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https://www.readbyqxmd.com/read/29339431/molecular-insights-into-function-and-competitive-inhibition-of-pseudomonas-aeruginosa-multiple-virulence-factor-regulator
#1
Tomoe Kitao, Francois Lepine, Seda Babloudi, Frederick Walte, Stefan Steinbacher, Klaus Maskos, Michael Blaesse, Michele Negri, Michael Pucci, Bob Zahler, Antonio Felici, Laurence G Rahme
New approaches to antimicrobial drug discovery are urgently needed to combat intractable infections caused by multidrug-resistant (MDR) bacteria. Multiple virulence factor regulator (MvfR or PqsR), a Pseudomonas aeruginosa quorum sensing transcription factor, regulates functions important in both acute and persistent infections. Recently identified non-ligand-based benzamine-benzimidazole (BB) inhibitors of MvfR suppress both acute and persistent P. aeruginosa infections in mice without perturbing bacterial growth...
January 16, 2018: MBio
https://www.readbyqxmd.com/read/29334982/genome-wide-identification-characterization-and-classification-of-ionotropic-glutamate-receptor-genes-iglurs-in-the-malaria-vector-anopheles-sinensis-diptera-culicidae
#2
Ting-Ting Wang, Feng-Ling Si, Zheng-Bo He, Bin Chen
BACKGROUND: Ionotropic glutamate receptors (iGluRs) are conserved ligand-gated ion channel receptors, and ionotropic receptors (IRs) were revealed as a new family of iGluRs. Their subdivision was unsettled, and their characteristics are little known. Anopheles sinensis is a major malaria vector in eastern Asia, and its genome was recently well sequenced and annotated. METHODS: We identified iGluR genes in the An. sinensis genome, analyzed their characteristics including gene structure, genome distribution, domains and specific sites by bioinformatic methods, and deduced phylogenetic relationships of all iGluRs in An...
January 15, 2018: Parasites & Vectors
https://www.readbyqxmd.com/read/29306369/can-placing-lead-rubber-inferolateral-to-the-light-beam-diaphragm-limit-ionising-radiation-to-multiple-radiosensitive-organs
#3
C Hayre, H Bungay, C Jeffery, C Cobb, J Atutornu
INTRODUCTION: This article investigates a practical method of reducing the impact of scattered radiation during a lateral radiographic projection of the elbow. The light beam diaphragm (LBD) is generally accepted to limit ionising radiation using horizontal and longitudinal lead shutters, yet this article evidences further dose limitation by placing lead-rubber inferolateral to the LBD device. METHODS: Using an anthropomorphic phantom and arm construction scattered radiation was recorded at multiple radiosensitive organs...
February 2018: Radiography
https://www.readbyqxmd.com/read/29298820/hbt1-a-novel-ampa-receptor-potentiator-with-lower-agonistic-effect-avoided-bell-shaped-response-in-in-vitro-bdnf-production
#4
Akiyoshi Kunugi, Yasukazu Tajima, Haruhiko Kuno, Satoshi Sogabe, Haruhide Kimura
Alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor (AMPA-R) potentiators with brain-derived neurotrophic factor (BDNF)-induction potential could be promising as therapeutic drugs for neuropsychiatric and neurological disorders. However, AMPA-R potentiators such as LY451646 have risks of narrow bell-shaped responses in pharmacological effects, including in vivo BDNF induction. Interestingly, LY451646 and LY451395, other AMPA-R potentiators, showed agonistic effects and exhibited bell-shaped responses in the BDNF production in primary neurons...
January 3, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29278715/accumulation-of-beta-synuclein-in-cortical-neurons-is-associated-with-autophagy-attenuation-in-the-brains-of-dementia-with-lewy-body-patients
#5
Tracey Evans, Wai Ling Kok, Katrina Cowan, Megan Hefford, Oleg Anichtchik
Dementia with Lewy bodies (DLB) is the second most prevalent neurodegenerative dementia, where an accumulation of aggregated fibrillar alpha-synuclein in neurons of limbic and forebrain regions of the brain leads to visual hallucination, cognitive impairment of a fluctuating nature and extrapyramidal motor disturbances. Beta-synuclein counteracts aggregation of alpha-synuclein in vitro and in animal models, however it is not clear whether this effect occurs in human Lewy body dementia (LBD) diseases. Here we examine expression of alpha-, beta-synuclein and autophagy markers in the frontal cortex (BA9) and occipital cortex (BA18-19) of patients with neuropathologically confirmed DLB/LBD and age-matched controls...
