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https://www.readbyqxmd.com/read/28645659/synthesis-in-vitro-and-in-vivo-giardicidal-activity-of-nitrothiazole-nsaid-chimeras-displaying-broad-antiprotozoal-spectrum
#1
Blanca Colín-Lozano, Ismael León-Rivera, Manuel Jesús Chan-Bacab, Benjamín Otto Ortega-Morales, Rosa Moo-Puc, Vanessa López-Guerrero, Emanuel Hernández-Núñez, Raúl Argüello-Garcia, Thomas Scior, Elizabeth Barbosa-Cabrera, Gabriel Navarrete-Vázquez
We designed and synthesized five new 5-nitrothiazole-NSAID chimeras as analogues of nitazoxanide, using a DCC-activated amidation. Compounds 1-5 were tested in vitro against a panel of five protozoa: 2 amitochondriates (Giardia intestinalis, Trichomonas vaginalis) and 3 kinetoplastids (Leishmania mexicana, Leishmania amazonensis and Trypanosoma cruzi). All chimeras showed broad spectrum and potent antiprotozoal activities, with IC50 values ranging from the low micromolar to nanomolar order. Compounds 1-5 were even more active than metronidazole and nitazoxanide, two marketed first-line drugs against giardiasis...
May 24, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28621421/roles-of-dscam-in-axonal-decussation-and-fasciculation-of-chick-spinal-interneurons
#2
Oksana Cohen, Lilach Vald, Masahito Yamagata, Joshua R Sanes, Avihu Klar
The ventral midline of the embryonic neural tube, the floor plate, has a profound role in guiding axons during embryonic development. Floor plate-derived guidance cues attract or repel axons, depending on the neuronal subtype and developmental stage. Netrin-1 and its receptor, Deleted in Colon Carcinoma (DCC), are the key constituents of commissurral axons guidance cues toward the floor plate. Recent studies have implicated Down Syndrome Cell Adhesion Molecule (Dscam) as an additional Netrin-1 receptor. In this study, we examined the role of Dscam in guiding defined spinal dorsal interneuron populations...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28597937/frustration-guided-motion-planning-reveals-conformational-transitions-in-proteins
#3
Dominik Budday, Rasmus Fonseca, Sigrid Leyendecker, Henry van den Bedem
Proteins exist as conformational ensembles, exchanging between substates to perform their function. Advances in experimental techniques yield unprecedented access to structural snapshots of their conformational landscape. However, computationally modeling how proteins use collective motions to transition between substates is challenging owing to a rugged landscape and large energy barriers. Here, we present a new, robotics-inspired motion planning procedure called dCC-RRT that navigates the rugged landscape between substates by introducing dynamic, interatomic constraints to modulate frustration...
June 9, 2017: Proteins
https://www.readbyqxmd.com/read/28588032/inactivation-of-%C3%AE-secretases-leads-to-accumulation-of-substrates-and-non-alzheimer-neurodegeneration
#4
Hermien Acx, Lutgarde Serneels, Enrico Radaelli, Serge Muyldermans, Cécile Vincke, Elise Pepermans, Ulrike Müller, Lucía Chávez-Gutiérrez, Bart De Strooper
γ-Secretases are a family of intramembrane cleaving aspartyl proteases and important drug targets in Alzheimer's disease. Here, we generated mice deficient for all γ-secretases in the pyramidal neurons of the postnatal forebrain by deleting the three anterior pharynx defective 1 (Aph1) subunits (Aph1abc cKO Cre(+)). The mice show progressive cortical atrophy, neuronal loss, and gliosis. Interestingly, this is associated with more than 10-fold accumulation of membrane-bound fragments of App, Aplp1, Nrg1, and Dcc, while other known substrates of γ-secretase such as Aplp2, Lrp1, and Sdc3 accumulate to lesser extents...
June 6, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28578361/current-umbilical-cord-clamping-practices-and-attitudes-of-obstetricians-and-midwives-toward-delayed-cord-clamping-in-saudi-arabia
#5
Nadia O Ibrahim, Hatouf H Sukkarieh, Rami T Bustami, Elaf A Alshammari, Lama Y Alasmari, Hanan M Al-Kadri
BACKGROUND: In Saudi Arabia, as in many countries, there is usually no clear definition of the timing of umbilical cord clamping (UCC) in the policies and procedures used by hospitals. The World Health Organization (WHO) recommends delayed cord clamping (DCC) ( > 1 minute after birth) as it can significantly improve hemodynamics and long-term neurodevelopment. OBJECTIVE: To investigate current practices of healthcare professionals on the timing of UCC in Saudi Arabia...
