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Jean-Michel Vandeweerd, Fanny Hontoir, Alexis De Knoop, Kathleen De Swert, Charles Nicaise
Phrenic motor neurons are cervical motor neurons originating from C3 to C6 levels in most mammalian species. Axonal projections converge into phrenic nerves innervating the respiratory diaphragm. In spinal cord slices, phrenic motor neurons cannot be identified from other motor neurons on morphological or biochemical criteria. We provide the description of procedures for visualizing phrenic motor neuron cell bodies in mice, following intrapleural injections of cholera toxin subunit beta (CTB) conjugated to a fluorophore...
February 22, 2018: Journal of Visualized Experiments: JoVE
Kavi Devraj, Sylvaine Guérit, Jakranka Macas, Yvonne Reiss
Blood-brain barrier (BBB) is a specialized barrier that protects the brain microenvironment from toxins and pathogens in the circulation and maintains brain homeostasis. The principal sites of the barrier are endothelial cells of the brain capillaries whose barrier function results from tight intercellular junctions and efflux transporters expressed on the plasma membrane. This function is regulated by pericytes and astrocytes that together form the neurovascular unit (NVU). Several neurological diseases such as stroke, Alzheimer's disease (AD), brain tumors are associated with an impaired BBB function...
February 26, 2018: Journal of Visualized Experiments: JoVE
Natasha A Lannin, Louise Ada, Coralie English, Julie Ratcliffe, Maria Crotty
Rationale Although clinical practice guidelines recommend that management of moderate to severe spasticity include the use of botulinum toxin-A in conjunction with therapy, there is currently no evidence to support the addition of therapy. Aims To determine the effect and cost-benefit of adding evidence-based movement training to botulinum toxin-A. Sample size estimate A total of 136 participants will be recruited in order to be able to detect a between-group difference of seven points on the Goal Attainment Scale T-score with 80% power at a two-tailed significance level of 0...
January 1, 2018: International Journal of Stroke: Official Journal of the International Stroke Society
Kate Basley, Dave Goulson
Arable field margins are often sown with wildflowers to encourage pollinators and other beneficial or desirable insects such as bees and butterflies. Concern has been raised that these margins may be contaminated with systemic pesticides such as neonicotinoids used on the adjacent crop, and that this may negatively impact beneficial insects. The use of neonicotinoids has been linked to butterfly declines, and species such as the common blue butterfly ( Polyommatus icarus) that feed upon legumes commonly sown in arable field margins, may be exposed to such toxins...
March 19, 2018: Environmental Science & Technology
István Pócsi, Gábor Király, Gáspár Bánfalvi
Fungal toxins are secondary metabolites, in which many of them were mycotoxins, affecting eukaryotic cells with a broad range of structural and functional variety contributing to the multitude of their classification. This refers to the harmful genotoxic (mutagenic, teratogenic, and carcinogenic) effects of mycotoxins on the one hand, and their cytocidic and antineoplastic properties on the other hand. This "double edged sword" effect could be utilized against the spread of tumors in older patients when the survival is much more important than the mutagenic side effects...
March 19, 2018: Acta Microbiologica et Immunologica Hungarica
Rosalia Crupi, Daniela Impellizzeri, Marika Cordaro, Rosalba Siracusa, Giovanna Casili, Maurizio Evangelista, Salvatore Cuzzocrea
Parkinson's disease (PD) is a neurodegenerative disease characterized by degeneration of dopaminergic neurons. Aging is a major risk factor for idiopathic PD. Several prior studies examined the neuroprotective effects of palmitoylethanolamide (PEA), alone or combined with antioxidants, in a model of PD induced by the dopaminergic toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Here, we analyzed the pretreatment effect of micronized PEA (PEAm) on neuroinflammation and neuronal cell death in the MPTP model...
March 19, 2018: Molecular Neurobiology
Kristy Pilbeam, Hongbo Wang, Elizabeth Taras, Rachel J Bergerson, Brianna Ettestad, Todd DeFor, Antonella Borgatti, Daniel A Vallera, Michael R Verneris
Children with high risk sarcoma have a poor prognosis despite surgical resection, irradiation and chemotherapy. Alternative therapies are urgently needed. Urokinase-type plasminogen activator receptor (uPAR) and epidermal growth factor receptor (EGFR) are surface proteins expressed by some pediatric sarcomas. We show for the first time that a de-immunized bispecific ligand toxin, EGFATFKDEL, directed against EGFR and uPAR, successfully targets pediatric sarcoma. Using flow cytometry, we identified a rhabdomyosarcoma (RMS) cell line, RH30, that expresses both uPAR and EGFR, and a Ewing sarcoma (EWS) cell line, TC-71, that expresses only uPAR...
