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https://www.readbyqxmd.com/read/28221346/synthesis-of-ent-be-43547a1-reveals-a-potent-hypoxia-selective-anticancer-agent-and-uncovers-the-biosynthetic-origin-of-the-apd-cld-natural-products
#1
Nikolaj L Villadsen, Kristian M Jacobsen, Ulrik B Keiding, Esben T Weibel, Bjørn Christiansen, Thomas Vosegaard, Morten Bjerring, Frank Jensen, Mogens Johannsen, Thomas Tørring, Thomas B Poulsen
Tumour hypoxia is speculated to be a key driver of therapeutic resistance and metastatic dissemination. Consequently, the discovery of new potent agents that selectively target the hypoxic cell population may reveal new and untapped antitumour mechanisms. Here we demonstrate that the BE-43547 subclass of the APD-CLD (amidopentadienoate-containing cyclolipodepsipeptides) natural products possesses highly hypoxia-selective growth-inhibitory activity against pancreatic cancer cells. To enable this discovery, we have developed the first synthesis of the BE-43547-macrocyclic scaffold in 16 steps (longest linear sequence), which also allowed access to the full panel of relative stereoisomers and ultimately to the assignment of stereochemical configuration...
March 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28219344/origin-and-phylogenetic-status-of-the-local-ashanti-dwarf-pig-adp-of-ghana-based-on-genetic-analysis
#2
Richard Osei-Amponsah, Benjamin M Skinner, Dennis O Adjei, Julien Bauer, Greger Larson, Nabeel A Affara, Carole A Sargent
BACKGROUND: The Ashanti Dwarf Pig (ADP) of Ghana is an endangered pig breed with hardy and disease resistant traits. Characterisation of animal genetic resources provides relevant data for their conservation and sustainable use for food security and economic development. We investigated the origin and phylogenetic status of the local ADP of Ghana and their crosses with modern commercial breeds based on mtDNA, MC1R, Y-chromosome sequence polymorphisms, and genome-wide SNP genotyping. RESULTS: The study involved 164 local pigs sampled from the three agro-ecological zones of Ghana...
February 20, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28216590/initial-results-from-squid-sensor-analysis-and-modeling-for-the-elf-vlf-atmospheric-noise
#3
Huan Hao, Huali Wang, Liang Chen, Jun Wu, Longqing Qiu, Liangliang Rong
In this paper, the amplitude probability density (APD) of the wideband extremely low frequency (ELF) and very low frequency (VLF) atmospheric noise is studied. The electromagnetic signals from the atmosphere, referred to herein as atmospheric noise, was recorded by a mobile low-temperature superconducting quantum interference device (SQUID) receiver under magnetically unshielded conditions. In order to eliminate the adverse effect brought by the geomagnetic activities and powerline, the measured field data was preprocessed to suppress the baseline wandering and harmonics by symmetric wavelet transform and least square methods firstly...
February 14, 2017: Sensors
https://www.readbyqxmd.com/read/28214927/spatiotemporal-differentiation-in-auditory-and-motor-regions-during-auditory-phoneme-discrimination
#4
Annelies Aerts, Gregor Strobbe, Pieter van Mierlo, Robert J Hartsuiker, Paul Corthals, Patrick Santens, Miet De Letter
Auditory phoneme discrimination (APD) is supported by both auditory and motor regions through a sensorimotor interface embedded in a fronto-temporo-parietal cortical network. However, the specific spatiotemporal organization of this network during APD with respect to different types of phonemic contrasts is still unclear. Here, we use source reconstruction, applied to event-related potentials in a group of 47 participants, to uncover a potential spatiotemporal differentiation in these brain regions during a passive and active APD task with respect to place of articulation (PoA), voicing and manner of articulation (MoA)...
February 18, 2017: Acta Neurologica Belgica
https://www.readbyqxmd.com/read/28203415/changes-in-the-action-potential-and-transient-outward-potassium-current-in-cardiomyocytes-during-acute-cardiac-rejection-in-rats
#5
Wenqi Luo, Yixin Jia, Shuai Zheng, Yan Li, Jie Han, Xu Meng
BACKGROUND: Acute cardiac rejection contributes to the changes in the electrophysiological properties of grafted hearts. However, the electrophysiological changes of cardiomyocytes during acute cardiac rejection are still unknown. An understanding of the electrophysiological mechanisms of cardiomyocytes could improve the diagnosis and treatment of acute cardiac rejection. So it is important to characterize the changes in the action potential (AP) and the transient outward potassium current (Ito ) in cardiomyocytes during acute cardiac rejection...
