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https://www.readbyqxmd.com/read/29227174/gambogic-amide-a-selective-trka-agonist-does-not-improve-outcomes-from-traumatic-brain-injury-in-mice
#1
Maddison R Johnstone, Mujun Sun, Caroline J Taylor, Rhys D Brady, Brian L Grills, Jarrod E Church, Sandy R Shultz, Stuart J McDonald
OBJECTIVES: There is evidence that treatment with nerve growth factor (NGF) may reduce neuroinflammation and apoptosis after a traumatic brain injury (TBI). NGF is thought to exert its effects via binding to either TrkA or p75 neurotrophin receptors. This study aimed to investigate the effects of a selective TrkA agonist, gambogic amide (GA), on TBI pathology and outcomes in mice following lateral fluid percussion injury. METHODS: Male C57BL/6 mice were given either a TBI or sham injury, and then received subcutaneous injections of either 2 mg/kg of GA or vehicle at 1, 24, and 48 h post-injury...
December 11, 2017: Brain Injury: [BI]
https://www.readbyqxmd.com/read/29222769/neurotrophic-factors-an-overview
#2
Stephen D Skaper
The neurotrophins are a family of closely related proteins that were first identified as survival factors for sympathetic and sensory neurons and have since been shown to control a number of aspects of survival, development, and function of neurons in both the central and peripheral nervous systems. Limiting quantities of neurotrophins during development control the numbers of surviving neurons to ensure a match between neurons and the requirement for a suitable density of target innervation. Biological effects of each of the four mammalian neurotrophins are mediated through activation of one or more of the three members of the tropomyosin-related kinase (Trk) family of receptor tyrosine kinases (TrkA, TrkB, and TrkC)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29213058/interplay-between-global-and-pathway-specific-synaptic-plasticity-in-ca1-pyramidal-cells
#3
Sven Berberich, Jörg Pohle, Marie Pollard, Janet Barroso-Flores, Georg Köhr
Mechanisms underlying information storage have been depicted for global cell-wide and pathway-specific synaptic plasticity. Yet, little is known how these forms of plasticity interact to enhance synaptic competition and network stability. We examined synaptic interactions between apical and basal dendrites of CA1 pyramidal neurons in mouse hippocampal slices. Bursts (50 Hz) of three action potentials (AP-bursts) paired with preceding presynaptic stimulation in stratum radiatum specifically led to LTP of the paired pathway in adult mice (P75)...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29202822/the-p75ntr-mediated-effect-of-nerve-growth-factor-in-l6c5-myogenic-cells
#4
Alessandra de Perini, Ivan Dimauro, Guglielmo Duranti, Cristina Fantini, Neri Mercatelli, Roberta Ceci, Luigi Di Luigi, Stefania Sabatini, Daniela Caporossi
OBJECTIVE: During muscle development or regeneration, myocytes produce nerve growth factor (NGF) as well as its tyrosine-kinase and p75-neurotrophin (p75NTR) receptors. It has been published that the p75NTR receptor could represent a key regulator of NGF-mediated myoprotective effect on satellite cells, but the precise function of NGF/p75 signaling pathway on myogenic cell proliferation, survival and differentiation remains fragmented and controversial. Here, we verified the role of NGF in the growth, survival and differentiation of p75NTR-expressing L6C5 myogenic cells, specifically inquiring for the putative involvement of the nuclear factor κB (NFκB) and the small heat shock proteins (sHSPs) αB-crystallin and Hsp27 in these processes...
December 4, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/29190781/roles-of-cd34-cells-and-alk5-signaling-in-the-reconstruction-of-seminiferous-tubule-like-structures-in-3-d-re-aggregate-culture-of-dissociated-cells-from-neonatal-mouse-testes
#5
Shin-Ichi Abe, Kazuko Abe, Jidong Zhang, Tomoaki Harada, Go Mizumoto, Hiroki Oshikawa, Haruhiko Akiyama, Kenji Shimamura
Tissue reconstruction in vitro can provide, if successful, a refined and simple system to analyze the underlying mechanisms that drive the morphogenesis and maintain the ordered structure. We have recently succeeded in reconstruction of seminiferous cord-like and tubule-like structures using 3-D re-aggregate culture of dissociated testicular cells. In testis formation, endothelial cells that migrated from mesonephroi to embryonic gonads have been shown to be critical for development of testis cords, but how endothelial cells contribute to testis cord formation remains unknown...