December 23, 2017: Brain Research
https://www.readbyqxmd.com/read/29277173/novel-tool-selection-in-left-brain-damaged-patients-with-apraxia-of-tool-use-a-study-of-three-cases
#6
François Osiurak, Marine Granjon, Isabelle Bonnevie, Joël Brogniart, Laura Mechtouff, Amandine Benoit, Norbert Nighoghossian, Mathieu Lesourd
OBJECTIVES: Recent evidence indicates that some left brain-damaged (LBD) patients have difficulties to use familiar tools because of the inability to reason about physical object properties. A fundamental issue is to understand the residual capacity of those LBD patients in tool selection. METHODS: Three LBD patients with tool use disorders, three right brain-damaged (RBD) patients, and six matched healthy controls performed a novel tool selection task, consisting in extracting a target out from a box by selecting the relevant tool among eight, four, or two tools...
December 26, 2017: Journal of the International Neuropsychological Society: JINS
https://www.readbyqxmd.com/read/29249935/loss-of-neuroprotective-factors-in-neurodegenerative-dementias-the-end-or-the-starting-point
#7
REVIEW
Luisa Benussi, Giuliano Binetti, Roberta Ghidoni
Recent clinical, genetic and biochemical experimental evidences highlight the existence of common molecular pathways underlying neurodegenerative diseases. In this review, we will explore a key common pathological mechanism, i.e., the loss of neuroprotective factors, across the three major neurodegenerative diseases leading to dementia: Alzheimer's disease (AD), Frontotemporal dementia (FTD) and Lewy body dementia (LBD). We will report evidences that the Brain Derived Neurotrophic Factor (BDNF), the most investigated and characterized brain neurotrophin, progranulin, a multi-functional adipokine with trophic and growth factor properties, and cystatin C, a neuroprotective growth factor, are reduced in AD, FTD, and LBD...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29249286/neurotransmitter-funneling-optimizes-glutamate-receptor-kinetics
#8
Alvin Yu, Héctor Salazar, Andrew J R Plested, Albert Y Lau
Ionotropic glutamate receptors (iGluRs) mediate neurotransmission at the majority of excitatory synapses in the brain. Little is known, however, about how glutamate reaches the recessed binding pocket in iGluR ligand-binding domains (LBDs). Here we report the process of glutamate binding to a prototypical iGluR, GluA2, in atomistic detail using unbiased molecular simulations. Charged residues on the LBD surface form pathways that facilitate glutamate binding by effectively reducing a three-dimensional diffusion process to a spatially constrained, two-dimensional one...
December 12, 2017: Neuron
https://www.readbyqxmd.com/read/29243081/a-novel-dmapp-responding-genetic-circuit-sensor-for-high-throughput-screening-and-evolving-isoprene-synthase
#9
Chun-Li Liu, Jing-Yi Cai, Hao-Ran Bi, Tian-Wei Tan
High-throughput screening is a popular tool for collating biological data which would otherwise require the use of excessive resources. In this study, an artificial genetic circuit sensor responding to dimethylallyl diphosphate (DMAPP) was constructed based on a modified L-arabinose operon for high-throughput screening and isoprene synthase (ispS) evolution in Escherichia coli (E. coli). As a first step, the DNA sequence of the L-arabinose ligand-binding domain (LBD) was replaced with an ispS gene to enable the AraC operon responding to DMAPP, which is the substrate of the IspS enzyme...
December 14, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29240340/update-on-current-care-guideline-memory-disorders
#10
(no author information available yet)
Any complaint about memory should be examined. Diagnosis is based on international criteria. Basic evaluation consists of medical history, clinical evaluation, cognitive tests and brain imaging. When a diagnosis of Alzheimer's disease (AD), AD with cerebrovascular disease or with Lewy Body disease (LBD), or Dementia associated with Parkinson's disease or LBD is made, evidence-based medical therapy (acetylcholine esterase inhibitor or memantine) is indicated as a part of comprehensive care. In frontotemporal degenerations, these drugs are ineffective...