January 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28190860/activated-phosphoinositide-3-kinase-%C3%AE-syndrome-presenting-with-gut-associated-t-cell-lymphoproliferative-disease
#6
Hideto Teranishi, Masataka Ishimura, Yuuki Koga, Katsuhide Eguchi, Motoshi Sonoda, Tetsuko Kobayashi, Satoru Shiraishi, Kentaro Nakashima, Kouji Ikegami, Murasaki Aman, Hidetaka Yamamoto, Hidetoshi Takada, Shouichi Ohga
A 13-year-old boy was admitted to our hospital because of persistent diarrhea, abdominal pain, and bloody stools. The patient had experienced repeated hospitalizations for the treatment of respiratory infections since early childhood. Colonoscopic and pathological studies led to a diagnosis of gut-associated T-cell lymphoproliferative disease (T-cell LPD). Laboratory data showed T-lymphocytopenia (492/µl), increased serum IgG levels (1,984 mg/dl), and low serum antibody titers for specific pathogens. Combined immunodeficiency accompanied by T-LPD suggested the diagnosis of activated PI3Kδ syndrome (APDS)...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28185917/increment-of-late-sodium-currents-in-the-left-atrial-myocytes-and-its-potential-contribution-to-the-increased-susceptibility-of-atrial-fibrillation-in-castrated-male-mice
#7
Yang Zhang, Hui-Min Wang, Ying-Zhe Wang, Yi-Yuan Zhang, Xue-Xin Jin, Yue Zhao, Jin Wang, Yi-Lin Sun, Gen-Long Xue, Peng-Hui Li, Qi-He Huang, Bao-Feng Yang, Zhen-Wei Pan
BACKGROUND: The incidence of atrial fibrillation (AF) is correlated with the declined levels of testosterone in elder men. Late sodium current may exert a role in AF pathogenesis. OBJECTIVE: In this study we explored the effect of testosterone deficiency on AF susceptibility and the therapeutic effect of late sodium current inhibitors in mice. METHODS: Male ICR mice (5-week old) were castrated to establish testosterone deficiency model. One month after castration, dihydrotestosterone (5mg/kg) was administered subcutaneously for 2 months...
February 6, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28182562/in-silico-modeling-of-the-functional-role-of-reduced-sialylation-in-sodium-and-potassium-channel-gating-of-mouse-ventricular-myocytes
#8
Dongping Du, Hui Yang, Andrew R Ednie, Eric S Bennett
Cardiac ion channels are highly glycosylated membrane proteins, with up to 30% of the protein's mass containing glycans. Heart diseases often accompany individuals with congenital disorders of glycosylation (CDG). However, cardiac dysfunction among CDG patients is not yet fully understood. There is an urgent need to study how aberrant glycosylation impacts cardiac electrical signaling. Our previous works reported that congenitally reduced sialylation achieved through deletion of the sialyltransferase gene, ST3Gal4, leads to altered gating of voltage-gated Na+ and K+ channels (Nav and Kv, respectively)...
February 6, 2017: IEEE Journal of Biomedical and Health Informatics
https://www.readbyqxmd.com/read/28179466/blood-based-nfl-a-biomarker-for-differential-diagnosis-of-parkinsonian-disorder
#9
Oskar Hansson, Shorena Janelidze, Sara Hall, Nadia Magdalinou, Andrew J Lees, Ulf Andreasson, Niklas Norgren, Jan Linder, Lars Forsgren, Radu Constantinescu, Henrik Zetterberg, Kaj Blennow
OBJECTIVE: To determine if blood neurofilament light chain (NfL) protein can discriminate between Parkinson disease (PD) and atypical parkinsonian disorders (APD) with equally high diagnostic accuracy as CSF NfL, and can therefore improve the diagnostic workup of parkinsonian disorders. METHODS: The study included 3 independent prospective cohorts: the Lund (n = 278) and London (n = 117) cohorts, comprising healthy controls and patients with PD, progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA), as well as an early disease cohort (n = 109) of patients with PD, PSP, MSA, or CBS with disease duration ≤3 years...
February 8, 2017: Neurology
https://www.readbyqxmd.com/read/28177123/katp-channel-inhibition-blunts-electromechanical-decline-during-hypoxia-in-left-ventricular-working-rabbit-hearts
#10
Kara Garrott, Sarah Kuzmiak-Glancy, Anastasia Wengrowski, Hanyu Zhang, Jack Rogers, Matthew Kay
Sarcolemmal KATP channel activation in isolated cells is generally understood, yet the relationship between myocardial oxygenation and KATP activation in excised working rabbit hearts remains unknown. We optically mapped action potentials (APs) in excised rabbit hearts to test the hypothesis that hypoxic changes would be more severe in LV working hearts (LWHs) than Langendorff (LANG) perfused hearts. We further hypothesized that KATP inhibition would prevent those changes. Optical APs were mapped while measuring LV developed pressure (LVDP), coronary flow rate (CFR), and oxygen consumption (MVO2 ) in LANG and LWHs...
