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https://www.readbyqxmd.com/read/28231522/novel-2-3-disubstituted-quinazoline-4-3h-one-molecules-derived-from-amino-acid-linked-sulphonamide-as-a-potent-malarial-antifolates-for-dhfr-inhibition
#1
Tarosh S Patel, Satish F Vanparia, Urmila H Patel, Ritu B Dixit, Chaitanya J Chudasama, Bhavesh D Patel, Bharat C Dixit
An optimization of a modified Grimmel's method for N-heterocyclization of Leucine linked sulphonamide leading to 2,3-disustituted-4-quinazolin-(3H)-ones was accomplished. Further, nineteen hybrid quinazolinone motifs (5a-5s) were synthesized by N-heterocyclization reaction under microwave irradiation using TEAA (IL) as green solvent as well as catalyst. The in vitro screening of the hybrid entities against the plasmodium species P. falciparum yielded five antimalarial potent molecules 5g, 5l, 5m, 5n &5p owing comparable activity to the reference drugs...
February 13, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28230786/sex-specificity-of-mineralocorticoid-target-gene-expression-during-renal-development-and-long-term-consequences
#2
Laurence Dumeige, Caroline Storey, Lyvianne Decourtye, Melanie Nehlich, Christophe Lhadj, Say Viengchareun, Laurent Kappeler, Marc Lombès, Laetitia Martinerie
Sex differences have been identified in various biological processes, including hypertension. The mineralocorticoid signaling pathway is an important contributor to early arterial hypertension, however its sex-specific expression has been scarcely studied, particularly with respect to the kidney. Basal systolic blood pressure (SBP) and heart rate (HR) were measured in adult male and female mice. Renal gene expression studies of major players of mineralocorticoid signaling were performed at different developmental stages in male and female mice using reverse transcription quantitative PCR (RT-qPCR), and were compared to those of the same genes in the lung, another mineralocorticoid epithelial target tissue that regulates ion exchange and electrolyte balance...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28230028/leucine-rich-repeats-and-immunoglobulin-like-domains-protein-1-and-fascin-actin-bundling-protein-1-expression-in-nonsmall-cell-lung-cancer
#3
Juanjuan Zhang, Xiaoyan Wang, Yijie Zhang, Jingcan Wu, Nannan Zhou
OBJECTIVE: To assess the clinical significance of leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) and fascin actin-bundling protein 1 (Fascin-1) expression in nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: Six-one NSCLC patients were included in this study. The expression of LRIG1 and Fascin-1 was assayed in the tumor tissue and relative normal lung tissue of the 61 NSCLC patients by immunohistochemistry. The relationship between LRIG1, Fascin-1 expression pattern and lung cancer patients' clinical pathology characteristics was evaluated...
December 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28228936/genetic-basis-of-benzimidazole-resistance-in-teladorsagia-circumcincta-in-ireland
#4
Jason D Keegan, Barbara Good, Theo de Waal, June Fanning, Orla M Keane
Resistance to benzimidazole (BZ) anthelmintics is common in ovine nematodes of economic importance. Single nucleotide polymorphisms (SNP) at three positions in the isotype 1 β- tubulin gene have been associated with BZ resistance and molecular tests for the detection of BZ resistance have been developed. In order to determine if such tests are practicable in Ireland the polymorphisms associated with BZ resistance must be identified. To this end, BZ-resistant nematodes were recovered from four farms in Ireland...
