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https://www.readbyqxmd.com/read/29773600/the-interleukin-3-receptor-cd123-targeted-sl-401-mediates-potent-cytotoxic-activity-against-cd34-cd123-cells-from-acute-myeloid-leukemia-myelodysplastic-syndrome-patients-and-healthy-donors
#1
Rajeswaran Mani, Swagata Goswami, Bhavani Gopalakrishnan, Rahul Ramaswamy, Ronni Wasmuth, Minh Tranh, Xiaokui Mo, Amber Gordon, Donna Bucci, David M Lucas, Alice Mims, Christopher Brooks, Adrienne Dorrance, Alison Walker, William Blum, John C Byrd, Gerard Lozanski, Sumithira Vasu, Natarajan Muthusamy
Diseases with clonal hematopoiesis such as myelodysplastic syndrome and acute myeloid leukemia have high rates of relapse. Only a small subset of acute myeloid leukemia patients are cured with chemotherapy alone. Relapse in these diseases occurs at least in part due to the failure to eradicate leukemic stem cells or hematopoietic stem cells in myelodysplastic syndrome. CD123, the alpha chain of the interleukin-3 receptor heterodimer, is expressed on the majority of leukemic stem cells and myelodysplastic syndrome hematopoietic stem cells and in 80% of acute myeloid leukemia...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29772703/alpha-mangostin-improves-insulin-secretion-and-protects-ins-1-cells-from-streptozotocin-induced-damage
#2
Dahae Lee, Young-Mi Kim, Kiwon Jung, Young-Won Chin, Ki Sung Kang
Alpha (α)-mangostin, a yellow crystalline powder with a xanthone core structure, is isolated from mangosteen ( Garcinia mangostana ), which is a tropical fruit of great nutritional value. The aim of the present study was to investigate the anti-diabetic effects of α-mangostin and to elucidate the molecular mechanisms underlying its effect on pancreatic beta (β)-cell dysfunction. To assess the effects of α-mangostin on insulin production, rat pancreatic INS-1 cells were treated with non-toxic doses of α-mangostin (1⁻10 μM) and its impact on insulin signaling was examined by Western blotting...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29754498/axonal-guidance-signaling-pathway-is-suppressed-in-human-nasal-polyps
#3
Dawei Wu, Sarina K Mueller, Angela L Nocera, Kristen Finn, Towia A Libermann, Benjamin S Bleier
Background Dysfunctional innervation might contribute to the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP), but the state of the axonal outgrowth signaling in CRSwNP is unknown. The purpose of this study was to explore the axonal outgrowth pathway-related protein expression in CRSwNP. Methods Institutional review board approved study in which tissue proteomes were compared between control and CRSwNP patients (n = 10/group) using an aptamer-based proteomic array and confirmed by whole transcriptomic analysis...
January 1, 2018: American Journal of Rhinology & Allergy
https://www.readbyqxmd.com/read/29723951/pharmacological-cyclophilin-inhibitors-prevent-intoxication-of-mammalian-cells-with-bordetella-pertussis-toxin
#4
Katharina Ernst, Nina Eberhardt, Ann-Katrin Mittler, Michael Sonnabend, Anna Anastasia, Simon Freisinger, Cordelia Schiene-Fischer, Miroslav Malešević, Holger Barth
The Bordetella pertussis toxin (PT) is one important virulence factor causing the severe childhood disease whooping cough which still accounted for approximately 63,000 deaths worldwide in children in 2013. PT consists of PTS1, the enzymatically active (A) subunit and a non-covalently linked pentameric binding/transport (B) subunit. After endocytosis, PT takes a retrograde route to the endoplasmic reticulum (ER), where PTS1 is released into the cytosol. In the cytosol, PTS1 ADP-ribosylates inhibitory alpha subunits of trimeric GTP-binding proteins (Giα) leading to increased cAMP levels and disturbed signalling...
May 1, 2018: Toxins
https://www.readbyqxmd.com/read/29714014/epitope-mapping-using-yeast-display-and-next-generation-sequencing
#5
Thomas Van Blarcom, Andrea Rossi, Davide Foletti, Purnima Sundar, Steven Pitts, Zea Melton, Dilduz Telman, Lora Zhao, Wai Ling Cheung, Jan Berka, Wenwu Zhai, Pavel Strop, Jaume Pons, Arvind Rajpal, Javier Chaparro-Riggers
Monoclonal antibodies are the largest class of therapeutic proteins due in part to their ability to bind an antigen with a high degree of affinity and specificity. A precise determination of their epitope is important for gaining insights into their therapeutic mechanism of action and to help differentiate antibodies that bind the same antigen. Here, we describe a method to precisely and efficiently map the epitopes of multiple antibodies in parallel over the course of just several weeks. This approach is based on a combination of rational library design, yeast surface display, and next generation DNA sequencing and provides quantitative insights into the epitope residues most critical for the antibody-antigen interaction...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29712570/il-1%C3%AE-suppresses-cltp-induced-surface-expression-of-glua1-and-actin-polymerization-via-ceramide-mediated-src-activation
#6
Liqi Tong, G Aleph Prieto, Carl W Cotman
BACKGROUND: Brain inflammation including increases in inflammatory cytokines such as IL-1β is widely believed to contribute to the pathophysiology of Alzheimer's disease. Although IL-1β-induced impairments in long-term potentiation (LTP) in acute hippocampal slices and memory functions in vivo have been well documented, the neuron-specific molecular mechanisms of IL-1β-mediated impairments of LTP and memory remain unclear. METHODS: This study uses an in vitro approach in primary hippocampal neurons to evaluate the effect of IL-1β on chemical LTP (cLTP)-induced structural plasticity and signaling...