February 23, 2018: Oncotarget
Pakpoom Boonchuen, Phattarunda Jaree, Anchalee Tassanakajon, Kunlaya Somboonwiwat
Acute hepatopancreatic necrosis disease, AHPND, caused by a specific strain of Vibrio parahaemolyticus (VPAHPND ), results in great loss of global shrimp production. Despite this, studies on shrimp defense mechanisms protecting against AHPND are few. In this study, suppression subtractive hybridization (SSH) was performed to identify differentially expressed genes from white shrimp Litopenaeus vannamei hepatopancreas upon VPAHPND infection at the early stages: 3 and 6 h post challenge and in the late stage at 48 h post challenge...
March 15, 2018: Developmental and Comparative Immunology
Juan C Santos, Rebecca D Tarvin, Lauren A O'Connell, David C Blackburn, Luis A Coloma
Symbionts (e.g., endoparasites and commensals) play an integral role in their host's ecology, yet in many cases their diversity is likely underestimated. Although endoparasites are traditionally characterized using morphology, sequences of conserved genes, and shotgun metagenomics, host transcriptomes constitute an underused resource to identify these organisms' diversity. By isolating non-host transcripts from host transcriptomes, individual host tissues can now simultaneously reveal their endoparasite species richness (i...
March 15, 2018: Molecular Phylogenetics and Evolution
Sean Doyle, Gary W Jones, Stephen K Dolan
Gliotoxin is an epipolythiodioxopiperazine (ETP) class toxin, contains a disulfide bridge that mediates its toxic effects via redox cycling and is produced by the opportunistic fungal pathogen Aspergillus fumigatus. The gliotoxin bis-thiomethyltransferase, GtmA, attenuates gliotoxin biosynthesis in A. fumigatus by conversion of dithiol gliotoxin to bis-thiomethylgliotoxin (BmGT). Here we show that disruption of dithiol gliotoxin bis-thiomethylation functionality in A. fumigatus results in significant remodelling of the A...
April 2018: Fungal Biology
Alexander Kyrychenko, Nathan M Lim, Victor Vasquez-Montes, Mykola V Rodnin, J Alfredo Freites, Linh P Nguyen, Douglas J Tobias, David L Mobley, Alexey S Ladokhin
Dynamic disorder of the lipid bilayer presents a challenge for establishing structure-function relationships in membranous systems. The resulting structural heterogeneity is especially evident for peripheral and spontaneously inserting membrane proteins, which are not constrained by the well-defined transmembrane topology and exert their action in the context of intimate interaction with lipids. Here, we propose a concerted approach combining depth-dependent fluorescence quenching with Molecular Dynamics simulation to decipher dynamic interactions of membrane proteins with the lipid bilayers...
March 17, 2018: Journal of Membrane Biology
J J Pytko-Polonczyk, A Jakubik, A Przeklasa-Bierowiec, B Muszynska
Examination of dental materials and their properties at the initial stage of the digestive process requires the development of conditions that mimic the environment of the oral cavity. One of the main components of this area is saliva, where many reactions occur under natural conditions. Human saliva is an important physiological fluid that is essential for the maintenance of good oral health and of the entire human body; it is the place where digestion begins and thus contributes to the supply of those nutrients and health-promoting substances that are essential to the body but may also cause release of potential toxins...
December 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
Xiangyang Liu, Lucas Farnung, Christoph Wigge, Patrick Cramer
RNA polymerase II (Pol II) is the central enzyme that transcribes eukaryotic protein-coding genes to produce mRNA. The mushroom toxin α-amanitin binds Pol II and inhibits transcription at the step of RNA chain elongation. Pol II from yeast binds α-amanitin with micromolar affinity, whereas metazoan Pol II enzymes exhibit nanomolar affinities. Here, we present the high-resolution cryo-EM structure of α-amanitin bound to and inhibited by its natural target, the mammalian Pol II elongation complex. The structure revealed that the toxin is located in a pocket previously identified in yeast Pol II, but forms additional contacts with metazoan-specific residues, which explain why its affinity to mammalian Pol II is ~3000 times higher than for yeast Pol II...
March 17, 2018: Journal of Biological Chemistry
Navneet Ammal Kaidery, Bobby Thomas
Parkinson's disease (PD) is one of the most common neurodegenerative movement disorder characterized by preferential loss of dopaminergic neurons of the substantia nigra pars compacta and the presence of Lewy bodies containing α-synuclein. Although the cause of PD remains elusive, remarkable advances have been made in understanding the possible causative mechanisms of PD pathogenesis. An explosion of discoveries during the past two decades has led to the identification of several autosomal dominant and recessive genes that cause familial forms of PD...
