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Mediator And Complex

Bilal Houshaymi, Nadine Nasreddine, Mamdouh Kedees, Zeina Soayfane
The bioavailability of ivermectin is modulated by lipid-based formulations and membrane efflux transporters such as Breast Cancer Resistance Protein and P-glycoprotein (BCRP and P-gp). We have investigated the effect of oleic acid on the uptake of ivermectin in vitro using Caco-2 cells and in vivo in the intestines of wild-type mice. Complex micelles (M) with oleic acid induced a significant increase (e. g. for M3 was 7-fold, p≤0.001) in the uptake of the drug in a time-dependent manner with no involvement of cholesterol in the mechanism...
August 13, 2018: Drug Research
Dasiel O Borroto-Escuela, Alexander O Tarakanov, Ismel Brito, Kjell Fuxe
The existence of mGluR, NMDAR, AMPAR and putative KAR heteroreceptor complexes in synaptic and extrasynaptic regions of brain glutamate synapses represents a major integrative mechanism. Our aim in the current article is to analyze if the formation of the different types glutamate hetereceptor complexes involves the contribution of triplet amino acid homologies (protriplets) in a postulated receptor interface based on the triplet puzzle theory. Seven main sets (lists) of receptor pairs in databases were used containing various sets (lists) of human receptor heteromers and nonheteromers obtained from the available scientific publications including the publically available GPCR-hetnet database...
April 11, 2018: Pharmacological Reports: PR
N Dimasi, R Fleming, H Wu, C Gao
In recent years, bispecific antibodies (BisAbs) have emerged as novel pharmaceutical candidates owing to their ability to engage two disease mediators simultaneously, thus providing a possible alternative therapeutic approach in complex diseases such as cancer and inflammation. Here we provide an overview of the molecular design, recombinant expression in mammalian cells and purification of BisAbs based on full-length IgG-scFv formats. Practical considerations and strategies to optimize transient expression and purification are also discussed...
August 10, 2018: Methods: a Companion to Methods in Enzymology
Jialu Zhao, Xu Liu, Chunyue Huo, Tian Zhao, Haihong Ye
MK-801, a non-competitive NMDA receptor antagonist, disturbs NMDA receptor function in rodents and induces psychological and behavioral changes similar to schizophrenia (SCZ). However, the effects of MK-801 treatment on gene expression are largely unknown. Here we performed RNA-sequencing on the prefrontal cortex of MK-801-exposed male mice in order to analyze gene expression and co-expression patterns related to SCZ and to identify mechanisms that underlie the molecular etiology of this disorder. Transcriptome analysis revealed that the differentially expressed genes were more often associated with biological processes that included postsynaptic transmission, immune system process, response to external stimulus and hemostasis...
August 10, 2018: Neuroscience
Xiaojing Wang, Marcelle Ribeiro, Arvin Iracheta-Vellve, Patrick Lowe, Aditya Ambade, Abhishek Satishchandran, Terence Bukong, Donna Catalano, Karen Kodys, Gyongyi Szabo
Inflammatory cell activation drives diverse cellular programming during hepatic diseases. Hypoxia-inducible factors (HIFs) have recently been identified as important regulators of immunity and inflammation. In non-alcoholic steatohepatitis (NASH), HIF-1α is upregulated in hepatocytes where it induces steatosis; however, the role of HIF-1α in macrophages under metabolic stress has not been explored. In this study, we found increased HIF-1α levels in hepatic macrophages in methionine-choline-deficient (MCD) diet-fed mice and in macrophages of NASH patients compared to controls...
August 13, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Wenfei Song, Miao Gui, Xinquan Wang, Ye Xiang
The trimeric SARS coronavirus (SARS-CoV) surface spike (S) glycoprotein consisting of three S1-S2 heterodimers binds the cellular receptor angiotensin-converting enzyme 2 (ACE2) and mediates fusion of the viral and cellular membranes through a pre- to postfusion conformation transition. Here, we report the structure of the SARS-CoV S glycoprotein in complex with its host cell receptor ACE2 revealed by cryo-electron microscopy (cryo-EM). The complex structure shows that only one receptor-binding domain of the trimeric S glycoprotein binds ACE2 and adopts a protruding "up" conformation...
August 13, 2018: PLoS Pathogens
Katie Beadon, Raquel Guimarães-Costa, Jean-Marc Léger
PURPOSE OF REVIEW: Multifocal motor neuropathy (MMN) has specific clinical and electrophysiologic features but can be difficult to diagnose if cases are not typical. Intravenous immunoglobulin (IVIg) remains the core initial and long-term treatment. In this review, recent advances in the diagnosis, monitoring and treatment of MMN are discussed. RECENT FINDINGS: The pathology of MMN likely depends on immune-mediated attack of the nodes of Ranvier and paranodal regions leading to conduction block...
