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I Porreca, L Ulloa-Severino, P Almeida, D Cuomo, A Nardone, G Falco, M Mallardo, C Ambrosino
Several studies associate foetal human exposure to bisphenol A (BPA) to metabolic/endocrine diseases, mainly diabesity. They describe the role of BPA in the disruption of pancreatic beta cell, adipocyte and hepatocyte functions. Indeed, the complexity of the diabesity phenotype is due to the involvement of different endoderm-derived organs, all targets of BPA. Here, we analyse this point delineating a picture of different mechanisms of BPA toxicity in endoderm-derived organs leading to diabesity. Moving from epidemiological data, we summarize the in vivo experimental data of the BPA effects on endoderm-derived organs (thyroid, pancreas, liver, gut, prostate and lung) after prenatal exposure...
October 24, 2016: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
Kimona Issa, Todd P Pierce, Chukwuweieke Gwam, Peter Goljan, Anthony Festa, Anthony J Scillia, Michael A Mont
Airport security measures continue to be updated with the incorporation of the new body scanners and automatic target recognition software. The purpose of this study was analyze the incidence of: (1) triggering the security alarm; (2) extra security searches; (3) perceived inconvenience; and (4) presence of other surgical hardware in those who underwent total knee arthroplasty (TKA) and passed through airport security. A questionnaire was given to 125 consecutive patients with a TKA. Those who passed through airport security after January 2014 were considered for inclusion...
October 24, 2016: Journal of Knee Surgery
Kaihang Wang, Julius Fredens, Simon F Brunner, Samuel H Kim, Tiongsun Chia, Jason W Chin
Synthetic recoding of genomes, to remove targeted sense codons, may facilitate the encoded cellular synthesis of unnatural polymers by orthogonal translation systems. However, our limited understanding of allowed synonymous codon substitutions, and the absence of methods that enable the stepwise replacement of the Escherichia coli genome with long synthetic DNA and provide feedback on allowed and disallowed design features in synthetic genomes, have restricted progress towards this goal. Here we endow E. coli with a system for efficient, programmable replacement of genomic DNA with long (>100-kb) synthetic DNA, through the in vivo excision of double-stranded DNA from an episomal replicon by CRISPR/Cas9, coupled to lambda-red-mediated recombination and simultaneous positive and negative selection...
October 24, 2016: Nature
Jingjing Wu, Mingzhi Zhang, Delong Liu
The Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has been approved for the treatment of chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. Acquired resistance to ibrutinib due to BTK C481S mutation has been reported. Mutations in PLCγ2 can also mediate resistance to ibrutinib. Untoward effects due to off-target effects are also disadvantages of ibrutinib. More selective and potent BTK inhibitors (ACP-196, ONO/GS-4059, BGB-3111, CC-292) are being investigated. This review summarized the preclinical research and clinical data of ONO/GS-4059...
October 20, 2016: Oncotarget
Sinead Toomey, Stephen F Madden, Simon J Furney, Yue Fan, Mark McCormack, Carragh Stapleton, Mattia Cremona, Gianpiero L Cavalleri, Malgorzata Milewska, Naomi Elster, Aoife Carr, Joanna Fay, Elaine W Kay, Susan Kennedy, John Crown, William M Gallagher, Bryan T Hennessy, Alex J Eustace
BACKGROUND: Trastuzumab treatment for women with HER2-positive breast cancer (BC) resulted in the significant improvement of both relapse free survival (RFS) and overall survival (OS). However, many women who are classified as HER2-positive do not respond. Many studies have focused on the role of somatic mutations rather than germline polymorphisms in trastuzumab resistance. RESULTS: We completed an Agena MassArray screen of 10 ERBB-family single nucleotide polymorphisms (SNPs) in 194 adjuvant trastuzumab treated HER2-positive BC patients...
