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Rag da Silva, C P Churchward, A V Karlyshev, O Eleftheriadou, A K Snabaitis, M R Longman, A Ryan, R Griffin
BACKGROUND AND PURPOSE: The level of cell surface expression of the meningococcal vaccine antigen, Factor H binding protein (FHbp) varies between and within strains and this limits the breadth of strains that can be targeted by FHbp-based vaccines. The molecular pathway dictating expression of FHbp at the cell surface, including its lipidation, sorting to the outer membrane and export, and the potential regulation of this pathway have not been investigated until now. This knowledge will aid our evaluation of FHbp vaccines...
October 26, 2016: British Journal of Pharmacology
Li Cheng, Jun Zhang, Xin-Yi Li, Li Yuan, Yan-Fang Pan, Xiao-Rong Chen, Tian-Ming Gao, Jian-Tian Qiao, Jin-Shun Qi
Amyloid β protein (Aβ) plays a critical role in pathogenesis of Alzheimer's disease (AD). Our previous studies indicated that the sequence 31-35 in Aβ molecule is an effective active center responsible for Aβ neurotoxicity in vivo and in vitro. In the present study, we prepared a novel antibody specifically targeting the sequence 31-35 of amyloid β protein, and investigated the neuroprotection of the anti-Aβ31-35 antibody against Aβ1-42 -induced impairments in neuronal viability, spatial memory, and hippocampal synaptic plasticity in rats...
October 26, 2016: Hippocampus
J B Hinrichs, T Werncke, T Kaireit, M M Hoeper, K M Olsson, J C Kamp, F K Wacker, F Bengel, C von Falck, I Schatka, B C Meyer
Purpose: To determine if C-Arm computed tomography (CACT) has added diagnostic value in patients suffering from chronic thromboembolic pulmonary hypertension (CTEPH) with a positive mismatch pattern in ventilation/perfusion single photon emission computed tomography (V/Q SPECT). Materials and Methods: 28 patients (23 men, 5 women, 62 ± 18 years) with CTEPH who had undergone SPECT, followed by CACT and right heart catheterization (RHC) were included. Two independent readers reviewed SPECT and CACT. Findings indicating CTEPH and their location (segmental or sub-segmental) were identified (V/Q mismatch in SPECT and vascular pathologies in CACT)...
October 26, 2016: RöFo: Fortschritte Auf Dem Gebiete der Röntgenstrahlen und der Nuklearmedizin
Carrie D Patnode, Michelle L Henninger, Caitlyn A Senger, Leslie A Perdue, Evelyn P Whitlock
Importance: Although 80% of infants in the United States start breastfeeding, only 22% are exclusively breastfed up to around 6 months as recommended by a number of professional organizations. Objective: To systematically review the evidence on the benefits and harms of breastfeeding interventions to support the US Preventive Services Task Force in updating its 2008 recommendation. Data Sources: MEDLINE, PubMed, Cumulative Index for Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, and PsycINFO for studies published in the English language between January 1, 2008, and September 25, 2015...
October 25, 2016: JAMA: the Journal of the American Medical Association
Ji Yi, Zhen Puyang, Liang Feng, Lian Duan, Peiji Liang, Vadim Backman, Xiaorong Liu, Hao F Zhang
Purpose: Elastic light backscattering spectroscopy (ELBS) has exquisite sensitivity to the ultrastructural properties of tissue and thus has been applied to detect various diseases associated with ultrastructural alterations in their early stages. This study aims to test whether ELBS can detect early damage in retinal ganglion cells (RGCs). Methods: We used a mouse model of partial optic nerve crush (pONC) to induce rapid RGC death. We confirmed RGC loss by axon counting and characterized the changes in retinal morphology by optical coherence tomography (OCT) and in retinal function by full-field electroretinogram (ERG), respectively...
October 1, 2016: Investigative Ophthalmology & Visual Science
Dawna Lewis, Kendra Schmid, Samantha O'Leary, Jody Spalding, Elizabeth Heinrichs-Graham, Robin High
Purpose: This study examined the effects of stimulus type and hearing status on speech recognition and listening effort in children with normal hearing (NH) and children with mild bilateral hearing loss (MBHL) or unilateral hearing loss (UHL). Method: Children (5-12 years of age) with NH (Experiment 1) and children (8-12 years of age) with MBHL, UHL, or NH (Experiment 2) performed consonant identification and word and sentence recognition in background noise. Percentage correct performance and verbal response time (VRT) were assessed (onset time, total duration)...
