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https://www.readbyqxmd.com/read/28545850/renal-response-to-intravascular-volume-expansion-in-euvolemic-heart-failure-patients-with-reduced-ejection-fraction-mechanistic-insights-and-clinical-implications
#1
Petra Nijst, Frederik H Verbrugge, Pieter Martens, Matthias Dupont, W H Wilson Tang, Wilfried Mullens
BACKGROUND: Untreated and preclinical heart failure patients with reduced ejection fraction (HFrEF) have an impaired ability to alleviate excess intravascular volume. OBJECTIVES: To investigate 1) the renal response to intravascular volume expansion in euvolemic and optimally treated HFrEF patients and 2) loop diuretic efficiency. METHODS: 14 healthy and 28 HFrEF patients underwent intravascular volume expansion with 1l hydroxyl ethyl starch 6% during 3h after which a loop diuretic was administered...
May 14, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28544098/crystal-structure-of-the-sensor-domain-of-baes-from-serratia-marcescens-fs14
#2
Ya Zhang, Shenshen Qiu, Shanshan Jia, Dongqing Xu, Tingting Ran, Weiwu Wang
The sensor histidine kinases of two-component signal-transduction systems (TCSs) are essential for bacteria to adapt to variable environmental conditions. The two-component regulatory system BaeS/R increases multidrug and metal resistance in Salmonella and Escherichia coli. In this study, we report the X-ray structure of the periplasmic sensor domain of BaeS from Serratia marcescens FS14. The BaeS sensor domain (34-160) adopts a mixed α/β-fold containing a central four-stranded antiparallel β-sheet flanked by a long N-terminal α-helix and additional loops and a short C-terminal α-helix on each side...
May 24, 2017: Proteins
https://www.readbyqxmd.com/read/28542401/molecular-dynamics-analysis-of-the-aggregation-propensity-of-polyglutamine-segments
#3
Jingran Wen, Daniel R Scoles, Julio C Facelli
Protein misfolding and aggregation is a pathogenic feature shared among at least ten polyglutamine (polyQ) neurodegenerative diseases. While solvent-solution interaction is a key factor driving protein folding and aggregation, the solvation properties of expanded polyQ tracts are not well understood. By using GPU-enabled all-atom molecular dynamics simulations of polyQ monomers in an explicit solvent environment, this study shows that solvent-polyQ interaction propensity decreases as the lengths of polyQ tract increases...
2017: PloS One
https://www.readbyqxmd.com/read/28541756/genetic-diversity-of-mtdna-d-loop-sequences-in-four-native-chinese-chicken-breeds
#4
H W Guo, C Li, X N Wang, Z J Li, G R Sun, G X Li, X J Liu, X T Kang, R L Han
1. To explore the genetic diversity of Chinese indigenous chicken breeds, a 585 bp fragment of the mitochondrial DNA (mtDNA) region was sequenced in 102 birds from the Xichuan Black-bone chicken, Yunyang Black-bone chicken and Lushi chicken. In addition, 30 mtDNA D-loop sequences of Silkie fowls were downloaded from NCBI. The mtDNA D-loop sequence polymorphism and maternal origin of 4 chicken breeds were analysed in this study. 2. The results showed that a total of 33 mutation sites and 28 haplotypes were detected in the 4 chicken breeds...
May 25, 2017: British Poultry Science
https://www.readbyqxmd.com/read/28541545/kr%C3%A3-ppel-like-factors-compete-for-promoters-and-enhancers-to-fine-tune-transcription
#5
Melissa D Ilsley, Kevin R Gillinder, Graham W Magor, Stephen Huang, Timothy L Bailey, Merlin Crossley, Andrew C Perkins
Krüppel-like factors (KLFs) are a family of 17 transcription factors characterized by a conserved DNA-binding domain of three zinc fingers and a variable N-terminal domain responsible for recruiting cofactors. KLFs have diverse functions in stem cell biology, embryo patterning, and tissue homoeostasis. KLF1 and related family members function as transcriptional activators via recruitment of co-activators such as EP300, whereas KLF3 and related members act as transcriptional repressors via recruitment of C-terminal Binding Proteins...