August 9, 2018: Current Opinion in Neurology
Ayyappasamy Sudalaiyadum Perumal, Rishi Kishore Vishwakarma, Yangbo Hu, Zakia Morichaud, Konstantin Brodolin
The transcriptional activator RbpA associates with Mycobacterium tuberculosis RNA polymerase (MtbRNAP) during transcription initiation, and stimulates formation of the MtbRNAP-promoter open complex (RPo). Here, we explored the influence of promoter motifs on RbpA-mediated activation of MtbRNAP containing the stress-response σB subunit. We show that both the 'extended -10' promoter motif (T-17G-16T-15G-14) and RbpA stabilized RPo and allowed promoter opening at suboptimal temperatures. Furthermore, in the presence of the T-17G-16T-15G-14 motif, RbpA was dispensable for RNA synthesis initiation, while exerting a stabilization effect on RPo...
August 8, 2018: Nucleic Acids Research
Donghyun Ka, Dong Man Jang, Byung Woo Han, Euiyoung Bae
Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins provide microbial adaptive immunity against invading foreign nucleic acids. In type II-A CRISPR-Cas systems, the Cas1-Cas2 integrase complex and the subtype-specific Csn2 comprise the CRISPR adaptation module, which cooperates with the Cas9 nuclease effector for spacer selection. Here, we report the molecular organization of the Streptococcus pyogenes type II-A CRISPR adaptation module and its interaction with Cas9 via Csn2...
August 8, 2018: Nucleic Acids Research
Pucharee Songprakhon, Thawornchai Limjindaporn, Guey Chuen Perng, Chunya Puttikhunt, Thanawat Thaingtamtanha, Thanyaporn Dechtawewat, Sawanan Saitornuang, Chairat Uthaipibull, Sissades Thongsima, Pa-Thai Yenchitsomanus, Prida Malasit, Sansanee Noisakran
Virus-host interactions play important roles in virus infection and host cellular response. Several viruses, including dengue virus (DENV), usurp host chaperones to support their amplification and survival in the host cell. We investigated the interaction of nonstructural protein 1 (NS1) of DENV with three endoplasmic reticulum-resident chaperones (i.e. GRP78, calnexin and calreticulin) to delineate their functional roles and potential binding sites for protein complex formation. GRP78 protein showed prominent association with DENV NS1 in virus-infected Huh7 cells as evidenced by co-localization and co-immunoprecipitation assays...
August 10, 2018: Journal of General Virology
Kohei Uematsu, Takaaki Ueno, Hajime Katano
ε-Poly-L-lysine (εPL) is a homopolymer of L-lysine residues with linkages between the α-carboxyl and ε-amino groups. εPL exists as a polycationic species under acidic and neutral conditions, and can form a polyion complex with negatively charged glucose oxidase (GOx). We previously reported that εPL significantly promoted a GOx enzymatic reaction using ferricyanide ion ([Fe(CN)6 ]3- ) as the oxidant. Here, we construct a GOx-immobilized electrode using εPL and glutaraldehyde, and show that [Fe(CN)6 ]3- can efficiently act as the mediator in this electrode...
2018: Analytical Sciences: the International Journal of the Japan Society for Analytical Chemistry
J F Felix, C A M Cecil
Epigenetic changes represent a potential mechanism underlying associations of early-life exposures and later life health outcomes. Population-based cohort studies starting in early life are an attractive framework to study the role of such changes. DNA methylation is the most studied epigenetic mechanism in population research. We discuss the application of DNA methylation in early-life population studies, some recent findings, key challenges and recommendations for future research. Studies into DNA methylation within the Developmental Origins of Health and Disease framework generally either explore associations between prenatal exposures and offspring DNA methylation or associations between offspring DNA methylation in early life and later health outcomes...
August 13, 2018: Journal of Developmental Origins of Health and Disease
Zhi Liu, Xin He, Lili Wang, Yunhua Zhang, Yue Hai, Rui Gao
This review summarizes the current research status of hepatotoxicity and points out that drug induced liver injury (DILI) remains an important scientific problem that urgently needs to be solved. Due to the special nature of Chinese Herbal medicine and the complexity of its clinical use, it is difficult to identify and evaluate its toxicity and resulting herb induced liver injury (HILI). At the same time, due to a lack of specific indicators, the direct and indirect long-term effects of Chinese Herbal Medicine on the liver are also difficult to be clinically determined...
August 13, 2018: Current Drug Metabolism
S S Panteleev, I B Sivachenko, O A Lyubashina
BACKGROUND: Buspirone, a partial agonist of the 5-HT1a receptor (5-HT1a R), owing to potential antinociceptive properties may be useful in treatment of abdominal pain in IBS patients. The pain-related effects of buspirone are mediated via the 5-HT1a Rs, specifically located within the ventrolateral medulla (VLM). The most animal studies of the 5-HT1a R involvement in pain control have been carried out with somatic behavioral tests. The 5-HT1a R contribution in visceral pain transmission within the VLM is unclear...