2017: PloS One
https://www.readbyqxmd.com/read/29183255/suckling-in-litters-with-different-sizes-and-early-and-late-swimming-exercise-differentially-modulates-anxiety-like-behavior-memory-and-electrocorticogram-potentiation-after-spreading-depression-in-rats
#6
Mariana Barros E Silva-Gondim, Thays Kallyne Marinho de Souza, Marcelo Cairrão Araújo Rodrigues, Rubem Carlos Araújo Guedes
OBJECTIVE: Analyze the hypothesis that swimming exercise, in rats suckled under distinct litter sizes, alters behavioral parameters suggestive of anxiety and recognition memory, and the electrocorticogram potentiation that occurs after the excitability-related phenomenon that is known as cortical spreading depression (CSD). METHODS: Male Wistar rats were suckled in litters with six or 12 pups (L6 and L12 groups). Animals swam at postnatal days (P) 8-23, or P60-P75 (early-exercised or late-exercised groups, respectively), or remained no-exercised...
November 28, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/29182970/time-to-continuous-electroencephalogram-in-repeated-admissions-to-the-pediatric-intensive-care-unit
#7
Iván Sánchez Fernández, Arnold J Sansevere, Marina Gaínza-Lein, Ersida Buraniqi, Robert C Tasker, Tobias Loddenkemper
PURPOSE: Describe timing from intensive care unit (ICU) admission to initiation of continuous electroencephalogram (cEEG) in repeated ICU admissions. METHOD: We performed a retrospective observational study in pediatric patients who underwent repeated ICU admissions with cEEG from 2011 to 2013. The main outcome measure was time from ICU admission to cEEG. RESULTS: There were 41 patients (54% males) with at least 2 ICU admissions with cEEG (median (p25-p75) age at first admission: 3...
November 21, 2017: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/29178434/demonstration-of-an-anti-hyperalgesic-effect-of-a-novel-pan-trk-inhibitor-pf-06273340-in-a-battery-of-human-evoked-pain-models
#8
Peter Loudon, Pieter Siebenga, Donal Gorman, Katrina Gore, Pinky Dua, Guido van Amerongen, Justin L Hay, Geert Jan Groeneveld, Richard P Butt
AIM(S): Inhibitors of nerve growth factor (NGF) reduce pain in several chronic pain indications. NGF signals through tyrosine kinase receptors of the tropomyosin-related kinase (Trk) family and the unrelated p75 receptor. PF-06273340 is a small molecule inhibitor of Trks A, B and C that reduces pain in nonclinical models and this study aimed to investigate the pharmacodynamics of this first in class molecule in humans. METHODS: A randomized, double blind, single dose, placebo and active-controlled 5 period cross-over study was conducted in healthy human subjects (NCT02260947)...
November 27, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29175861/ngf-reprograms-metastatic-melanoma-to-a-bipotent-glial-melanocyte-neural-crest-like-precursor
#9
Jennifer C Kasemeier-Kulesa, Morgan H Romine, Jason A Morrison, Caleb M Bailey, Danny R Welch, Paul M Kulesa
Melanoma pathogenesis from normal neural crest-derived melanocytes is often fatal due to aggressive cell invasion throughout the body. The identification of signals that reprogram de-differentiated, metastatic melanoma cells to a less aggressive and stable phenotype would provide a novel strategy to limit disease progression. In this study, we identify and test the function of developmental signals within the chick embryonic neural crest microenvironment to reprogram and sustain the transition of human metastatic melanoma to a neural crest cell-like phenotype...
November 24, 2017: Biology Open
https://www.readbyqxmd.com/read/29169704/cumulative-incidence-and-predictive-factors-of-radiation-cystitis-in-patients-with-localized-prostate-cancer
#10
D Afonso-João, L Pacheco-Figueiredo, T Antunes-Lopes, L A Morgado, V Azevedo, L Vendeira, J Silva, C Martins-Silva
PURPOSE: To determine the cumulative incidence of overall and severe radiation cystitis in a high volume cohort of patients and to investigate its potential predictive factors. METHODS: We have performed a retrospective analysis of clinical data from patients diagnosed with localized prostate cancer and treated with radiotherapy at our institution (June 2005-January 2013), and quantified the cumulative incidence of radiation cystitis. Cox regression analysis and Kaplan-Meier curves were computed to evaluate the determinants of radiation cystitis...