2017: Duodecim; Lääketieteellinen Aikakauskirja
https://www.readbyqxmd.com/read/29227192/coiled-coil-motif-in-lbd16-and-lbd18-transcription-factors-are-critical-for-dimerization-and-biological-function-in-arabidopsis
#11
Shashank K Pandey, Jungmook Kim
The LATERAL ORGAN BOUNDARIES (LOB) DOMAIN (LBD) gene family members encode a class of plant-specific transcription factors that play important roles in many different aspects of plant growth and development. The LBD proteins contain a conserved LOB domain harboring a Leu zipper-like coiled-coil motif, which has been predicted to mediate protein-protein interactions among the LBD family members. Dimerization of transcription factors is crucial for the modulation of their DNA-binding affinity, specificity, and diversity, contributing to the transcriptional regulation of distinct cellular and biological responses...
December 11, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/29219065/transactivation-assays-that-identify-indirect-and-direct-activators-of-human-pregnane-x-receptor-pxr-nr1i2-and-constitutive-androstane-receptor-car-nr1i3
#12
Marija Pinne, Elsa Ponce, Judy L Raucy
BACKGROUND: Nuclear receptors (NRs), including PXR and CAR, are presumed to be ligand-dependent transcription factors, but ligand binding is not an absolute requirement for activation. Indeed, many compounds activate PXR and CAR by indirect mechanisms. Detecting these indirect activators of specific nuclear receptors in vitro has been difficult. As NR activation of either or both PXR and CAR can lead to drug-drug interactions and adverse drug effects, false negatives obtained with screening tools incapable of detecting indirect activators could present liabilities...
December 6, 2017: Drug Metabolism Letters
https://www.readbyqxmd.com/read/29215899/tool-use-in-left-brain-damaged-patients-difficulties-in-reasoning-but-not-in-estimating-the-physical-properties-of-objects
#13
Alexandrine Faye, Sophie Jacquin-Courtois, François Osiurak
OBJECTIVE: The purpose of this study was to deepen our understanding of the cognitive bases of human tool use based on the technical reasoning hypothesis (i.e., the reasoning-based approach). This approach assumes that tool use is supported by the ability to reason about an object's physical properties (e.g., length, weight, strength, etc.) to perform mechanical actions (e.g., lever). In this framework, an important issue is to understand whether left-brain-damaged (LBD) individuals with tool-use deficits are still able to estimate the physical object's properties necessary to use the tool...
December 7, 2017: Neuropsychology
https://www.readbyqxmd.com/read/29203903/structures-of-ppar%C3%AE-complexed-with-lobeglitazone-and-pioglitazone-reveal-key-determinants-for-the-recognition-of-antidiabetic-drugs
#14
Min A Lee, Lingchen Tan, Huiseon Yang, Yeong-Gwan Im, Young Jun Im
Peroxisome proliferator-activator receptor (PPAR) γ is a nuclear hormone receptor that regulates glucose homeostasis, lipid metabolism, and adipocyte function. PPARγ is a target for thiazolidinedione (TZD) class of drugs which are widely used for the treatment of type 2 diabetes. Recently, lobeglitazone was developed as a highly effective TZD with reduced side effects by Chong Kun Dang Pharmaceuticals. To identify the structural determinants for the high potency of lobeglitazone as a PPARγ agonist, we determined the crystal structures of the PPARγ ligand binding domain (LBD) in complex with lobeglitazone and pioglitazone at 1...
December 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29203584/fc-independent-immune-thrombocytopenia-via-mechanomolecular-signaling-in-platelets
#15
M Edward Quach, Matthew A Dragovich, Wenchun Chen, Anum K Syed, Wenpeng Cao, Xin Liang, Wei Deng, Simon F De Meyer, Guangheng Zhu, Jun Peng, Heyu Ni, Carolyn M Bennett, Ming Hou, Jerry Ware, Hans Deckmyn, X Frank Zhang, Renhao Li
Immune thrombocytopenia (ITP) is a prevalent autoimmune disease characterized by autoantibody-induced platelet clearance. Some ITP patients are refractory to standard immunosuppressive treatments such as intravenous immunoglobulin (IVIG). These patients often have autoantibodies targeting the ligand-binding domain (LBD) of glycoprotein (GP)Ibα, a major subunit of the platelet mechanoreceptor complex GPIb-IX. However, the molecular mechanism of this Fc-independent platelet clearance is not clear. Here, we report that many anti-LBD monoclonal antibodies such as 6B4, but not AK2, activated GPIb-IX in a shear-dependent manner and induced IVIG-resistant platelet clearance in mice...