March 14, 2018: Neurochemistry International
Joanna A Ruszkiewicz, Adi Pinkas, Mahfuzur R Miah, Rebecca L Weitz, Michael J A Lawes, Ayodele J Akinyemi, Omamuyovwi M Ijomone, Michael Aschner
Due to many advantages Caenorhabditis elegans (C. elegans) has become a preferred model of choice in many fields, including neurodevelopmental toxicity studies. This review discusses the benefits of using C. elegans as an alternative to mammalian systems and gives examples of the uses of the nematode in evaluating the effects of major known neurodevelopmental toxins, including manganese, mercury, lead, fluoride, arsenic and organophosphorus pesticides. Reviewed data indicates numerous similarities with mammals in response to these toxins...
March 14, 2018: Toxicology and Applied Pharmacology
Kamilla A Mukhutdinova, Marat R Kasimov, Arthur R Giniatullin, Guzel F Zakyrjanova, Alexey M Petrov
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the initial denervation of skeletal muscle and subsequent death of motor neurons. A dying-back pattern of ALS suggests a crucial role for neuromuscular junction dysfunction. In the present study, microelectrode recording of postsynaptic currents and optical detection of synaptic vesicle traffic (FM1-43 dye) and intracellular NO levels (DAF-FM DA) were used to examine the effect of the major brain-derived cholesterol metabolite 24S-hydroxycholesterol (24S-HC, 0...
March 14, 2018: Molecular and Cellular Neurosciences
Yu Chen, Zhen Li, Zhu Xu, Huanyin Tang, Wenxuan Guo, Xiaoxiang Sun, Wenjun Zhang, Jian Zhang, Xiaoping Wan, Ying Jiang, Zhiyong Mao
The homologous recombination (HR) pathway is a promising target for cancer therapy as it is frequently upregulated in tumors. One such strategy is to target tumors with cancer-specific, hyperactive promoters of HR genes including RAD51 and RAD51C. However, the promoter size and the delivery method have limited its potential clinical applications. Here we identified the ~2.1 kb promoter of XRCC2, similar to ~6.5 kb RAD51 promoter, as also hyperactivated in cancer cells. We found that XRCC2 expression is upregulated in nearly all types of cancers, to a degree comparable to RAD51 while much higher than RAD51C...
March 16, 2018: Cell Death & Disease
Babak Barati, Firouz Ebrahimi, Shahram Nazarian
BACKGROUND: Cholera toxin (CT), responsible for the harmful effects of cholera infection, is made up of one A subunit (enzymatic), and five B subunits (cell binding). The release of cholera toxin is the main reason for the debilitating loss of intestinal fluid. Inhibition of the B subunit (CTB) may block CT activity. OBJECTIVE: To determine the effect of anti CTB-IgY against oral challenge with V. cholera in suckling infant mice. METHODS: The binding domain of cholera toxin was amplified and ligated into pET28a vector...
March 2018: Iranian Journal of Immunology: IJI
Mark R H Hurst, Amy Beattie, Sandra A Jones, Aurelie Laugraud, Chikako van Koten, Lincoln Harper
A highly virulent Serratia proteamaculans strain, AGR96X, exhibiting specific pathogenicity against larvae of the New Zealand grass grub ( Costelytra giveni ; Coleoptera: Scarabaeidae) and the New Zealand manuka beetle ( Pyronota festiva and P. setosa ; Coleoptera: Scarabaeidae), was isolated from a diseased grass grub larva. A 12-day median lethal dose of 4.89 ± 0.92 × 103 cells per grass grub larva was defined for AGR96X, and death occurred within 5--12 days following ingestion of a high bacterial dose...
March 16, 2018: Applied and Environmental Microbiology
Maria Emilia Isolani, Renata Batistoni, Chiara Ippolito, Anna Maria Bianucci, Silvia Marracci, Leonardo Rossi
Planarian flatworms possess extraordinary regenerative capability and body plasticity, which rely on a composite population of stem cells, the neoblasts. Despite impressive advances have been recently achieved in the knowledge of neoblast biology, few is still known about factors that are released by differentiated tissues and influence the neoblast fate. Extracellular matrix (ECM) is a fundamental component of the stem cell niche and its remodeling affects stem cell fate. Here we provide the characterization of the astacin gene family of metalloproteinases in planarians, good candidate enzymes for generating dynamicity in the ECM...
March 13, 2018: Gene Expression Patterns: GEP
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