern Dessert, Egypt for biosynthesis of uraninite nanoparticles intracellularly. The most potent bacterial strains associated (intra) with uranium nanoparticles were characterized by transmission electron microscope (TEM), Fourier transform infrared (FTIR) and Energy Dispersive X-ray (EDX). Studying factors affecting biosynthesis of uranium nanoparticles indicated that the optimum conditions were 6000 ppm uranium concentrations at pH 7...
March 20, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28318177/can-soluble-transferrin-receptor-be-used-in-diagnosing-iron-deficiency-anemia-and-assessing-iron-response-in-infants-with-moderate-acute-malnutrition
#7
Bahar Bu Yu Kkaragöz, Necat A Akgun, Ayse D Bulus, Sultan Durmus Aydogdu, Cengiz Bal
OBJECTIVE: To evaluate the efficacy of soluble transferrin receptor (sTfR) in diagnosing iron deficiency anemia (IDA) and evaluating iron response in infants with moderate acute malnutrition (MAM). POPULATION AND METHODS: Infants with hemoglobin (Hb) levels lower than threshold values for anemia for their ages and hypochromic/ microcytic anemia on peripheral smear were recruited. MAM was defined as weight/height z score < -2 to -3. Complete blood count (CBC), iron parameters and sTfR were compared among 41 infants with MAM and anemia (MA group), 32 infants with anemia without MAM (group A), and healthy controls (n= 30)...
April 1, 2017: Archivos Argentinos de Pediatría
https://www.readbyqxmd.com/read/28315271/role-of-sigma-1-receptor-in-cocaine-abuse-and-neurodegenerative-disease
#8
Yu Cai, Lu Yang, Fang Niu, Ke Liao, Shilpa Buch
Sigma-1 receptors (Sig-1R) are recognized as a unique class of non-G protein-coupled intracellular protein. Sig-1R binds to its ligand such as cocaine , resulting in dissociation of Sig-1R from mitochondrion-associated ER membrane (MAM) to the endoplasmic reticulum (ER), plasma membrane, and nuclear membrane, regulating function of various proteins. Sig-1R has diverse roles in both physiological as well as in pathogenic processes. The disruption of Sig-1R pathways has been implicated as causative mechanism(s) in the development of both neurodegenerative disorders such as Alzheimer disease (AD ), Parkinson disease (PD ), amyotrophic lateral sclerosis (ALS ) and Huntington Disease (HD ) ...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28315266/sigma-1-receptors-fine-tune-the-neuronal-networks
#9
Shang-Yi Anne Tsai, Tsung-Ping Su
The endoplasmic reticular (ER) protein sigma-1 receptor (Sig-1R) has been implicated in CNS disorders including but not limited to neurodegenerative diseases, depression , amnesia, and substance abuse. Sig-1Rs are particularly enriched in the specific domain where ER membranes make contacts with the mitochondria (MAM). Within that specific domain, Sig-1Rs play significant roles governing calcium signaling and reactive oxygen species homeostasis to maintain proper neuronal functions. Studies showed that the Sig-1R is pivotal to regulate neuroplasticity and neural survival via multiple aspects of mechanism...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28288859/mitochondrial-toxicity-of-perfluorooctane-sulfonate-in-mouse-embryonic-stem-cell-derived-cardiomyocytes
#10
Lei-Lei Tang, Jia-Dan Wang, Ting-Ting Xu, Zhe Zhao, Jia-Jie Zheng, Ren-Shan Ge, Dan-Yan Zhu
Perfluorooctane sulfonate (PFOS) is a persistent organic contaminant that may cause cardiotoxicity in animals and humans. However, little is known about the underlying mechanism by which it affects the organelle toxicity in cardiomyocytes during the cardiogenesis. Our previous proteomic study showed that differences of protein expression mainly existed in mitochondria of cardiomyocytes differentiated from embryonic stem (ES) cells after exposure to PFOS. Here, we focused on mitochondrial toxicity of PFOS in ES cell-derived cardiomyocytes...