November 20, 2017: Actas Urologicas Españolas
https://www.readbyqxmd.com/read/29168169/response-to-clobazam-in-continuous-spike-wave-during-sleep
#11
Clemente Vega, Ivan Sánchez Fernández, Jurriaan Peters, Maria S Thome-Souza, Michele Jackson, Masanori Takeoka, Greta N Wilkening, Phillip L Pearl, Kevin Chapman, Tobias Loddenkemper
AIM: To evaluate the efficacy of clobazam treatment in reducing epileptiform discharges and modifying neuropsychological function in continuous spike-wave during slow wave sleep. METHOD: We performed a prospective clinical trial in patients with continuous spike-wave during sleep aged 4 to 10 years. Patients underwent neuropsychological assessment and overnight electroencephalographic monitoring before treatment, and subsequent repeat assessment and overnight electroencephalographic monitoring 3 months after treatment...
November 23, 2017: Developmental Medicine and Child Neurology
https://www.readbyqxmd.com/read/29166838/-express-immunohistochemical-localization-of-ngf-trka-and-p75-in-the-bone-and-articular-cartilage-of-the-mouse-femur
#12
Stephane R Chartier, Stefanie A Mitchell, Lisa A Majuta, Patrick Mantyth
No abstract text is available yet for this article.
January 1, 2017: Molecular Pain
https://www.readbyqxmd.com/read/29164231/storage-of-porcine-cornea-in-an-innovative-bioreactor
#13
Damien Guindolet, Emmanuel Crouzet, Zhiguo He, Pascal Herbepin, Clotilde Jumelle, Chantal Perrache, Jean Marc Dumollard, Fabien Forest, Michel Peoc'h, Philippe Gain, Eric Gabison, Gilles Thuret
Purpose: To quantify cell survival and tissue structure preservation of porcine cornea stored in a bioreactor (BR) that recreates a transcorneal pressure gradient equivalent to intraocular pressure (IOP) and renews the medium. Methods: A BR comprising endothelial and epithelial chambers was machined in a biocompatible material. The porcine cornea, securely held, separated the chambers. Medium flow and pressure inside the endothelial chamber were maintained by a peristaltic pump...
November 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29160151/extracellular-matrix-from-periodontal-ligament-cells-could-induce-the-differentiation-of-induced-pluripotent-stem-cells-to-periodontal-ligament-stem-cell-like-cells
#14
Sayuri Hamano, Atsushi Tomokiyo, Daigaku Hasegawa, Shinichiro Yoshida, Hideki Sugii, Hiromo Mitarai, Shoko Fujino, Naohisa Wada, Hidefumi Maeda
The periodontal ligament (PDL) plays an important role in anchoring teeth in the bone socket. Damage to the PDL, such as following severe inflammation, can be treated with a therapeutic strategy that uses stem cells derived from PDL tissue (PDLSCs), a strategy that has received intense scrutiny over the past decade. However, there is an insufficient number of PDLSCs within the PDL for treating such damage. Therefore, we sought to induce the differentiation of induced pluripotent stem (iPS) cells into PDLSCs as an initial step toward PDL therapy...
November 21, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/29129676/exercise-enhances-cognitive-function-and-neurotrophin-expression-in-the-hippocampus-accompanied-by-changes-in-epigenetic-programming-in-senescence-accelerated-mice
#15
Hiroshi Maejima, Naohiko Kanemura, Takanori Kokubun, Kenji Murata, Kiyomi Takayanagi
Aerobic exercise is known to increase expression of neurotrophins, particularly brain-derived neurotrophic factor (BDNF), in the hippocampus and to improve cognitive function. Exercise exerts neuroprotective effects in the hippocampus by inducing epigenetic changes, which play crucial roles in aging and neurodegenerative diseases. Specifically, the activity levels of histone acetyltransferases (HATs) and histone deacetylases (HDACs) regulate histone acetylation and modulate gene transcription. The objective of the present study was to assess the interactive effects of exercise and aging on cognitive function, expression of neurotrophins (BDNF and neurotrophin-4) and their receptors (tyrosine receptor kinase B and p75), and epigenetic regulations, including the activity of HATs and HADCs in the hippocampus...