May 2017: Annals of Saudi Medicine
https://www.readbyqxmd.com/read/28576474/netrins-as-prophylactic-targets-in-skeletal-diseases-a-double-edged-sword
#6
REVIEW
Kenta Maruyama, Naoki Takemura, Mikaël M Martino, Takeshi Kondo, Shizuo Akira
The netrin family of proteins are involved in axon guidance during central nervous system development. In vertebrates, two membrane bound forms and five secreted forms of netrin have been reported. In addition to their critical role in neural morphogenesis, a growing number of reports suggest that netrin family proteins also play a role in inflammatory conditions, angiogenesis, and tumorigenesis. In these processes, Unc5 and DCC family proteins serve as receptors of netrin proteins. Recently, it was reported that some netrin family proteins may be involved in the pathogenesis of skeletal diseases including osteoporosis and arthritis...
May 30, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28571327/the-covalent-interaction-between-dihydrogen-and-gold-a-rotational-spectroscopic-study-of-h2-aucl
#7
Daniel A Obenchain, Derek S Frank, G S Grubbs, Herbert M Pickett, Stewart E Novick
The pure rotational transitions of H2-AuCl have been measured using a pulsed-jet cavity Fourier transform microwave spectrometer equipped with a laser ablation source. The structure was found to be T-shaped, with the H-H bond interacting with the gold atom. Both (35)Cl and (37)Cl isotopologues have been measured for both ortho and para states of H2. Rotational constants, quartic centrifugal distortion constants, and nuclear quadrupole coupling constants for gold and chlorine have been determined. The use of the nuclear spin-nuclear spin interaction terms Daa, Dbb, and Dcc for H2 were required to fit the ortho state of hydrogen, as well as a nuclear-spin rotation constant Caa...
May 28, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28562241/cooperation-between-a-hierarchical-set-of-recruitment-sites-targets-the-x-chromosome-for-dosage-compensation
#8
Sarah Elizabeth Albritton, Anna-Lena Kranz, Lara Heermans Winterkorn, Lena Annika Street, Sevinc Ercan
In many organisms, it remains unclear how X chromosomes are specified for dosage compensation, since DNA sequence motifs shown to be important for dosage compensation complex (DCC) recruitment are themselves not X-specific. Here, we addressed this problem in C. elegans. We found that the DCC recruiter, SDC-2, is required to maintain open chromatin at a small number of primary DCC recruitment sites, whose sequence and genomic context are X-specific. Along the X, primary recruitment sites are interspersed with secondary sites, whose function is X-dependent...
May 30, 2017: ELife
https://www.readbyqxmd.com/read/28547864/sociodemographic-determinants-of-spatial-disparities-in-early-childhood-caries-an-ecological-analysis-in-braunschweig-germany
#9
Frederic Meyer, André Karch, Kristin Maria Schlinkmann, Johannes Dreesman, Johannes Horn, Nicole Rübsamen, Henny Sudradjat, Rainer Schubert, Rafael Mikolajczyk
OBJECTIVES: To identify spatial disparities in dental caries experience (measured by dmft (decayed missing filled teeth) index) of children in the city of Braunschweig and to evaluate whether these disparities can be explained by sociodemographic characteristics. METHODS: We examined the dental health of children aged 3-6 years visiting a daycare centre (DCC) in the metropolitan area of Braunschweig between 2009 and 2014 by combining data on dental health from the annual visits of the local health service with aggregated data on sociodemographic factors for Braunschweig's city districts...
May 26, 2017: Community Dentistry and Oral Epidemiology
https://www.readbyqxmd.com/read/28546529/the-safety-of-electrical-cardioversion-under-the-control-of-transesophageal-echocardiography-in-patients-with-atrial-fibrillation-and-inadequate-anticoagulation
#10
Joanna Zaprutko, Artur Baszko, Michał Michalak, Karol Kochman, Radosław Szymański, Jan Kłopocki, Anna Nowicka, Rafał Dankowski, Marek Michalski, Piotr Kałmucki, Andrzej Szyszka
INTRODUCTION    Restoring sinus rhythm in patients with atrial fibrillation (AF)/atrial flutter (AF) requires adequate oral anticoagulation (OAC) prior to direct current cardioversion (DCC). Some patients eligible for DCC are not properly anticoagulated. OBJECTIVES    Assessment of risk factors for thrombus and spontaneous echo contrast (SEC) in the left atrium (LA) as well as the safety profile of DCC under transesophageal echocardiography control (TEE) in patients with inadequate anticoagulation. PATIENTS AND METHODS    From the cohort of 316 patients admitted for DCC, 139 (age 63...