March 10, 2017: Toxicology
https://www.readbyqxmd.com/read/28287490/correlations-between-maternal-breast-milk-and-infant-vitamin-b12-concentrations-among-mother-infant-dyads-in-vancouver-canada-and-prey-veng-cambodia-an-exploratory-analysis
#11
Philip Chebaya, Crystal D Karakochuk, Kaitlin M March, Nancy N Chen, Rosemary A Stamm, Hou Kroeun, Prak Sophonneary, Mam Borath, Setareh Shahab-Ferdows, Daniela Hampel, Susan I Barr, Yvonne Lamers, Lisa A Houghton, Lindsay H Allen, Tim J Green, Kyly C Whitfield
Vitamin B12 plays an essential role in fetal and infant development. In regions where animal source food consumption is low and perinatal supplementation is uncommon, infants are at risk of vitamin B12 deficiency. In this secondary analysis, we measured total vitamin B12 concentrations in maternal and infant serum/plasma and breast milk among two samples of mother-infant dyads in Canada (assessed at 8 weeks post-partum) and in Cambodia (assessed between 3-27 weeks post-partum). Canadian mothers (n = 124) consumed a daily vitamin B12-containing multiple micronutrient supplement throughout pregnancy and lactation; Cambodian mothers (n = 69) were unsupplemented...
March 12, 2017: Nutrients
https://www.readbyqxmd.com/read/28276013/isolation-of-mitochondria-associated-membranes-mam-from-mouse-brain-tissue
#12
Bernadette Schreiner, Maria Ankarcrona
During the last decades, increasing evidence indicated that subcellular organelles do not exist as autarkic units but instead communicate constantly and extensively with each other in various ways. Some communication, for example, the exchange of small molecules, requires the marked convergence of two distinct organelles for a certain period of time. The cross talk between endoplasmic reticulum (ER) and mitochondria, two subcellular organelles of utmost importance for cellular bioenergetics and protein homeostasis, has been increasingly investigated under the last years...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28275724/mitochondrial-metabolic-regulation-by-grp78
#13
Manoj Prasad, Kevin J Pawlak, William E Burak, Elizabeth E Perry, Brendan Marshall, Randy M Whittal, Himangshu S Bose
Steroids, essential for mammalian survival, are initiated by cholesterol transport by steroidogenic acute regulatory protein (StAR). Appropriate protein folding is an essential requirement of activity. Endoplasmic reticulum (ER) chaperones assist in folding of cytoplasmic proteins, whereas mitochondrial chaperones fold only mitochondrial proteins. We show that glucose regulatory protein 78 (GRP78), a master ER chaperone, is also present at the mitochondria-associated ER membrane (MAM), where it folds StAR for delivery to the outer mitochondrial membrane...
February 2017: Science Advances
https://www.readbyqxmd.com/read/28263689/comparison-of-breast-cancer-risk-predictive-models-and-screening-strategies-for-chinese-women
#14
Ying Zhao, Ping Xiong, Lauren E McCullough, Erline E Miller, Hui Li, Yuan Huang, Min Zhao, Meng-Jie Wang, Min Kang, Qiong Wang, Jia-Yuan Li
BACKGROUND: Previous studies have shown that organized mammographic screening implementation in China may not be cost-effective. Our aim was to develop a valid predictive mathematical model for selecting high-risk groups eligible for mammography examinations (MAMs) and cost-effective strategies for breast cancer screening among Chinese women. METHODS: Between 2009 and 2012, 13,355 eligible women aged 30-65 years were enrolled from the community in Chengdu City. All subjects were administered a valid questionnaire and given MAMs...
March 2017: Journal of Women's Health
https://www.readbyqxmd.com/read/28246299/on-the-pathogenesis-of-alzheimer-s-disease-the-mam-hypothesis
#15
REVIEW
Estela Area-Gomez, Eric A Schon
The pathogenesis of Alzheimer's disease (AD) is currently unclear and is the subject of much debate. The most widely accepted hypothesis designed to explain AD pathogenesis is the amyloid cascade, which invokes the accumulation of extracellular plaques and intracellular tangles as playing a fundamental role in the course and progression of the disease. However, besides plaques and tangles, other biochemical and morphological features are also present in AD, often manifesting early in the course of the disease before the accumulation of plaques and tangles...
March 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28243593/low-impact-of-avian-pox-on-captive-bred-houbara-bustard-breeding-performance
#16
Guillaume Le Loc'h, Mam-Noury Amadou Souley, Stéphane Bertagnoli, Mathilde C Paul
Avian pox, a disease caused by avipoxviruses, is a major cause of decline of some endangered bird species. While its impact has been assessed in several species in the wild, effects of the disease in conservation breeding have never been studied. Houbara bustard species (Chlamydotis undulata and Chlamydotis macqueenii), whose populations declined in the last decades, have been captive bred for conservation purposes for more than 20 years. While mortality and morbidity induced by avipoxviruses can be controlled by appropriate management, the disease might still affect bird breeding performance and jeopardize the production objectives of conservation programs...