May 24, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28539829/multifaceted-regulation-of-gene-expression-by-the-apoptosis-and-splicing-associated-protein-complex-and-its-components
#6
REVIEW
Bhagyashree Deka, Kusum Kumari Singh
The differential deposition of RNA-binding proteins (RBPs) on pre-mRNA mediates the processes of gene expression. One of the complexes containing RBPs that play a crucial part in RNA metabolism is the apoptosis-and splicing-associated protein (ASAP) complex. In this review, we present a summary of the structure of ASAP complex and its localization. Also, we discuss the findings by different groups on various functions of the subunits of the ASAP complex in RNA metabolism. The subunits of the ASAP complex are RNPS1, Acinus and SAP18...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28539416/the-extinction-of-cocaine-seeking-requires-a-window-of-infralimbic-pyramidal-neuron-activity-after-unreinforced-lever-presses
#7
Andrea L Gutman, Kelle E Nett, Caitlin V Cosme, Wensday R Worth, Subhash C Gupta, John A Wemmie, Ryan T LaLumiere
The infralimbic cortex (IL) mediates the extinction learning and active suppression of cocaine-seeking behavior. However, the precise temporal relationship among IL activity, lever pressing, and extinction learning is unclear. To address this issue, we employed activity-guided optogenetics in male Sprague-Dawley rats to optically silence IL pyramidal neurons for 20 s immediately following unreinforced lever presses during early extinction training after cocaine self-administration. Optical inhibition of the IL increased active lever pressing during shortened extinction sessions but did not alter the retention of the extinction learning as assessed in ensuing extinction sessions with no optical inhibition...
May 24, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28539365/functional-analysis-of-human-cytochrome-p450-21a2-variants-involved-in-congenital-adrenal-hyperplasia
#8
Chunxue Wang, Pradeep S Pallan, Wei Zhang, Li Lei, Francis K Yoshimoto, Michael R Waterman, Martin Egli, F Peter Guengerich
Cytochrome P450 (P450, CYP) 21A2 is the major steroid 21-hydroxylase, converting progesterone to 11-deoxycorticosterone and 17α-hydroxy(OH)progesterone to 11-deoxycortisol. More than 100 CYP21A2 variants give rise to congenital adrenal hyperplasia (CAH). We previously reported a structure of wild-type (WT) human P450 21A2 with bound progesterone and now present a structure bound to the other substrate (17α-OH progesterone). We found that the 17α-OH progesterone- and progesterone-bound complex structures are highly similar, with only some minor differences in surface loop regions...
May 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28539250/target-residence-time-guided-optimization-on-ttk-kinase-results-in-inhibitors-with-potent-anti-proliferative-activity
#9
Joost C M Uitdehaag, Jos de Man, Nicole Willemsen-Seegers, Martine B W Prinsen, Marion A A Libouban, Jan Gerard Sterrenburg, Joeri J P de Wit, Judith R F de Vetter, Jeroen A D M de Roos, Rogier C Buijsman, Guido J R Zaman
The protein kinase TTK (Mps1) is a critical component of the spindle assembly checkpoint and a promising drug target for treatment of aggressive cancers, such as triple negative breast cancer. While the first TTK inhibitors have entered clinical trials, little is known about how the inhibition of TTK with small molecule compounds affects cellular activity. We studied the selective TTK inhibitor NTRC 0066-0, which was developed in our own laboratory, together with eleven TTK inhibitors developed by other companies, including Mps-BAY2b, BAY 1161909, BAY 1217389 (Bayer), TC-Mps1-12 (Shionogi), and MPI-0479605 (Myrexis)...
May 21, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28538623/impact-of-a-novel-pi3-kinase-inhibitor-in-preventing-mitochondrial-dna-damage-and-damage-associated-molecular-pattern-accumulation-results-from-the-biochronicity-project
#10
George E Black, Kyle K Sokol, Donald M Moe, Jon Simmons, David Muscat, Victor Pastukh, Gina Capley, Olena Gorodnya, Mykhalo Ruchko, Mark B Roth, Mark Gillespie, Matthew J Martin
BACKGROUND: Despite improvements in the management of severely injured patients, development of multiple organ dysfunction syndrome (MODS) remains a morbid complication of traumatic shock. One of the key attributes of MODS is a profound bioenergetics crisis, for which the mediators and mechanisms are poorly understood. We hypothesized that metabolic uncoupling using an experimental PI3-kinase inhibitor, LY294002 (LY), may prevent mitochondrial abnormalities that lead to the generation of mitochondrial DNA (mtDNA) damage and the release of mtDNA damage associated molecular patterns (DAMPs) METHODS: 16 swine were studied using LY294002 (LY), a non-selective PI3-KI: Animals were assigned to Trauma only (TO, N=3); LY drug only (LYO, N=3); and Experimental (N=10), trauma + drug (LY+T) groups...
May 22, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28536180/yy1-and-ctcf-orchestrate-a-3d-chromatin-looping-switch-during-early-neural-lineage-commitment
#11
Jonathan A Beagan, Michael T Duong, Katelyn R Titus, Linda Zhou, Zhendong Cao, Jingjing Ma, Caroline V Lachanski, Daniel R Gillis, Jennifer E Phillips-Cremins
CTCF is an architectural protein with a critical role in connecting higher-order chromatin folding in pluripotent stem cells. Recent reports have suggested that CTCF binding is more dynamic during development than previously appreciated. Here we set out to understand the extent to which shifts in genome-wide CTCF occupancy contribute to the 3-D reconfiguration of fine-scale chromatin folding during early neural lineage commitment. Unexpectedly, we observe a sharp decrease in CTCF occupancy during the transition from naive/primed pluripotency to multipotent primary neural progenitor cells (NPCs)...