February 8, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28167755/conformational-disruption-of-pi3k%C3%AE-regulation-by-immunodeficiency-mutations-in-pik3cd-and-pik3r1
#11
Gillian L Dornan, Braden D Siempelkamp, Meredith L Jenkins, Oscar Vadas, Carrie L Lucas, John E Burke
Activated PI3K Delta Syndrome (APDS) is a primary immunodeficiency disease caused by activating mutations in either the leukocyte-restricted p110δ catalytic (PIK3CD) subunit or the ubiquitously expressed p85α regulatory (PIK3R1) subunit of class IA phosphoinositide 3-kinases (PI3Ks). There are two classes of APDS: APDS1 that arises from p110δ mutations that are analogous to oncogenic mutations found in the broadly expressed p110α subunit and APDS2 that occurs from a splice mutation resulting in p85α with a central deletion (Δ434-475)...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28160219/automatic-segmentation-of-left-ventricle-cavity-from-short-axis-cardiac-magnetic-resonance-images
#12
Xulei Yang, Qing Song, Yi Su
In this paper, a computational framework is proposed to perform a fully automatic segmentation of the left ventricle (LV) cavity from short-axis cardiac magnetic resonance (CMR) images. In the initial phase, the region of interest (ROI) is automatically identified on the first image frame of the CMR slices. This is done by partitioning the image into different regions using a standard fuzzy c-means (FCM) clustering algorithm where the LV region is identified according to its intensity, size and circularity in the image...
February 3, 2017: Medical & Biological Engineering & Computing
https://www.readbyqxmd.com/read/28158968/a-genome-wide-association-study-in-a-large-f2-cross-of-laying-hens-reveals-novel-genomic-regions-associated-with-feather-pecking-and-aggressive-pecking-behavior
#13
Vanessa Lutz, Patrick Stratz, Siegfried Preuß, Jens Tetens, Michael A Grashorn, Werner Bessei, Jörn Bennewitz
BACKGROUND: Feather pecking and aggressive pecking in laying hens are serious economic and welfare issues. In spite of extensive research on feather pecking during the last decades, the motivation for this behavior is still not clear. A small to moderate heritability has frequently been reported for these traits. Recently, we identified several single-nucleotide polymorphisms (SNPs) associated with feather pecking by mapping selection signatures in two divergent feather pecking lines...
February 3, 2017: Genetics, Selection, Evolution: GSE
https://www.readbyqxmd.com/read/28157419/chemical-interaction-analysis-of-an-adhesive-containing-10-methacryloyloxydecyl-dihydrogen-phosphate-10-mdp-with-the-dentin-in-noncarious-cervical-lesions
#14
Bmb Oliveira, Alm Ulbaldini, F Sato, M L Baesso, A C Bento, Lhc Andrade, S M Lima, R C Pascotto
The purpose of this study was to evaluate the chemical bonds of a self-etch 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) adhesive to natural noncarious cervical lesions (NCCLs) and compare them with those occurring in sclerotic dentin in artificially prepared defects (APDs). Four human teeth with natural NCCLs on the buccal surface were selected. Artificial defects matching the natural lesions were prepared on the lingual surface of the same teeth serving as control. Micro-Raman (MR) spectroscopy was used to quantify mineral content in natural NCCLs and in APDs...
February 3, 2017: Operative Dentistry
https://www.readbyqxmd.com/read/28156609/icu-deaths-in-patients-with-advanced-cancer-criteria-to-decrease-potentially-inappropriate-admissions-and-analysis-of-advance-planning-discussions
#15
Alva B Weir
: 47 Background: A significant number of advanced cancer admissions to intensive care unit (ICU) are inappropriate, as they do not prolonged survival. No clear consensus criteria for reasonable admissions of advanced cancer patients have been developed. METHODS: We established four criteria for ICU admissions in advanced cancer patients: post procedure complication, recent cancer diagnosis, good performance status and life expectancy of > 6 months. We reviewed charts of all patients who died in the ICU at a university-affiliated hospital between 2005-2010...