October 25, 2016: Journal of Speech, Language, and Hearing Research: JSLHR
Chen-Xu Ni, Yang Qi, Jin Zhang, Ying Liu, Wei-Heng Xu, Jing Xu, Hong-Gang Hu, Qiu-Ye Wu, Yan Wang, Jun-Ping Zhang
The eradication of cancer stem cells (CSCs) is significant for cancer therapy and prevention. In this study, we evaluated WM130, a novel derivative of matrine, for its effect on CSCs using human hepatocellular carcinoma (HCC) cell lines, their sphere cells, and sorted EpCAM+ cells. We revealed that WM130 could not only inhibit proliferation and colony formation of HCC cells, but also suppress the expression of some stemness-related genes and up-regulate some mature hepatocyte marker genes, indicating a promotion of differentiation from CSCs to hepatocytes...
October 22, 2016: Oncotarget
Jian Xie, Yan Feng, Ting Lin, Xiao-Yu Huang, Rui-Huan Gan, Yong Zhao, Bo-Hua Su, Lin-Can Ding, Lin She, Jiang Chen, Li-Song Lin, Xu Lin, Da-Li Zheng, You-Guang Lu
The cadherin-4 gene (CDH4) of the cadherin family encodes non-epithelial R-cadherin (R-cad); however, the function of this gene in different types of cancer remains controversial. In this study, we found higher expression of CDH4 mRNA in a salivary adenoid cystic carcinoma (SACC) cell line with low metastatic potential (SACC-83) than in a cell line with high metastatic potential (SACC-LM). By analyzing 67 samples of SACC tissues and 40 samples of paraneoplastic normal tissues, we found R-cad highly expressed in 100% of normal paraneoplastic tissue but only expressed in 64% of SACC tumor tissues (P<0...
October 22, 2016: Oncotarget
Bo Yang, Shiming Zhang, Zhihao Wang, Chunxu Yang, Wen Ouyang, Fuxiang Zhou, Yunfeng Zhou, Conghua Xie
β-catenin is a crucial signal transduction molecule in the Wnt/β-catenin signal pathway, and increased β-catenin expression has consistently been found in high grade gliomas. However, the mechanisms responsible for β-catenin overexpression have remained elusive. Here we show that the deubiquitinase USP9X stabilizes β-catenin and thereby promotes high grade glioma cell growth. USP9X binds β-catenin and removes the Lys 48-linked polyubiquitin chains that normally mark β-catenin for proteasomal degradation...
October 22, 2016: Oncotarget
Cinthia C Stempin, Claudia C Motrán, María P Aoki, Cristian R Falcón, Fabio M Cerbán, Laura Cervi
Macrophage plasticity is critical for controlling inflammation including those produced by helminth infections, where alternatively activated macrophages (AAM) are accumulated in tissues. AAM expressing the co-inhibitory molecule programmed death ligand 2 (PD-L2), which is capable of binding programmed death 1 (PD-1) expressed on activated T cells, have been demonstrated in different parasitic infections. However, the role of PD-L2 during F. hepatica infection has not yet been explored. We observed that F. hepatica infection or a F...
October 21, 2016: Oncotarget
Ju Hui Jeong, Yong Jin Oh, Yunmee Lho, Sun You Park, Kwang-Hyeon Liu, Eunyoung Ha, Young Ho Seo
The molecular chaperone Hsp90 plays an important role in cancer cell survival and proliferation by regulating the maturation and stabilization of numerous oncogenic proteins. Due to its potential to simultaneously disable multiple signaling pathways, Hsp90 has emerged as an attractive therapeutic target for cancer treatment. In this study, the design, synthesis, and biological evaluation of a series of Hsp90 inhibitors are described. Among the synthetic compounds, 6,7-dihydrothieno [3,2-c]pyridin-5(4H)-yl amide 19 exhibits a remarkable binding affinity to the N-terminus of Hsp90 in a fluorescence polarization (FP) binding assay (IC50 = 50...
October 18, 2016: European Journal of Medicinal Chemistry
Timothy J Ritchie, Simon J F Macdonald
The impact of replacing a mono-substituted benzene (phenyl) ring with thirty three aromatic and nine aliphatic heterocycles on nine ADME-related screens (solubility, lipophilicity, permeability, protein binding CYP450 inhibition and metabolic clearance) was assessed using matched molecular pair analysis. The results indicate that the influence on the ADME profile can differ significantly depending on the ring identity and importantly on the individual regioisomers that are possible for some rings. This information enables the medicinal chemist to make an informed choice about which rings and regioisomers to employ as mono-substituted benzene replacements, based upon the knowledge of how such replacements are likely to influence ADME-related parameters, for example to target higher solubility whilst avoiding CYP450 liabilities...
October 15, 2016: European Journal of Medicinal Chemistry
Begüm Nurpelin Sağlık, Sinem Ilgın, Yusuf Özkay
Donepezil (DNP), an acetylcholinesterase (AChE) inhibitor, is one of the most preferred choices in Alzheimer diseases (AD) therapy. In the present study, 38 new DNP analogues were synthesized. Structures of the synthesized compounds (1-38) were elucidated by IR, (1)H NMR, (13)C NMR and HRMS spectroscopic methods and elemental analysis. Inhibitory potential of the compounds on cholinesterase enzymes was investigated. None of the compounds displayed significant activity on butyrylcholinesterase (BChE) enzyme...