May 23, 2017: Genome Research
https://www.readbyqxmd.com/read/28535045/bet-bromodomain-inhibitors-with-one-step-synthesis-discovered-from-virtual-screen
#12
Alex M Ayoub, Laura M L Hawk, Ryan J Herzig, Jiewei Jiang, Andrea J Wisniewski, Clifford T Gee, Peiliang Zhao, Jin-Yi Zhu, Norbert Berndt, Nana K Offei-Addo, Thomas G Scott, Jun Qi, James E Bradner, Timothy R Ward, Ernst Schönbrunn, Gunda I Georg, William C K Pomerantz
Chemical inhibition of epigenetic regulatory proteins BrdT and Brd4 is emerging as a promising therapeutic strategy in contraception, cancer, and heart disease. We report an easily synthesized dihydropyridopyrmidine pan-BET inhibitor scaffold, which was uncovered via a virtual screen followed by testing in a fluorescence anisotropy assay. Dihydropyridpyimidine 3 was subjected to further characterization and is highly selective for the BET family of bromodomains. Structure-activity relationship data and ligand deconstruction highlight the importance of the substitution of the uracil moiety for potency and selectivity...
May 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28534683/transfer-from-pediatric-to-adult-endocrinology
#13
Marybeth R Jones, Brett W Robbins, Marilyn Augustine, Jackie Doyle, Jean Mack-Fogg, Heather Jones, Patience H White
OBJECTIVE: Adult and pediatric endocrinologists share responsibility for the transition of youth with type 1 diabetes from pediatric to adult healthcare. This study aimed to increase successful transfers to adult care in subspecialty practices by establishing a systematic healthcare transition (HCT) process. METHODS: Providers from the adult and pediatric endocrinology divisions at the University of Rochester Medical Center (URMC) met monthly to customize and integrate the 6 Core Elements (6CEs) of HCT into clinical workflows...
May 23, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/28534525/covalently-linked-dengue-virus-envelope-glycoprotein-dimers-reduce-exposure-of-the-immunodominant-fusion-loop-epitope
#14
Alexander Rouvinski, Wanwisa Dejnirattisai, Pablo Guardado-Calvo, Marie-Christine Vaney, Arvind Sharma, Stéphane Duquerroy, Piyada Supasa, Wiyada Wongwiwat, Ahmed Haouz, Giovanna Barba-Spaeth, Juthathip Mongkolsapaya, Félix A Rey, Gavin R Screaton
A problem in the search for an efficient vaccine against dengue virus is the immunodominance of the fusion loop epitope (FLE), a segment of the envelope protein E that is buried at the interface of the E dimers coating mature viral particles. Anti-FLE antibodies are broadly cross-reactive but poorly neutralizing, displaying a strong infection enhancing potential. FLE exposure takes place via dynamic 'breathing' of E dimers at the virion surface. In contrast, antibodies targeting the E dimer epitope (EDE), readily exposed at the E dimer interface over the region of the conserved fusion loop, are very potent and broadly neutralizing...
May 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28534082/conformational-dynamics-and-alignment-properties-of-loop-lanthanide-binding-tags-lbts-studied-in-interleukin-1%C3%AE
#15
Dominic Barthelmes, Katja Barthelmes, Kai Schnorr, Hendrik R A Jonker, Bianca Bodmer, Karen N Allen, Barbara Imperiali, Harald Schwalbe
Encodable lanthanide binding tags (LBTs) have become an attractive tool in modern structural biology as they can be expressed as fusion proteins of targets of choice. Previously, we have demonstrated the feasibility of inserting encodable LBTs into loop positions of interleukin-1β (Barthelmes et al. in J Am Chem Soc 133:808-819, 2011). Here, we investigate the differences in fast dynamics of selected loop-LBT interleukin-1β constructs by measuring (15)N nuclear spin relaxation experiments. We show that the loop-LBT does not significantly alter the dynamic motions of the host protein in the sub-τc-timescale and that the loop-LBT adopts a rigid conformation with significantly reduced dynamics compared to the terminally attached encodable LBT leading to increased paramagnetic alignment strength...