August 13, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Cheng Xiong, Dan Luo, Aihua Lin, Chunli Zhang, Libo Shan, Ping He, Bo Li, Qiaomei Zhang, Bin Hua, Zilv Yuan, Hanxia Li, Junhong Zhang, Changxian Yang, Yongen Lu, Zhibiao Ye, Taotao Wang
Carotenoids play important roles in many biological processes, such as light harvesting, photoprotection and visual attraction in plants. However, the regulation of carotenoid biosynthesis is still not fully understood. Here, we demonstrate that SlBBX20, a B-box (BBX) zinc-finger transcription factor, is a positive regulator of carotenoid accumulation in tomato (Solanum lycopersicum). Overexpression of SlBBX20 leads to dark green fruits and leaves and higher levels of carotenoids relative to the wild-type. Interactions between SlBBX20 and DE-ETIOLATED 1 (SlDET1) lead to the ubiquitination and 26S proteasome-mediated degradation of SlBBX20...
August 13, 2018: New Phytologist
Yuliang Yang, Guo Lihua, Zhenzhen Tian, Xicheng Liu, Yuteng Gong, Hongmei Zheng, Xingxing Ge, Zhe Liu
A family of novel imine-N-heterocyclic carbene ruthenium(II) complexes of the general formula [(η6-p-cymene)Ru(C^N)Cl]PF6- (where C^N is imine-N-heterocyclic carbene chelating ligand with varying substituents) have been prepared and characterized. In this imine-N-heterocyclic carbene chelating ligand framework, there are three potential sites that can be modified, which distinguishes this class of ligand and provides a body of flexibilities and opportunities to tune the cytotoxicity of these ruthenium(II) complexes...
August 12, 2018: Chemistry, An Asian Journal
Francois Brial, Aurélie Le Lay, Marc-Emmanuel Dumas, Dominique Gauguier
Evidence from the literature keeps highlighting the impact of mutualistic bacterial communities of the gut microbiota on human health. The gut microbita is a complex ecosystem of symbiotic bacteria which contributes to mammalian host biology by processing, otherwise, indigestible nutrients, supplying essential metabolites, and contributing to modulate its immune system. Advances in sequencing technologies have enabled structural analysis of the human gut microbiota and allowed detection of changes in gut bacterial composition in several common diseases, including cardiometabolic disorders...
August 12, 2018: Cellular and Molecular Life Sciences: CMLS
Panagiotis Lymperopoulos, Joseph Msanne, Roel Rabara
Being sessile organisms, plants need to continually adapt and modulate their rate of growth and development in accordance with the changing environmental conditions, a phenomenon referred to as plasticity. Plasticity in plants is a highly complex process that involves a well-coordinated interaction between different signaling pathways, the spatiotemporal involvement of phytohormones and cues from the environment. Though research studies are being carried out over the years to understand how plants perceive the signals from changing environmental conditions and activate plasticity, such remain a mystery to be resolved...
2018: Frontiers in Plant Science
Xueling Ma, Zhongjun Chen, Le Wang, Gesheng Wang, Zihui Wang, XiaoBo Dong, Binyu Wen, Zhichen Zhang
A substantial knowledge on the pathogenesis of diabetes mellitus (DM) by oxidative stress and inflammation is available. Berberine is a biologically active botanical that can combat oxidative stress and inflammation and thus ameliorate DM, especially type 2 DM. This article describes the potential of berberine against oxidative stress and inflammation with special emphasis on its mechanistic aspects. In diabetic animal studies, the modified levels of proinflammatory cytokines and oxidative stress markers were observed after administering berberine...
2018: Frontiers in Pharmacology
Masashi Minamino, Shoin Tei, Lumi Negishi, Masato T Kanemaki, Atsunori Yoshimura, Takashi Sutani, Masashige Bando, Katsuhiko Shirahige
Sister chromatid cohesion, mediated by cohesin, is required for accurate chromosome segregation [1, 2]. This process requires acetylation of cohesin subunit SMC3 by evolutionarily conserved cohesin acetyltransferases: Eco1 in budding yeast; XEco1 and XEco2 in Xenopus; and ESCO1 and ESCO2 in human [3-10]. Eco1 is recruited to chromatin through physical interaction with PCNA [11] and is degraded by the Skp1/Cul1/F-box protein complex after DNA replication to prevent ectopic cohesion formation [12]. In contrast, XEco2 recruitment to chromatin requires prereplication complex formation [13] and is degraded by the anaphase-promoting complex (APC) [14]...
August 1, 2018: Current Biology: CB
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