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https://www.readbyqxmd.com/read/28720317/dcc-receptors-drive-prefrontal-cortex-maturation-by-determining-dopamine-axon%C3%A2-targeting-in-adolescence
#1
Lauren M Reynolds, Matthew Pokinko, Angélica Torres-Berrío, Santiago Cuesta, Laura C Lambert, Esther Del Cid Pellitero, Michael Wodzinski, Colleen Manitt, Paul Krimpenfort, Bryan Kolb, Cecilia Flores
BACKGROUND: Dopaminergic input to the prefrontal cortex (PFC) increases throughout adolescence and, by establishing precisely localized synapses, calibrates cognitive function. However, why and how mesocortical dopamine axon density increases across adolescence remains unknown. METHODS: We used a developmental application of axon-initiated recombination to label and track the growth of dopamine axons across adolescence in mice. We then paired this recombination with cell-specific knockdown of the netrin-1 receptor DCC to determine its role in adolescent dopamine axon growth...
June 16, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28714144/cerebellins-are-differentially-expressed-in-selective-subsets-of-neurons-throughout-the-brain
#2
Erica Seigneur, Thomas C Südhof
Cerebellins are secreted hexameric proteins that form tripartite complexes with the presynaptic cell-adhesion molecules neurexins or 'deleted-in-colorectal-cancer' (DCC), and the postsynaptic glutamate-receptor-related proteins GluD1 and GluD2. These tripartite complexes are thought to regulate synapses. However, cerebellins are expressed in multiple isoforms whose relative distributions and overall functions are not understood. Three of the four cerebellins, Cbln1, Cbln2, and Cbln4, autonomously assemble into homohexamers, whereas the Cbln3 requires Cbln1 for assembly and secretion...
July 16, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28702704/ezrin-orchestrates-signal-transduction-in-airway-cells
#3
Lei-Miao Yin, Ting-Ting Duan, Luis Ulloa, Yong-Qing Yang
Ezrin is a critical structural protein that organizes receptor complexes and orchestrates their signal transduction. In this study, we review the ezrin-meditated regulation of critical receptor complexes, including the epidermal growth factor receptor (EGFR), CD44, vascular cell adhesion molecule (VCAM), and the deleted in colorectal cancer (DCC) receptor. We also analyze the ezrin-meditated regulation of critical pathways associated with asthma, such as the RhoA, Rho-associated protein kinase (ROCK), and protein kinase A (cAMP/PKA) pathways...
July 13, 2017: Reviews of Physiology, Biochemistry and Pharmacology
https://www.readbyqxmd.com/read/28701345/trim9-dependent-ubiquitination-of-dcc-constrains-kinase-signaling-exocytosis-and-axon-branching
#4
Melissa Plooster, Shalini Menon, Cortney C Winkle, Fabio L Urbina, Caroline Monkiewicz, Kristen D Phend, Richard J Weinberg, Stephanie L Gupton
Extracellular netrin-1 and its receptor DCC promote axon branching in developing cortical neurons. Netrin-dependent morphogenesis is preceded by multimerization of DCC, activation of FAK and Src family kinases, and increases in exocytic vesicle fusion, yet how these occurrences are linked is unknown. Here we demonstrate that TRIM9-dependent ubiquitination of DCC blocks the interaction with and phosphorylation of FAK. Upon netrin-1 stimulation TRIM9 promotes DCC multimerization, but TRIM9-dependent ubiquitination of DCC is reduced, which promotes an interaction with FAK and subsequent FAK activation...
July 12, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28693238/intranuclear-accumulation-of-galectin-3-is-an-independent-prognostic-factor-for-patients-with-distal-cholangiocarcinoma
#5
Tatsuo Shimura, Yasuhide Kofunato, Ryo Okada, Rei Yashima, Yoshihisa Koyama, Kenichiro Araki, Hiroyuki Kuwano, Seiichi Takenoshita
Galectin-3 has been reported to be associated with the prognosis of patients with various malignancies; however, it has not yet been investigated in patients with extrahepatic cholangiocarcinoma (EHCC). Expression of galectin-3 was retrospectively examined in 58 patients with EHCC: 21 with perihilar cholangiocarcinoma and 37 with distal cholangiocarcinoma (DCC). The Cox proportional hazard model was used to identify independent prognostic factors. Intranuclear accumulation of galectin-3 (gal-3-INA) was associated with poorer overall survival (OS) in all patients (P=0...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28691197/loss-of-dcc-in-the-spinal-cord-is-sufficient-to-cause-a-deficit-in-lateralized-motor-control-and-the-switch-to-a-hopping-gait
#6
Jimmy Peng, Julien Ferent, Qingyu Li, Mingwei Liu, Ronan Vinicius da Silva, Hanns Ulrich Zeilhofer, Artur Kania, Ying Zhang, Frédéric Charron
BACKGROUND: Humans with heterozygous mutations in the axon guidance receptor DCC display congenital mirror movements (MMs), which are involuntary movements of body parts, such as fingers, on one side of the body that mirror voluntary movement of the opposite side. In mice, the homozygous Dcc(kanga) mutant allele causes synchronous MM-like hindlimb movements during locomotion, resulting in hopping. In both human and mice, the neuroanatomical defect responsible for the deficit in lateralized motor control remains to be elucidated...