May 25, 2017: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/28538099/iodide-selective-synthetic-ion-channels-based-on-shape-persistent-organic-cages
#11
Bahiru Punja Benke, Pulakesh Aich, Younghoon Kim, Kyung Lock Kim, Md Rumum Rohman, Soonsang Hong, In-Chul Hwang, Eun Hui Lee, Joon Ho Roh, Kimoon Kim
We report here a synthetic ion channel developed from a shape-persistent porphyrin-based covalent organic cage. The cage was synthesized by employing a synthetically economical dynamic covalent chemistry (DCC) approach. The organic cage selectively transports biologically relevant iodide ions over other inorganic anions by a dehydration-driven, channel mechanism as evidenced by vesicle-based fluorescence assays and planar lipid bilayer-based single channel recordings. Furthermore, the organic cage appears to facilitate iodide transport across the membrane of a living cell, suggesting that the cage could be useful as a biological tool that may replace defective iodide channels in living systems...
June 7, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28537853/dermatology-discharge-continuity-clinic-enhances-resident-autonomy-and-insight-into-transitions-of-care-competencies-a-cross-sectional-survey-study
#12
Jasmine Rana, Arash Mostaghimi
Dermatology residents perform consults on hospitalized patients, but are often limited in their ability to follow-up with these patients after discharge, leading to inadequate follow-up and understanding of post-discharge transitions of care. In 2013, a discharge continuity clinic (DCC) staffed by the inpatient consult dermatology resident and attending dermatologist was established at one of the four adult hospital sites residents rotate through in the Harvard Combined Dermatology Residency Program. Resident perceptions about the DCC and their educational experience on inpatient consult rotations with a DCC and without a DCC were obtained using a cross-sectional survey instrument in June 2016...
May 15, 2017: Dermatology Online Journal
https://www.readbyqxmd.com/read/28510597/ubiquitylation-of-the-acetyltransferase-mof-in-drosophila-melanogaster
#13
Sarah Schunter, Raffaella Villa, Victoria Flynn, Jan B Heidelberger, Anne-Kathrin Classen, Petra Beli, Peter B Becker
The nuclear acetyltransferase MOF (KAT8 in mammals) is a subunit of at least two multi-component complexes involved in transcription regulation. In the context of complexes of the 'Non-Specific-Lethal' (NSL) type it controls transcription initiation of many nuclear housekeeping genes and of mitochondrial genes. While this function is conserved in metazoans, MOF has an additional, specific function in Drosophila in the context of dosage compensation. As a subunit of the male-specific-lethal dosage compensation complex (MSL-DCC) it contributes to the doubling of transcription output from the single male X chromosome by acetylating histone H4...
2017: PloS One
https://www.readbyqxmd.com/read/28507510/enhanced-axonal-extension-of-subcortical-projection-neurons-isolated-from-murine-embryonic-cortex-using-neuropilin-1
#14
Noritaka Sano, Takafumi Shimogawa, Hideya Sakaguchi, Yoshihiko Ioroi, Yoshifumi Miyawaki, Asuka Morizane, Susumu Miyamoto, Jun Takahashi
The cerebral cortical tissue of murine embryo and pluripotent stem cell (PSC)-derived neurons can survive in the brain and extend axons to the spinal cord. For efficient cell integration to the corticospinal tract (CST) after transplantation, the induction or selection of cortical motor neurons is important. However, precise information about the appropriate cell population remains unclear. To address this issue, we isolated cells expressing Neuropilin-1 (NRP1), a major axon guidance molecule receptor during the early developmental stage, from E14...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28501100/comparison-of-direct-current-synchronized-cardioversion-to-ibutilide-guided-catheter-ablation-for-long-term-sinus-rhythm-maintenance-after-isolated-pulmonary-vein-isolation-of-persistent-atrial-fibrillation
#15
Maojing Wang, Qing Zhao, Wei Ding, Shanglang Cai
Use of the antiarrhythmic ibutilide after isolated pulmonary vein isolation (PVI) might distinguish atrial remodeling severity and cases requiring further substrate modification, thereby improving efficacy of persistent atrial fibrillation (AF) treatment. Ninety-six consecutive patients with persistent AF were randomized after PVI to either direct current synchronized cardioversion (DCC group, n = 48) or 1 mg of intravenous ibutilide (ibutilide group, n = 48) followed by no further intervention if AF converted to sinus rhythm (SR) within 30 minutes (ibutilide conversion subgroup) or by complex fractionated atrial electrogram (CFAE) ablation until SR recovery or complete CFAE elimination (ibutilide nonconversion subgroup)...