October 9, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28127739/phosphate-equilibration-rate-and-daily-clearance-in-patients-on-capd-ccpd-and-apd
#16
Rafael Gomez, Jacek Waniewski, Adelaida Zapata, Mauro Pietribiasi, Bengt Lindholm
BACKGROUND: Criteria for how to assess removal rate of inorganic phosphorous (iP) in peritoneal dialysis (PD) and whether iP removal differs between different PD modalities are debated. METHODS: In a cross-sectional study, 73 prevalent patients on continuous ambulatory PD (n = 16), continuous cyclic PD (n = 8) or automated PD (n = 49) with mean age 54 (range, 18-87) years, 46 males, underwent standard peritoneal equilibration test (PET) and 24-hour collection of dialysate with measurements of iP, urea and creatinine in all samples and bags...
January 24, 2017: International Journal of Artificial Organs
https://www.readbyqxmd.com/read/28113987/optical-characterization-of-tissue-phantoms-using-a-silicon-integrated-fdnirs-system-on-chip
#17
Chirag C Sthalekar, Yun Miao, Valencia Joyner Koomson
An interface circuit with signal processing and digitizing circuits for a high frequency, large area avalanche photodiode (APD) has been integrated in a 130 nm BiCMOS chip. The system enables the absolute oximetry of tissue using frequency domain Near Infrared Spectroscopy (fdNIRS). The system measures the light absorbed and scattered by the tissue by measuring the reduction in the amplitude of signal and phase shift introduced between the light source and detector which are placed a finite distance away from each other...
September 22, 2016: IEEE Transactions on Biomedical Circuits and Systems
https://www.readbyqxmd.com/read/28111223/parenchyma-to-hydronephrosis-area-ratio-phar-is-a-promising-outcome-measure-to-quantify-upper-tract-changes-in-infants-with-high-grade-prenatal-hydronephrosis
#18
Mandy Rickard, Armando J Lorenzo, Caroline Munoz, Luis H Braga
OBJECTIVE: To explore the value of renal parenchyma-to-hydronephrosis area ratio (PHAR) in detecting trends of hydronephrosis (HN) improvement or worsening and response to surgical intervention. MATERIALS AND METHODS: Initial and follow-up sagittal renal ultrasound images of patients entered into a prenatal HN database from 2008-2016, with baseline SFU grades III and IV HN and without vesicoureteral reflux, were evaluated using NIH-sponsored image-processing software...
January 19, 2017: Urology
https://www.readbyqxmd.com/read/28104464/genetic-defects-in-pi3k%C3%AE-affect-b-cell-differentiation-and-maturation-leading-to-hypogammaglobulineamia-and-recurrent-infections
#19
Marjolein Wentink, Virgil Dalm, Arjan C Lankester, Pauline A van Schouwenburg, Liesbeth Schölvinck, Tomas Kalina, Radana Zachova, Anna Sediva, Annechien Lambeck, Ingrid Pico-Knijnenburg, Jacques J M van Dongen, Malgorzata Pac, Ewa Bernatowska, Martin van Hagen, Gertjan Driessen, Mirjam van der Burg
BACKGROUND: Mutations in PIK3CD and PIK3R1 cause activated PI3K-δ syndrome (APDS) by dysregulation of the PI3K-AKT pathway. METHODS: We studied precursor and peripheral B-cell differentiation and apoptosis via flowcytometry. Furthermore, we performed AKT-phosphorylation assays and somatic hypermutations (SHM) and class switch recombination (CSR) analysis. RESULTS: We identified 13 patients of whom 3 had new mutations in PIK3CD or PIK3R1. Patients had low total B-cell numbers with increased frequencies of transitional B cells and plasmablasts, while the precursor B-cell compartment in bone marrow was relatively normal...
January 17, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28103138/discovery-of-a-novel-splice-variant-of-fcar-cd89-unravels-sequence-segments-necessary-for-efficient-secretion-a-story-of-bad-signal-peptides-and-good-ones-that-nevertheless-do-not-make-it
#20
Wai-Heng Lua, Wei-Li Ling, Chinh Tran-To Su, Joshua Yi Yeo, Chandra Shekhar Verma, Birgit Eisenhaber, Frank Eisenhaber, Samuel Ken-En Gan
The IgA receptor, Fcar (CD89) consists of five sequence segments: two segments (S1, S2) forming the potential signal peptide, two extracellular EC domains that include the IgA binding site, and the transmembrane and cytoplasmic tail (TM/C) region. Numerous Fcar splice variants have been reported with various combinations of the sequence segments mentioned above. Here, we report a novel splice variant termed variant APD isolated from a healthy volunteer that lacks only the IgA-binding EC1 domain. Despite possessing the complete signal peptide S1+S2, the variant APD is only found in the intracellular space whereas the wild-type variant 1 is efficiently secreted and variant 4 leaks to the extracellular space...
January 19, 2017: Cell Cycle
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