July 10, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28687517/comparing-test-retest-reliability-of-dynamic-functional-connectivity-methods
#7
Ann S Choe, Mary Beth Nebel, Anita D Barber, Jessica R Cohen, Yuting Xu, James J Pekar, Brian Caffo, Martin A Lindquist
Due to the dynamic, condition-dependent nature of brain activity, interest in estimating rapid functional connectivity (FC) changes that occur during resting-state functional magnetic resonance imaging (rs-fMRI) has recently soared. However, studying dynamic FC is methodologically challenging, due to the low signal-to-noise ratio of the blood oxygen level dependent (BOLD) signal in fMRI and the massive number of data points generated during the analysis. Thus, it is important to establish methods and summary measures that maximize reliability and the utility of dynamic FC to provide insight into brain function...
July 5, 2017: NeuroImage
https://www.readbyqxmd.com/read/28679208/spatially-selective-dissection-of-signal-transduction-in-neurons-grown-on-netrin-1-printed-nanoarrays-via-segmented-fluorescence-fluctuation-analysis
#8
Angelica A Gopal, Sebastien G Ricoult, Stephanie N Harris, David Juncker, Timothy E Kennedy, Paul W Wiseman
Axonal growth cones extend during neural development in response to precise distributions of extracellular cues. Deleted in Colorectal Cancer (DCC), a receptor for the chemotropic guidance cue netrin-1, directs F-actin reorganization and is essential for mammalian neural development. To elucidate how the extracellular distribution of netrin-1 influences the distribution of DCC and F-actin within axonal growth cones, we patterned nanoarrays of substrate bound netrin-1 using lift off nanocontact printing. The distribution of DCC and F-actin in embryonic rat cortical neuron growth cones was then imaged using total internal reflection fluorescence (TIRF) microscopy...
July 5, 2017: ACS Nano
https://www.readbyqxmd.com/read/28664225/does-optinab-strategy-stop-and-go-work-in-treatment-of-advanced-pancreatic-cancer-apc-with-nab-paclitaxel-gemcitabine
#9
Valerie Relias, Antonia Maloney, Melissa H Smith, Muhammad Wasif Saif
BACKGROUND: MPACT demonstrated a survival benefit of nab-paclitaxel plus gemcitabine versus gemcitabine in advanced pancreatic cancer (APC). However, sensory peripheral neuropathy is a dose-limiting toxicity and neuromodulators have shown limited, if any activity in ameliorating neuropathy. In colorectal cancer, the OPTIMOX ("stop-and-go") approach offered a strategy to reduce neuropathy. No data exist to support this strategy for nab-paclitaxel in APC. METHODS: Retrospective study of APC patients who developed grade 3 neuropathy during nab-paclitaxel plus gemcitabine was done...
June 29, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28654733/target-directed-dynamic-combinatorial-chemistry-a-study-on-potentials-and-pitfalls-as-exemplified-on-a-bacterial-target
#10
Beat Ernst, Priska Frei, Lijuan Pang, Marleen Silbermann, Deniz Eris, Tobias Mühlethaler, Oliver Schwardt
Target-directed dynamic combinatorial chemistry (DCC) is an emerging technique for the efficient identification of inhibitors of pharmacologically relevant targets. In this contribution, we present an application for a bacterial target, the lectin FimH, a crucial virulence factor of uropathogenic E. coli being the main cause of urinary tract infections. A small dynamic library of acylhydrazones was formed from aldehydes and hydrazides and equilibrated at neutral pH in presence of aniline as nucleophilic catalyst...
June 27, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28645659/synthesis-in-vitro-and-in-vivo-giardicidal-activity-of-nitrothiazole-nsaid-chimeras-displaying-broad-antiprotozoal-spectrum
#11
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...
August 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28621421/roles-of-dscam-in-axonal-decussation-and-fasciculation-of-chick-spinal-interneurons
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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