December 4, 2017: Blood
https://www.readbyqxmd.com/read/29191565/magnetic-resonance-imaging-correlates-of-left-bundle-branch-disease-in-patients-with-nonischemic-cardiomyopathy
#16
Chrysanthos Grigoratos, Riccardo Liga, Elena Bennati, Andrea Barison, Giancarlo Todiere, Giovanni Donato Aquaro, Matteo Dell'Omodarme, Michele Emdin, Pier Giorgio Masci
The pathologic correlates of intraventricular conduction delays in patients with nonischemic cardiomyopathy (NIC) have been scarcely investigated. We assessed left ventricular (LV) structural, functional, and tissue abnormalities associated with intraventricular conduction left bundle disease (LBD), including left anterior hemiblock or complete left bundle branch block, in a cohort of patients with NIC submitted to cardiovascular magnetic resonance. Twelve-lead electrocardiogram and cardiovascular magnetic resonance were performed in 196 consecutive patients with NIC...
November 6, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/29185101/association-between-traditional-clinical-high-risk-features-and-gene-expression-profile-classification-in-uveal-melanoma
#17
Brandon T Nguyen, Ryan S Kim, Maria E Bretana, Eric Kegley, Amy C Schefler
PURPOSE: To evaluate the association between traditional clinical high-risk features of uveal melanoma patients and gene expression profile (GEP). METHODS: This was a retrospective, single-center, case series of patients with uveal melanoma. Eighty-three patients met inclusion criteria for the study. Patients were examined for the following clinical risk factors: drusen/retinal pigment epithelium (RPE) changes, vascularity on B-scan, internal reflectivity on A-scan, subretinal fluid (SRF), orange pigment, apical tumor height/thickness, and largest basal dimensions (LBD)...
November 28, 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/29184030/arabidopsis-atxr2-deposits-h3k36me3-at-the-promoters-of-lbd-genes-to-facilitate-cellular-dedifferentiation
#18
Kyounghee Lee, Ok-Sun Park, Pil Joon Seo
Cellular dedifferentiation, the transition of differentiated somatic cells to pluripotent stem cells, ensures developmental plasticity and contributes to wound healing in plants. Wounding induces cells to form a mass of unorganized pluripotent cells called callus at the wound site. Explanted cells can also form callus tissues in vitro. Reversible cellular differentiation-dedifferentiation processes in higher eukaryotes are controlled mainly by chromatin modifications. We demonstrate that ARABIDOPSIS TRITHORAX-RELATED 2 (ATXR2), a histone lysine methyltransferase that promotes the accumulation of histone H3 proteins that are trimethylated on lysine 36 (H3K36me3) during callus formation, promotes early stages of cellular dedifferentiation through activation of LATERAL ORGAN BOUNDARIES DOMAIN (LBD) genes...
November 28, 2017: Science Signaling
https://www.readbyqxmd.com/read/29182104/steered-molecular-dynamics-for-studying-ligand-unbinding-of-ecdysone-receptor
#19
Xueping Hu, Song Hu, Jiazhe Wang, Yawen Dong, Li Zhang, Yanhong Dong
Ecdysone receptor (EcR) is an important target for pesticide design. Ligand binding regulates EcR transcriptional activity similar to other nuclear receptors; however, the pathways by which ligands enter and leave the EcR remain poorly understood. Here, we performed computational studies to identify unbinding pathways of an ecdysone agonist [the selective ecdysone agonist, BYI06830] from the EcR ligand binding domain (EcR LBD). BYI06830 can dissociate from EcR LBD via four different pathways with little effect on receptor structure...
November 28, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29170008/genetic-control-of-root-system-development-in-maize
#20
REVIEW
Frank Hochholdinger, Peng Yu, Caroline Marcon
The maize root system comprises structurally and functionally different root types. Mutant analyses have revealed that root-type-specific genetic regulators intrinsically determine the maize root system architecture. Molecular cloning of these genes has demonstrated that key elements of auxin signal transduction, such as LOB domain (LBD) and Aux/IAA proteins, are instrumental for seminal, shoot-borne, and lateral root initiation. Moreover, genetic analyses have demonstrated that genes related to exocytotic vesicle docking, cell wall loosening, and cellulose synthesis and organization control root hair elongation...
November 20, 2017: Trends in Plant Science
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