November 9, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29127334/biological-assessments-of-multifunctional-hydrogel-decorated-implantable-neural-cuff-electrode-for-clinical-neurology-application
#16
Han-Jun Kim, Dong Nyoung Heo, Yi Jae Lee, Sang Jin Lee, Ji Yoon Kang, Soo Hyun Lee, I I Keun Kwon, Sun Hee Do
The implantable cuff electrode is an effective neuroprosthetic device in current nerve tissue engineering. However, biocompatibility and stability are still a serious dispute in terms of in vivo function and continuous monitoring. In this regard, assessing the host's biological response to biomaterials is one of the key factors of chronic implantation. In this article, we analyzed the peripheral nerve specific-biological responses to the application of multi-functional hydrogel-coated electrodes. The surface of the cuff electrode was modified using a multifunctional hydrogel composed of PEG hydrogel, cyclosporin A(CsA)-microsphere(MS) and electrodeposited PEDOT:PSS...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29121950/the-hiv-1-integrase-ledgf-allosteric-inhibitor-mut-a-resistance-profile-impairment-of-virus-maturation-and-infectivity-but-without-influence-on-rna-packaging-or-virus-immunoreactivity
#17
Céline Amadori, Yme Ubeles van der Velden, Damien Bonnard, Igor Orlov, Nikki van Bel, Erwann Le Rouzic, Laia Miralles, Julie Brias, Francis Chevreuil, Daniele Spehner, Sophie Chasset, Benoit Ledoussal, Luzia Mayr, François Moreau, Felipe García, José Gatell, Alessia Zamborlini, Stéphane Emiliani, Marc Ruff, Bruno P Klaholz, Christiane Moog, Ben Berkhout, Montserrat Plana, Richard Benarous
BACKGROUND: HIV-1 Integrase (IN) interacts with the cellular co-factor LEDGF/p75 and tethers the HIV preintegration complex to the host genome enabling integration. Recently a new class of IN inhibitors was described, the IN-LEDGF allosteric inhibitors (INLAIs). Designed to interfere with the IN-LEDGF interaction during integration, the major impact of these inhibitors was surprisingly found on virus maturation, causing a reverse transcription defect in target cells. RESULTS: Here we describe the MUT-A compound as a genuine INLAI with an original chemical structure based on a new type of scaffold, a thiophene ring...
November 9, 2017: Retrovirology
https://www.readbyqxmd.com/read/29113822/lack-of-tnf-%C3%AE-signaling-through-p55-makes-the-mice-more-susceptible-to-acute-infection-but-does-not-alter-state-of-latency-and-reactivation-of-hsv-1
#18
Aditi Mohankrishnan, Rajesh Parmar, Vishakha Bhurani, Sarat Kumar Dalai
TNF-α has been shown to play an important role in pathogenesis and latency of HSV-1 infections. TNF-α signals through TNFR1 (p55) and TNFR2 (p75), and signaling through p55 generally results in gene activation leading to induction of inflammatory responses. Here, we studied the role of TNF-α signaling in latent virus reactivation in p55-knock out (KO) mouse model of ocular HSV-1 infection. We found that KO mice are more susceptible to HSV-1 infection compared to wild type C57Bl/6 mice. While the absence of TNFRI signaling enhanced the ganglion latent DNA content by two folds, there was no difference in the maintenance and reactivation of latent HSV-1...
November 4, 2017: Virus Research
https://www.readbyqxmd.com/read/29113684/blood-mercury-concentration-fish-consumption-and-anthropometry-in-chinese-children-a-national-study
#19
Zhen-Yan Gao, Min-Ming Li, Ju Wang, Jin Yan, Can-Can Zhou, Chong-Huai Yan
OBJECTIVE: This study sought to obtain national cross-sectional data for blood mercury levels and risk factors for mercury exposure in Chinese children aged 0 to 6years to provide evidence to support preventive measures for reducing childhood blood mercury levels. METHODS: A multi-stage, stratified, clustered random sampling survey was conducted May 2013-Mar 2015. Shanghai, Jilin, Shanxi, Guangdong, Qinghai, Yunnan and Hubei, which are located in seven different geographical regions in China, were selected as the study field...
January 2018: Environment International
https://www.readbyqxmd.com/read/29108999/generation-of-rationally-designed-nerve-growth-factor-ngf-variants-with-receptor-specificity
#20
Laura A Carleton, Reka Chakravarthy, Almer M van der Sloot, Katarzyna Mnich, Luis Serrano, Afshin Samali, Adrienne M Gorman
Nerve growth factor (NGF) is the prototypic member of the neurotrophin family and binds two receptors, TrkA and the 75 kDa neurotrophin receptor (p75(NTR)), through which diverse and sometimes opposing effects are mediated. Using the FoldX protein design algorithm, we generated eight NGF variants with different point mutations predicted to have altered binding to TrkA or p75(NTR). Of these, the I31R NGF variant exhibited specific binding to p75(NTR). The generation of this NGF variant with selective affinity for p75(NTR) can be used to enhance understanding of neurotrophin receptor imbalance in diseases and identifies a key targetable residue for the development of small molecules to disrupt binding of NGF to TrkA with potential uses in chronic pain...
November 3, 2017: Biochemical and Biophysical Research Communications
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