October 20, 2016: Oncotarget
Jinfeng Kong, Juan Du, Yunling Wang, Mingzi Yang, Jianchao Gao, Xiaofan Wei, Weigang Fang, Jun Zhan, Hongquan Zhang
Kindlin-1, an integrin-interacting protein, has been implicated in TGF-β/Smad3 signaling. However, the molecular mechanism underlying Kindlin-1 regulation of TGF-β/Smad3 signaling remains elusive. Here, we reported that Kindlin-1 is an important mediator of TGF-β/Smad3 signaling by showing that Kindlin-1 physically interacts with TGF-β receptor I (TβRI), Smad anchor for receptor activation (SARA) and Smad3. Kindlin-1 is required for the interaction of Smad3 with TβRI, Smad3 phosphorylation, nuclear translocation, and finally the activation of TGF-β/Smad3 signaling pathway...
October 20, 2016: Oncotarget
Cole R Drifka, Agnes G Loeffler, Kara Mathewson, Adib Keikhosravi, Jens C Eickhoff, Yuming Liu, Sharon M Weber, W John Kao, Kevin W Eliceiri
Risk factors for pancreatic ductal adenocarcinoma (PDAC) progression after surgery are unclear, and additional prognostic factors are needed to inform treatment regimens and therapeutic targets. PDAC is characterized by advanced sclerosis of the extracellular matrix, and interactions between cancer cells, fibrillar collagen, and other stromal components play an integral role in progression. Changes in stromal collagen alignment have been shown to modulate cancer cell behavior and have important clinical value in other cancer types, but little is known about its role in PDAC and prognostic value...
October 20, 2016: Oncotarget
Lourdes Mateos-Hernández, Margarita Villar, Ernesto Doncel-Pérez, Marco Trevisan-Herraz, Ángel García-Forcada, Francisco Romero Ganuza, Jesús Vázquez, José de la Fuente
Guillain-Barré syndrome (GBS) is an autoimmune-mediated peripheral neuropathy of unknown cause. However, about a quarter of GBS patients have suffered a recent bacterial or viral infection, and axonal forms of the disease are especially common in these patients. Proteomics is a good methodological approach for the discovery of disease biomarkers. Until recently, most proteomics studies of GBS and other neurodegenerative diseases have focused on the analysis of the cerebrospinal fluid (CSF). However, serum represents an attractive alternative to CSF because it is easier to sample and has potential for biomarker discovery...
October 20, 2016: Oncotarget
Mijung Kwon, Jae-Hoon Kim, Yevangelina Rybak, Alex Luna, Chel Hun Choi, Joon-Yong Chung, Stephen M Hewitt, Asha Adem, Elizabeth Tubridy, Juan Lin, Steven K Libutti
Filamin A interacting protein 1-like (FILIP1L) is an inhibitor of the canonical WNT pathway. WNT/β-catenin signaling and its downstream pathway, epithelial-to-mesenchymal transition (EMT), play a key role in ovarian cancer metastasis and chemoresistance. To study the clinical implications of FILIP1L in regulating the WNT/β-catenin pathway, the expression of FILIP1L, β-catenin, SNAIL and SLUG was analyzed by immunohistochemistry on tissue microarrays of 369 ovarian samples ranging from normal to metastatic...
October 20, 2016: Oncotarget
Lorenz Jahn, Dirk M van der Steen, Renate S Hagedoorn, Pleun Hombrink, Michel G D Kester, Marjolein P Schoonakker, Daniëlle de Ridder, Peter A van Veelen, J H Frederik Falkenburg, Mirjam H M Heemskerk
Immunotherapy of B-cell leukemia and lymphoma with CD20-targeting monoclonal antibodies (mAbs) has demonstrated clinical efficacy. However, the emergence of unresponsive disease due to low or absent cell surface CD20 urges the need to develop additional strategies. In contrast to mAbs, T-cells via their T-cell receptor (TCR) can recognize not only extracellular but also intracellular antigens in the context of HLA molecules. We hypothesized that T-cells equipped with high affinity CD20-targeting TCRs would be able to recognize B-cell malignancies even in the absence of extracellular CD20...