2017: Frontiers in Veterinary Science
https://www.readbyqxmd.com/read/28213064/juvenile-treatment-with-a-novel-mglur2-agonist-mglur3-antagonist-compound-ly395756-reverses-learning-deficits-and-cognitive-flexibility-impairments-in-adults-in-a-neurodevelopmental-model-of-schizophrenia
#17
Meng-Lin Li, Yelena Gulchina, Sarah A Monaco, Bo Xing, Brielle R Ferguson, Yan-Chun Li, Feng Li, Xi-Quan Hu, Wen-Jun Gao
Schizophrenia (SCZ) is a neurodevelopmental psychiatric disorder, in which cognitive function becomes disrupted at early stages of the disease. Although the mechanisms underlying cognitive impairments remain unclear, N-methyl-D-aspartate receptors (NMDAR) hypofunctioning in the prefrontal cortex (PFC) has been implicated. Moreover, cognitive symptoms in SCZ are usually unresponsive to treatment with current antipsychotics and by onset, disruption of the dopamine system, not NMDAR hypofunctioning, dominates the symptoms...
February 16, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28203226/microbial-anti-inflammatory-molecule-mam-from-faecalibacterium-prausnitzii-shows-a-protective-effect-on-dnbs-and-dss-induced-colitis-model-in-mice-through-inhibition-of-nf-%C3%AE%C2%BAb-pathway
#18
Natalia M Breyner, Cristophe Michon, Cassiana S de Sousa, Priscilla B Vilas Boas, Florian Chain, Vasco A Azevedo, Philippe Langella, Jean M Chatel
Faecalibacterium prausnitzii and its supernatant showed protective effects in different chemically-induced colitis models in mice. Recently, we described 7 peptides found in the F. prausnitzii supernatant, all belonging to a protein called Microbial Anti-inflammatory Molecule (MAM). These peptides were able to inhibit NF-κB pathway in vitro and showed anti-inflammatory properties in vivo in a DiNitroBenzene Sulfate (DNBS)-induced colitis model. In this current proof we tested MAM effect on NF-κB pathway in vivo, using a transgenic model of mice producing luciferase under the control of NF-κB promoter...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28199092/application-of-a-quantitative-lc-ms-multiattribute-method-for-monitoring-site-specific-glycan-heterogeneity-on-a-monoclonal-antibody-containing-two-n-linked-glycosylation-sites
#19
Tian Wang, Lily Chu, Wenzhou Li, Ken Lawson, Izydor Apostol, Tamer Eris
A significant challenge of traditional glycan mapping techniques is that they do not provide site-specific glycosylation information. Therefore, for proteins containing multiple glycosylation sites, the individual glycan species present at a particular site cannot be differentiated from those species present at the other glycosylation sites on the molecule. Quantification of glycoform has previously been demonstrated using a multiattribute method (MAM), which can quantify multiple post-translational modifications including deamidation, oxidation, glycosylation variants, and fragmentation ( Rogers, R...
February 27, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28154412/superresolution-imaging-identifies-that-conventional-trafficking-pathways-are-not-essential-for-endoplasmic-reticulum-to-outer-mitochondrial-membrane-protein-transport
#20
Kyle Salka, Shivaprasad Bhuvanendran, Kassandra Wilson, Petros Bozidis, Mansi Mehta, Kristin Rainey, Hiromi Sesaki, George H Patterson, Jyoti K Jaiswal, Anamaris M Colberg-Poley
Most nuclear-encoded mitochondrial proteins traffic from the cytosol to mitochondria. Some of these proteins localize at mitochondria-associated membranes (MAM), where mitochondria are closely apposed with the endoplasmic reticulum (ER). We have previously shown that the human cytomegalovirus signal-anchored protein known as viral mitochondria-localized inhibitor of apoptosis (vMIA) traffics from the ER to mitochondria and clusters at the outer mitochondrial membrane (OMM). Here, we have examined the host pathways by which vMIA traffics from the ER to mitochondria and clusters at the OMM...
December 2017: Scientific Reports
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