2017: Irish Veterinary Journal
https://www.readbyqxmd.com/read/28228732/c-terminus-methionene-specifically-involved-in-binding-corn-odorants-to-odorant-binding-protein4-in-macrocentrus-cingulum
#5
Tofael Ahmed, Tiantao Zhang, Zhenying Wang, Kanglai He, Shuxiong Bai
The soluble carrier proteins, OBPs carry odor components through sensilium lymph to specific receptors within the antennal sensilla to trigger behavioral responses. Herein, McinOBP4 was characterized from the Macrocentrus cingulum, which is the specialist parasitic insect of Ostrinia furnacalis for better understanding of olfactory recognition mechanism of this wasp. The classical odorant binding protein McinOBP4 showed good binding affinity to corn green leaf volatiles. RT-qPCR results showed that the McinOBP4 was primarily expressed in male and female wasp antennae, with transcripts levels differing by sex...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28226265/alterations-of-ubiquitin-related-proteins-in-the-pathology-and-development-of-schizophrenia-evidence-from-human-and-animal-studies
#6
Jessica L Andrews, Frederic J Goodfellow, Natalie Matosin, Mollie K Snelling, Kelly A Newell, Xu-Feng Huang, Francesca Fernandez-Enright
Gene expression analyses in post-mortem schizophrenia brains suggest that a number of ubiquitin proteasome system (UPS) genes are associated with schizophrenia; however the status of UPS proteins in the schizophrenia brain is largely unknown. Ubiquitin related proteins are inherently involved in memory, neuronal survival and morphology, which are processes implicated in neurodevelopmental disorders such as schizophrenia. We examined levels of five UPS proteins (Protein Inhibitor of Activated STAT2 [PIAS2], F-Box and Leucine rich repeat protein 21 [FBXL21], Mouse Double Minute 2 homolog [MDM2], Ubiquitin Carboxyl-Terminal Hydrolase-L1 [UCHL1] and Ubiquitin Conjugating Enzyme E2D1 [UBE2D1]) involved in these neuronal processes, within the dorsolateral prefrontal cortex of post-mortem schizophrenia subjects and matched controls (n = 30/group), in addition to across neurodevelopmental time-points (juvenile, adolescent and adult stages of life), utilizing a well-established neurodevelopmental phencyclidine (PCP) animal model of schizophrenia...
January 18, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28225256/analysis-and-control-of-chain-mobility-in-protein-hydrogels
#7
Peter B Rapp, Ahmad K Omar, Jeff J Shen, Maren E Buck, Zhen-Gang Wang, David A Tirrell
Coiled-coil domains can direct the assembly of protein block copolymers into physically crosslinked, viscoelastic hydrogels. Here we describe the use of fluorescence recovery after photobleaching (FRAP) to probe chain mobility in reversible hydrogels assembled from engineered proteins bearing terminal coiled-coil domains. We show that chain mobility can be related to the underlying dynamics of the coiled-coil domains by application of a 3-state "hopping" model of chain migration. We further show that genetic programming allows the effective mobility of network chains to be varied 500-fold through modest changes in protein sequence...
February 22, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28223686/metabolic-profiling-of-presymptomatic-huntington-s-disease-sheep-reveals-novel-biomarkers
#8
Debra J Skene, Benita Middleton, Cara K Fraser, Jeroen L A Pennings, Timothy R Kuchel, Skye R Rudiger, C Simon Bawden, A Jennifer Morton
The pronounced cachexia (unexplained wasting) seen in Huntington's disease (HD) patients suggests that metabolic dysregulation plays a role in HD pathogenesis, although evidence of metabolic abnormalities in HD patients is inconsistent. We performed metabolic profiling of plasma from presymptomatic HD transgenic and control sheep. Metabolites were quantified in sequential plasma samples taken over a 25 h period using a targeted LC/MS metabolomics approach. Significant changes with respect to genotype were observed in 89/130 identified metabolites, including sphingolipids, biogenic amines, amino acids and urea...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28222251/prognostic-methylation-markers-for-overall-survival-in-cytogenetically-normal-patients-with-acute-myeloid-leukemia-treated-on-swog-trials
#9
Xiaoyu Qu, Megan Othus, Jerry Davison, Yu Wu, Liying Yan, Soheil Meshinchi, Fabiana Ostronoff, Elihu H Estey, Jerry P Radich, Harry P Erba, Frederick R Appelbaum, Min Fang
BACKGROUND: Aberrant DNA methylation is known to occur in patients with acute myeloid leukemia (AML), whereas methylation signatures and prognostic markers have been proposed. The objective of the current study was to evaluate all CpG sites of the genome and identify prognostic methylation markers for overall survival in patients with AML with normal karyotype (AML-NK). METHODS: AML-NK samples from 7 SWOG trials were analyzed using a novel genome-wide approach called "CHARMcox" (comprehensive high-throughput array-based relative methylation analysis combined with the Cox proportional hazards model) controlling for known clinical covariates...