May 22, 2017: Journal of Biomolecular NMR
https://www.readbyqxmd.com/read/28533135/enhanced-local-disorder-in-a-clinically-elusive-von-willebrand-factor-provokes-high-affinity-platelet-clumping
#16
Alexander Tischer, Venkata R Machha, Juan P Frontroth, Maria A Brehm, Tobias Obser, Reinhard Schneppenheim, Leland Mayne, S Walter Englander, Matthew Auton
Mutation of the cysteines forming the disulfide loop of the platelet GPIbα adhesive A1 domain of von Willebrand factor causes quantitative VWF deficiencies in the blood and von Willebrand disease. We report two cases of transient severe thrombocytopenia induced by DDAVP-treatment. Cys1272Trp and Cys1458Tyr mutations identified by genetic sequencing implicate an abnormal gain-of-function phenotype, evidenced by thrombocytopenia, that quickly relapses back to normal platelet counts and deficient plasma VWF. Using surface plasmon resonance, analytical rheology, and hydrogen-deuterium exchange mass spectrometry (HXMS), we decipher mechanisms of A1-GPIbα mediated platelet adhesion and resolve dynamic secondary structure elements that regulate the binding pathway...
May 19, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28531336/loop-gain-predicts-the-response-to-upper-airway-surgery-in-patients-with-obstructive-sleep-apnoea-ventilatory-control-abnormalities-predict-surgical-responsiveness
#17
Simon A Joosten, Paul Leong, Shane A Landry, Scott A Sands, Philip I Terrill, Dwayne Mann, Anthony Turton, Jhanavi Rangaswamy, Christopher Andara, Glen Burgess, Darren Mansfield, Garun S Hamilton, Bradley A Edwards
Study Objectives: Upper airway surgery is often recommended to treat OSA patients who cannot tolerate continuous positive airways pressure (CPAP). However, the response to surgery is variable, potentially because it does not improve the non-anatomical factors (i.e. loop gain and arousal threshold) causing OSA. Measuring these traits clinically might predict responses to surgery. Our primary objective was to test the value of loop gain and arousal threshold to predict surgical success defined as 50% reduction in apnea-hypopnea index (AHI) and AHI <10 events/hr post-surgery...
May 22, 2017: Sleep
https://www.readbyqxmd.com/read/28529475/fragile-x-associated-tremor-ataxia-syndrome-from-molecular-pathogenesis-to-development-of-therapeutics
#18
REVIEW
Ha Eun Kong, Juan Zhao, Shunliang Xu, Peng Jin, Yan Jin
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a premutation CGG repeat expansion (55-200 repeats) within the 5' UTR of the fragile X gene (FMR1). FXTAS is characterized by intension tremor, cerebellar ataxia, progressive neurodegeneration, parkinsonism and cognitive decline. The development of transgenic mouse and Drosophila melanogaster models carrying an expanded CGG repeat has yielded valuable insight into the pathophysiology of FXTAS. To date, we know of two main molecular mechanisms of this disorder: (1) a toxic gain of function of the expanded CGG-repeat FMR1 mRNA, which results in the binding/sequestration of the CGG-binding proteins; and (2) CGG repeat-associated non-AUG-initiated (RAN) translation, which generates a polyglycine peptide toxic to cells...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28527390/on-filter-direct-amplification-of-legionella-pneumophila-for-rapid-assessment-of-its-abundance-and-viability
#19
Farag A Samhan, Tiffany M Stedtfeld, Hassan Waseem, Maggie R Williams, Robert D Stedtfeld, Syed A Hashsham
Guidelines and regulations to control Legionella pneumophila in cooling water systems of large buildings are evolving due to the increasing number of outbreaks. Rapid, on-site, simple, and sensitive quantification methods that are also able to assess viability may be extremely useful in monitoring and control. Culture-based methods for measuring L. pneumophila may take 4-10 days and qPCR-based methods are also slow, requiring at least a day from sample to result, albeit mainly due to the need for sample transport to a centralized laboratory...
May 13, 2017: Water Research
https://www.readbyqxmd.com/read/28526717/major-contribution-of-the-3-6-7-class-of-trpc-channels-to-myocardial-ischemia-reperfusion-and-cellular-hypoxia-reoxygenation-injuries
#20
Xiju He, Shoutian Li, Benju Liu, Sebastian Susperreguy, Karina Formoso, Jinghong Yao, Jinsong Kang, Anbing Shi, Lutz Birnbaumer, Yanhong Liao
The injury phase after myocardial infarcts occurs during reperfusion and is a consequence of calcium release from internal stores combined with calcium entry, leading to cell death by apoptopic and necrotic processes. The mechanism(s) by which calcium enters cells has(ve) not been identified. Here, we identify canonical transient receptor potential channels (TRPC) 3 and 6 as the cation channels through which most of the damaging calcium enters cells to trigger their death, and we describe mechanisms activated during the injury phase...
May 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
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