October 20, 2016: Oncotarget
J R Griswold, D G Medvedev, J W Engle, R Copping, J M Fitzsimmons, V Radchenko, J C Cooley, M E Fassbender, D L Denton, K E Murphy, A C Owens, E R Birnbaum, K D John, F M Nortier, D W Stracener, L H Heilbronn, L F Mausner, S Mirzadeh
Actinium-225 and (213)Bi have been used successfully in targeted alpha therapy (TAT) in preclinical and clinical research. This paper is a continuation of research activities aiming to expand the availability of (225)Ac. The high-energy proton spallation reaction on natural thorium metal targets has been utilized to produce millicurie quantities of (225)Ac. The results of sixteen irradiation experiments of thorium metal at beam energies between 78 and 192MeV are summarized in this work. Irradiations have been conducted at Brookhaven National Laboratory (BNL) and Los Alamos National Laboratory (LANL), while target dissolution and processing was carried out at Oak Ridge National Laboratory (ORNL)...
September 28, 2016: Applied Radiation and Isotopes
Jinbin Yuan, Yang Chen, Jian Liang, Chong-Zhi Wang, Xiaofei Liu, Zhihong Yan, Yi Tang, Jiankang Li, Chun-Su Yuan
Ginseng is one of the most widely used natural medicines in the world. Recent studies have suggested Panax ginseng has a wide range of beneficial effects on aging, central nervous system disorders, and neurodegenerative diseases. However, knowledge about the specific bioactive components of ginseng is still limited. This work aimed to screen for the bioactive components in Panax ginseng that act against neurodegenerative diseases, using the target cell-based bioactivity screening method. Firstly, component analysis of Panax ginseng extracts was performed by UPLC-QTOF-MS, and a total of 54 compounds in white ginseng were characterized and identified according to the retention behaviors, accurate MW, MS characteristics, parent nucleus, aglycones, side chains, and literature data...
October 17, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Guang-Hui Ma, Yan Ye, Dan Zhang, Xin Xu, Pei Si, Jian-Long Peng, Yong-Long Xiao, Rui-Yuan Cao, Yu-Ling Yin, Jing Chen, Lin-Xiang Zhao, Yu Zhou, Wu Zhong, Hong Liu, Xiao-Min Luo, Li-Li Chen, Xu Shen
Hand, foot and mouth disease (HFMD) is a serious, highly contagious disease. HFMD caused by Enterovirus 71 (EV71), results in severe complications and even death. The pivotal role of EV71 3C(pro) in the viral life cycle makes it an attractive target for drug discovery and development to treat HFMD. In this study, we identified novel EV71 3C(pro) inhibitors by docking-based virtual screening. Totally 50 compounds were selected to test their inhibitory activity against EV71 3C(pro). The best inhibitor DC07090 exhibited the inhibition potency with an IC50 value of 21...
October 11, 2016: European Journal of Medicinal Chemistry
Zhuofeng Yu, Pinjing He, Liming Shao, Hua Zhang, Fan Lü
Since municipal solid waste (MSW) landfill harbours miscellaneous wastes, pollutants and microorganisms, it gradually becomes a huge potential reservoir for breeding antibiotic resistance genes (ARGs). The objective of this study was to determine the prevalence and diversity of ARGs associated with various mobile genetic elements (MGEs) in MSW landfill leachates. The relationship of ARGs with leachate characteristics was also studied to explore the influence of landfill age. Seven sulfonamides (sulfapyridine, sulfadiazine, sulfathiazole, sulfamethoxazole, sulfamerazine, sulfamethazine and sulfaquinoxaline), three encoded ARGs (sul-I, sul-II and sul-III) and four types of MGEs (plasmids, transposons, integrons and insertion sequences) were quantified in leachates with landfill ages ranging from 3 months-6 years...