February 21, 2017: Cancer
https://www.readbyqxmd.com/read/28220423/leeix2-interactors-analysis-and-eix-mediated-responses-measurement
#10
Meirav Leibman-Markus, Silvia Schuster, Adi Avni
Plant-pathogen interactions involve a large number of wide regulatory systems, necessary for plant defense responses against pathogen attack. The fungal protein ethylene-inducing xylanase (EIX) elicits defense responses in specific cultivars of tobacco and tomato. The response to EIX is controlled by a single locus encoding for LeEIX2, a leucine-rich-repeat receptor-like-protein (LRR-RLP). As an RLP, LeEIX2 does not possess an obvious cytoplasmic signaling moiety such as a kinase domain. To study LeEIX2 mode of action, it is essential to identify the potential interactors involved after EIX perception...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28220415/analysis-for-protein-glycosylation-of-pattern-recognition-receptors-in-plants
#11
Takaakira Inokuchi, Yusuke Saijo
Recognition of molecules typical of microbes or aberrant cellular states, termed microbe- or danger-associated molecular patterns (MAMPs/DAMPs), respectively, provides an important step in plant and animal innate immunity. In plants, pattern recognition receptors (PRRs) identified to date are limited to membrane-associated proteins, of which the majority has an extracellular leucine-rich repeat (LRR) or lysine-motif (LysM) domain. These PRRs undergo quality control (QC) in the Endoplasmic Reticulum (ER) that is dependent on Asn (N)-linked glycosylation (Glc3Man9GlcNAc2 conjugation) of their extracellular domain...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28219935/novel-insights-into-gastric-cancer-methylation-of-r-spondins-and-regulation-of-lgr5-by-sp1
#12
Franziska Wilhelm, Eva Simon, Christine Boger, Hans-Michael Behrens, Sandra Kruger, Christoph Rocken
: Recently it was shown that leucine-rich repeat-containing receptor 5 (LGR5) expressing stem cells are the cellular origin of intestinal-type gastric cancer. The aim of our study was to uncover regulatory mechanisms of LGR5 expression in gastric mucosa and their implications for cancer development. Reporter assays identified a LGR5 promoter fragment, which is highly relevant for active LGR5 expression. Chromatin immunoprecipitation (ChIP) verified that SP1 is bound within this region and reporter activity increased in SP1 transfected cells...
February 20, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28219719/cysteine-deprivation-prevents-induction-of-peroxisome-proliferator-activated-receptor-gamma-2-and-adipose-differentiation-of-3t3-l1-cells
#13
Nadia Nabil Haj-Yasein, Ole Berg, Fredrik Jernerén, Helga Refsum, Hilde I Nebb, Knut Tomas Dalen
Plasma cysteine is strongly associated with body fat mass in human cohorts and diets low in cysteine prevents fat accumulation in mice. It is unclear if plasma cysteine affects fat development or if fat accumulation raises plasma cysteine. To determine if cysteine affects adipogenesis, we differentiated 3T3-L1 preadipocytes in medium with reduced cysteine. Cells incubated in media with 10-20μM cysteine exhibited reduced capacity to differentiate into triacylglycerol-storing mature adipocytes compared with cells incubated with 50μM cysteine...
February 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28218415/reduced-penetrance-of-leucine-rich-repeat-kinase-2-mutations-discovering-genetic-factors-of-endogenous-disease-protection
#14
Alexander Balck, Christine Klein
No abstract text is available yet for this article.
February 20, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28216958/-1-h-nmr-based-serum-metabolomics-reveals-erythromycin-induced-liver-toxicity-in-albino-wistar-rats
#15
Atul Rawat, Durgesh Dubey, Anupam Guleria, Umesh Kumar, Amit K Keshari, Swati Chaturvedi, Anand Prakash, Sudipta Saha, Dinesh Kumar
INTRODUCTION: Erythromycin (ERY) is known to induce hepatic toxicity which mimics other liver diseases. Thus, ERY is often used to produce experimental models of drug-induced liver-toxicity. The serum metabolic profiles can be used to evaluate the liver-toxicity and to further improve the understanding of underlying mechanism. OBJECTIVE: To establish the serum metabolic patterns of Erythromycin induced hepatotoxicity in albino wistar rats using (1)H NMR based serum metabolomics...
October 2016: Journal of Pharmacy & Bioallied Sciences
https://www.readbyqxmd.com/read/28215822/structural-and-functional-analysis-of-two-small-leucine-rich-repeat-proteoglycans-fibromodulin-and-chondroadherin
#16
Patricia Paracuellos, Sebastian Kalamajski, Arkadiusz Bonna, Dominique Bihan, Richard W Farndale, Erhard Hohenester
The small leucine-rich proteoglycans (SLRPs) are important regulators of extracellular matrix assembly and cell signalling. We have determined crystal structures at ~2.2 Å resolution of human fibromodulin and chondroadherin, two collagen-binding SLRPs. Their overall fold is similar to that of the prototypical SLRP, decorin, but unlike decorin neither fibromodulin nor chondroadherin forms a stable dimer. A previously identified binding site for integrin α2β1 maps to an α-helix in the C-terminal cap region of chondroadherin...