October 19, 2016: European Journal of Medicinal Chemistry
Shanshan Li, Wenda Zhang, Yanwei Yang, Ting Ma, Jianpeng Guo, Shanshan Wang, Wenying Yu, Lingyi Kong
Constitutive activation of STAT3 has been found in a wide variety of cancers and demonstrated as a very attractive therapeutic target. Disrupting both acetylation and phosphorylation of STAT3 protein was hypothesized to greatly deactivate STAT3, therefore, treating cancers. To demonstrate the hypothesis, two series of novel resveratrol-caffeic acid hybrids were designed aiming to regulate both acetylation and phosphorylation of STAT3 protein, which is also the first report of the synthetic inhibitors simultaneously regulating two biological reactions of STAT3 to our knowledge...
October 15, 2016: European Journal of Medicinal Chemistry
Anke M Klein, Rianne van Niekerk, Giovanni Ten Brink, Ronald M Rapee, Jennifer L Hudson, Susan M Bögels, Eni S Becker, Mike Rinck
BACKGROUND AND OBJECTIVES: Cognitive theories suggest that cognitive biases may be related and together influence the anxiety response. However, little is known about the interrelations of cognitive bias tasks and whether they allow for an improved prediction of fear-related behavior in addition to self-reports. This study simultaneously addressed several types of cognitive biases in children, to investigate attention bias, interpretation bias, memory bias and fear-related associations, their interrelations and the prediction of behavior...
October 5, 2016: Journal of Behavior Therapy and Experimental Psychiatry
Ling Fu, Tao Huang, Shuo Wang, Xiaohong Wang, Limin Su, Chao Li, Yuanhui Zhao
Although modes of action (MOAs) play a key role in the understanding of the toxic mechanism of chemicals, the MOAs have not been investigated for antibiotics to green algae. This paper is to discriminate excess toxicity from baseline level and investigate the MOAs of 13 different antibiotics to algae by using the determined toxicity values. Comparison of the toxicities shows that the inhibitors of protein synthesis to bacteria, such as azithromycin, doxycycline, florfenicol and oxytetracycline, exhibit significantly toxic effects to algae...
October 23, 2016: Chemosphere
Binbin Fang, Jing Guo, Fuxing Li, John P Giesy, Lianjun Wang, Wei Shi
Industrialized development of the Yangtze River Delta, China, has resulted in larger amounts of wastes, including sludges from treatment of these wastes. Methods to manage and dispose, including reuse were urgently needed. Sludge and reused products were collected from two largest factories, KEYUAN and HENGJIA where treated sludges were turned into bricks or sludge cake to be placed in landfills, respectively. Metals and organic compounds were quantified in sludges and leachates assessed by use of toxicity characterized leaching procedure (TCLP) while acute toxicity was determined by Daphnia magna...
October 23, 2016: Chemosphere
Caterina Gratton, Timothy O Laumann, Evan M Gordon, Babatunde Adeyemo, Steven E Petersen
Humans easily and flexibly complete a wide variety of tasks. To accomplish this feat, the brain appears to subtly adjust stable brain networks. Here, we investigate what regional factors underlie these modifications, asking whether networks are either altered at (1) regions activated by a given task or (2) hubs that interconnect different networks. We used fMRI "functional connectivity" (FC) to compare networks during rest and three distinct tasks requiring semantic judgments, mental rotation, and visual coherence...
October 25, 2016: Cell Reports
Kathia Sandoval, Yan Ding, Piero Gardinali
Comprehensive characterization of exposure media used in toxicology studies is still an area of significant divergence when evaluating potential oil spill impacts. When preparing exposure media used for toxicology testing, small variations in simple parameters such as mixing energy, oil type and loading can significantly affect the concentration of the oil components to which test organisms are exposed. The key goal of this study was compare and contrast the physical and chemical compositions of oil water mixtures prepared using fresh and weathered Macondo-related oils under different conditions of mixing and in the presence/absence of chemical dispersants...
October 23, 2016: Science of the Total Environment
Andrea Fagagnini, Riccardo Montioli, Andra Caloiu, Marc Ribó, Douglas V Laurents, Giovanni Gotte
Bovine pancreatic ribonuclease A (RNase A) is the monomeric prototype of the so-called secretory 'pancreatic-type' RNase super-family. Like the naturally domain-swapped dimeric bovine seminal variant, BS-RNase, and its glycosylated RNase B isoform, RNase A forms N- and C-terminal 3D domain-swapped oligomers after lyophilization from acid solutions, or if subjected to thermal denaturation at high protein concentration. All mentioned RNases can undergo deamidation at Asn67, forming Asp or isoAsp derivatives that modify the protein net charge and consequently its enzymatic activity...
October 23, 2016: Biochimica et Biophysica Acta
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