October 18, 2016: Water Research
A C Sampaio, R J Mendes, P G Castro, A M Silva
Solid lipid nanoparticles (SLNs) are used as carriers for drug delivery, and are high biocompatible and designed to endure in the host organism. Despite its current industrial production is low, many of these substances are available on the market, and much more are in the production pipeline. As a result, many of them will end in aquatic systems raising the question whether they can pose a risk to aquatic biota and the associated ecological processes. Microbial decomposers of plant litter, play a key role in forested streams being responsible for the energy flow between terrestrial and aquatic environments...
October 21, 2016: Ecotoxicology and Environmental Safety
Jing Liu, Dujuan Zhao, Wenxiu He, Huiyuan Zhang, Zhonghao Li, Yuxia Luan
The anti-leukemia effect of cytarabine (Ara-C) is severely restricted by its high hydrophilic properties and rapid plasma degradation. Herein, a novel amphiphilic small molecular prodrug of Ara-C was developed by coupling a short aliphatic chain, hexanoic acid (HA) to 4-NH2 of the parent drug. Based on the amphiphilic nature, the resulting bioconjugate (HA-Ara) could spontaneously self-assemble into stable spherical nanoassemblies (NAs) with an extremely high drug loading (∼71wt%). Moreover, folate receptor (FR)-targeting NAs with high grafting efficient folic acid - bovine serum albumin (FA-BSA) conjugate immobilized on the surface (NAs/FA-BSA) was prepared...
October 19, 2016: Journal of Colloid and Interface Science
Money Gupta, Rashi Chauhan, Yamuna Prasad, Gulshan Wadhwa, Chakresh Kumar Jain
The lack of complete treatments and appearance of multiple drug-resistance strains of Burkholderia cepacia complex (Bcc) are causing an increased risk of lung infections in cystic fibrosis patients. Bcc infection is a big risk to human health and demands an urgent need to identify new therapeutics against these bacteria. Network biology has emerged as one of the prospective hope in identifying novel drug targets and hits. We have applied protein-protein interaction methodology to identify new drug-target candidates (orthologs) in Burkhloderia cepacia GG4, which is an important strain for studying the quorum-sensing phenomena...
October 8, 2016: Computational Biology and Chemistry
Sterling L Karakula, Roger D Weiss, Margaret L Griffin, Allison M Borges, Allen J Bailey, R Kathryn McHugh
BACKGROUND: Among those with opioid use disorder, heroin use is associated with poorer prognosis relative to use of prescription opioids alone. However, relatively little is known about distinguishing features between those who use heroin relative to those who use prescription opioids. In the present study we evaluated differences in delay discounting in those with opioid use disorder based on primary opioid of use. Delay discounting is associated with a range of negative outcomes and is an important therapeutic target in this population...
October 17, 2016: Drug and Alcohol Dependence
G Besson, G Barragan-Jason, S J Thorpe, M Fabre-Thorpe, S Puma, M Ceccaldi, E J Barbeau
Verifying that a face is from a target person (e.g. finding someone in the crowd) is a critical ability of the human face processing system. Yet how fast this can be performed is unknown. The 'entry-level shift due to expertise' hypothesis suggests that - since humans are face experts - processing faces should be as fast - or even faster - at the individual than at superordinate levels. In contrast, the 'superordinate advantage' hypothesis suggests that faces are processed from coarse to fine, so that the opposite pattern should be observed...
October 21, 2016: Cognition
Penelope Anne Lynch, Mike Boots
Evolution persistently undermines vector control programs through insecticide resistance. Here we propose a novel strategy which instead exploits evolution to generate and sustain new control tools. Effective spatial repellents are needed to keep vectors out of houses. Our approach generates such new repellents by combining a high-toxicity insecticide with a candidate repellent initially effective against only part of the vector population. By killing mosquitoes that enter treated properties the insecticide selects for vector phenotypes deflected by the repellent, increasing efficacy of the repellent against the target vector population and in turn protecting the insecticide against the spread of insecticide resistance...
October 25, 2016: ELife
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