March 29, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28500655/discovery-and-validation-of-candidate-host-dna-methylation-markers-for-detection-of-cervical-precancer-and-cancer
#16
Megan A Clarke, Patricia Luhn, Julia C Gage, Clara Bodelon, S Terence Dunn, Joan Walker, Rosemary Zuna, Stephen Hewitt, J Keith Killian, Liying Yan, Andrew Miller, Mark Schiffman, Nicolas Wentzensen
Human papillomavirus (HPV) testing has been recently introduced as an alternative to cytology for cervical cancer screening. However, since most HPV infections clear without causing clinically relevant lesions, additional triage tests are required to identify women who are at high risk of developing cancer. We performed DNA methylation profiling on formalin-fixed, paraffin-embedded tissue specimens from women with benign HPV16 infection and histologically confirmed cervical intraepithelial neoplasia grade 3, and cancer using a bead-based microarray covering 1,500 CpG sites in over 800 genes...
May 13, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28499202/novel-dual-ves-phospholipid-self-assembled-liposomes-with-an-extremely-high-drug-loading-efficiency
#17
Yongpeng Hou, Chen Yao, Longbing Ling, Yawei Du, Ruiyu He, Muhammad Ismail, Ying Zhang, Zhenglin Fu, Xinsong Li
Vitamin E succinate (VES), a unique selective anti-cancer drug, has attracted much attention for its ability to induce apoptosis in various cancer cells. Importantly, it has been reported that VES is largely non-toxic to normal cells. However, poor aqueous solubility and bioavailability extensively restricted its clinical utility. In this report, dual VES phospholipid conjugate (di-VES-GPC) prodrug based liposomes were prepared in order to develop an efficient delivery system for VES. Di-VES-GPC was first synthesized by conjugating VES with l-α-glycerophosphorylcholine (GPC) using N,N'-dicyclohexylcarbodiimide (DCC) as a coupling agent...
May 2, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28483977/uncoupling-of-unc5c-with-polymerized-tubb3-in-microtubules-mediates-netrin-1-repulsion
#18
Qiangqiang Shao, Tao Yang, Huai Huang, Farrah Alarmanazi, Guofa Liu
Modulation of microtubule (MT) dynamics is a key event of cytoskeleton remodeling in the growth cone (GC) during axon outgrowth and pathfinding. Our previous studies have shown that the direct interaction of netrin receptor DCC and DSCAM with polymerized TUBB3, a neuron-specific MT subunit in the brain, is required for netrin-1-mediated axon outgrowth, branching, and attraction. Here, we show that uncoupling of polymerized TUBB3 with netrin-1-repulsive receptor UNC5C is involved in netrin-1-mediated axonal repulsion...
June 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28479354/lyophilization-cycle-design-for-dual-chamber-cartridges-and-a-method-for-online-process-control-the-dcc-lyomate-procedure
#19
Christoph Korpus, Wolfgang Friess
Freeze-drying process design is a challenging task that necessitates a profound understanding of the complex interrelation among critical process parameters (e.g., shelf temperature and chamber pressure), heat transfer characteristics of the involved materials (e.g., product containers and holder devices), and critical quality attributes of the product (e.g., collapse temperatures). The Dual Chamber Cartridge "(DCC) LyoMate" (from lyophilization and automated) is a manometric temperature measurement-based process control strategy that was developed within this study to streamline this complicated task...
May 4, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28460312/cinnamoylated-chloroquine-analogues-a-new-structural-class-of-antimalarial-agents
#20
Venkatareddy Gayam, Subban Ravi
A novel series of cinnamoylated chloroquine hybrid analogues were synthesized and evaluated as antimalarial agents. The trans cinnamic acid derivatives (3-8) were synthesized by utilizing substituted aldehydes and malanoic acid in DMF catalysed by DABCO. The final cinnamoylated chloroquine analogues (9-14) were synthesized by utilizing DCC coupling reagent. The amido chloroquine (17) was prepared from acid (16) and compound 2 in benzene using SOCl2 as chlorinating agent. The corresponding ester (15) was prepared from 2-hydroxy acetophenone and 2-bromoacetates in actonitrile in presence of K2CO3 as base followed by basic hydrolysis...
April 25, 2017: European Journal of Medicinal Chemistry
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