February 16, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28215742/identification-of-grass-carp-ctenopharyngodon-idella-xbp1s-as-a-primary-member-in-er-stress
#17
Xiangqin Wang, Yichuan Mi, Bin Zhong, Huiling Mao, Yiqi Wan, Tao Zhang, Haizhou Wang, Chengyu Hu
X-box binding protein 1 (XBP1), a vital basic leucine zipper transcription factor for the related gene transcription in endoplasmic reticulum (ER) stress, belongs to the CREB/ATF family. In mammals, XBP1S is the activated one of XBP1 isoform. In order to study the role of fish XBP1S, we cloned and identified the XBP1S (KU509247) from grass carp (Ctenopharyngodon idella) (named CiXBP1S) by homologous cloning and RACE technique. The full length of CiXBP1S is 1694 bp along with 124 bp of 5' UTR, 418 bp of 3' UTR and the longest open reading frame (1152 bp) encoding a polypeptide of 383 amino acids with a well conserved DNA binding domain (BRLZ domain)...
February 16, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28215482/enzymatic-characterization-of-clinical-and-environmental-cryptococcus-neoformans-strains-isolated-in-italy
#18
Gabriella Pini, Elisabetta Faggi, Enza Campisi
BACKGROUND: Cryptococcus neoformans is an encapsulated yeast causing mainly opportunistic infections. The virulence factors involved in cryptococcosis pathogenesis include the presence and the size of the polysaccharide capsule, the production of melanin by phenoloxidase, the growth at 37°C and the enzyme secretion like proteinase, phospholipase and urease. Many other enzymes are secreted by C. neoformans but their role in the fungus virulence is not yet known. AIMS: In order to investigate this topic, we compared the phospholipase production between strains from patients and from bird droppings, and we examined its relationship to phenoloxidase production...
February 16, 2017: Revista Iberoamericana de Micología
https://www.readbyqxmd.com/read/28215032/nlrp3-inflammasome-activation-regulated-by-nf-%C3%AE%C2%BAb-and-dapk-contributed-to-paraquat-induced-acute-kidney-injury
#19
Zhenning Liu, Xiaokai Wang, Yu Wang, Min Zhao
Paraquat can result in dysfunction of multiple organs after ingestion in human. However, the mechanisms of nucleotide-binding domain and leucine-rich repeat containing protein 3 (NLRP3) inflammasome activation in acute kidney injury have not been clearly demonstrated. The aim of this study was to determine the effect of NLRP3 inflammasome activation and its regulation by nuclear factor-kappa B (NF-κB) and death-associated protein kinase (DAPK). Male Wistar rats were treated with intraperitoneal injection of paraquat at 20 mg/kg, and NF-κB inhibitor BAY 11-7082 was pretreated at 10 mg/kg 1 h before paraquat exposure...
February 18, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28214755/identification-of-a-new-tert-leucinate-class-synthetic-cannabinoid-in-powder-and-spice-like-herbal-incenses-methyl-2-1-5-fluoropentyl-indole-3-carbonyl-amino-3-3-dimethyl-butanoate-5f-mdmb-pica
#20
Martijn D P Risseeuw, Peter Blanckaert, Vera Coopman, Stijn Van Quekelberghe, Serge Van Calenbergh, Jan Cordonnier
A brown powder and different product packages of "spice-like" herbal incenses were analyzed using a systematic identification approach based on liquid chromatography with diode array detector (HPLC-PDA) and gas chromatography mass spectrometry (GC-MS) with computer based library search against spectral libraries. However, the most predominant compound in the methanolic sample solutions could not be identified. In order to elucidate the chemical structure, a more extensive analysis of the material was initiated using liquid chromatography mass spectrometry (LC-MS), electrospray high resolution mass spectrometry (ESI-HRMS) and (1)H, (13)C and (19)F nuclear magnetic resonance spectroscopy (NMR), which allowed the identification and characterization of the major compound as methyl 2-[[1-(5-fluoropentyl)indole-3-carbonyl]amino]-3,3-dimethyl-butanoate (5F-MDMB-PICA)...
February 4, 2017: Forensic Science International
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