April 30, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29701674/development-of-an-analytical-method-for-simultaneous-determination-of-the-modified-forms-of-4-15-diacetoxyscirpenol-and-their-occurrence-in-japanese-retail-food
#7
Tomoya Yoshinari, Nanami Takeda, Maiko Watanabe, Yoshiko Sugita-Konishi
4,15-Diacetoxyscirpenol (4,15-DAS) is a type A trichothecene mycotoxin produced by Fusarium species. Four modified forms of 4,15-DAS including 7-hydroxydiacetoxyscirpenol, 7,8-dihydroxydiacetoxyscirpenol, 4β,8α,15-triacetoxy-3α,7α-dihydroxy-12,13-epoxytrichothec-9-ene and 4,15-diacetylnivalenol were purified from cultures of F. equiseti . An analytical method using a multifunctional column has been developed for the simultaneous determination of 4,15-DAS, its four modified forms, T-2 toxin, HT-2 toxin and neosolaniol in cereals...
April 26, 2018: Toxins
https://www.readbyqxmd.com/read/29677133/modified-fusarium-mycotoxins-in-cereals-and-their-products-metabolism-occurrence-and-toxicity-an-updated-review
#8
REVIEW
Marcin Bryła, Agnieszka Waśkiewicz, Edyta Ksieniewicz-Woźniak, Krystyna Szymczyk, Renata Jędrzejczak
Mycotoxins are secondary fungal metabolites, toxic to humans, animals and plants. Under the influence of various factors, mycotoxins may undergo modifications of their chemical structure. One of the methods of mycotoxin modification is a transformation occurring in plant cells or under the influence of fungal enzymes. This paper reviews the current knowledge on the natural occurrence of the most important trichothecenes and zearalenone in cereals/cereal products, their metabolism, and the potential toxicity of the metabolites...
April 20, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29664124/a-comparison-of-the-treatment-recommendations-for-neurogenic-lower-urinary-tract-dysfunction-in-the-national-institute-for-health-and-care-excellence-european-association-of-urology-and-international-consultations-on-incontinence-guidelines
#9
Ashley Jaggi, Marcus Drake, Emad Siddiqui, Francis Fatoye
AIMS: Healthcare guidelines are an important vehicle in establishing up-to-date evidence based medicine (EBM) in clinical practice. Due to varying development processes, clinical guidelines created by different institutions can often contain contrasting recommendations. This can have implications for optimal and standardized patient care across management settings. METHODS: The similarities and differences of treatment recommendations made in the National Institute for Health and Care Excellence (NICE), The European Association of Urology (EAU), and the International Consultation on Continence (ICI) guidelines for neurogenic lower urinary tract dysfunction (NLUTD) were assessed...
April 17, 2018: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/29659477/alpha-toxin-contributes-to-biofilm-formation-among-staphylococcus-aureus-wound-isolates
#10
Michele J Anderson, Emily Schaaf, Laura M Breshears, Heidi W Wallis, James R Johnson, Christine Tkaczyk, Bret R Sellman, Jisun Sun, Marnie L Peterson
Biofilms complicate treatment of Staphylococcus aureus (SA) wound infections. Previously, we determined alpha-toxin (AT)-promoted SA biofilm formation on mucosal tissue. Therefore, we evaluated SA wound isolates for AT production and biofilm formation on epithelium and assessed the role of AT in biofilm formation. Thirty-eight wound isolates were molecularly typed by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (ST), and spa typing. We measured biofilm formation of these SA isolates in vitro and ex vivo and quantified ex vivo AT production...
April 16, 2018: Toxins
https://www.readbyqxmd.com/read/29649418/roles-of-progesterone-receptor-membrane-component-1-and-membrane-progestin-receptor-alpha-in-regulation-of-zebrafish-oocyte-maturation
#11
Joseph Aizen, Yefei Pang, Caleb Harris, Aubrey Converse, Yong Zhu, Meagan A Aguirre, Peter Thomas
Although previous studies suggest membrane progesterone receptor alpha (mPRα/Paqr7) mediates 17, 20β-dihydroxy-4-pregnen-3-one (DHP) induction of oocyte maturation (OM) in zebrafish, critical information needed to establish mPRα as the receptor mediating OM, is lacking. The relative potencies of progestins and specific mPRα agonists in inducing OM matched their relative binding affinities for zebrafish mPRα, supporting its role in OM. Microinjection of pertussis toxin blocked DHP induction of OM and the progestin-induced decrease in cyclic AMP levels, suggesting mPRα activates an inhibitory G protein (Gi)...
April 9, 2018: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/29626299/short-chain-consensus-alpha-neurotoxin-a-synthetic-60-mer-peptide-with-generic-traits-and-enhanced-immunogenic-properties
#12
Guillermo de la Rosa, Ligia L Corrales-García, Ximena Rodriguez-Ruiz, Estuardo López-Vera, Gerardo Corzo
The three-fingered toxin family and more precisely short-chain α-neurotoxins (also known as Type I α-neurotoxins) are crucial in defining the elapid envenomation process, but paradoxically, they are barely neutralized by current elapid snake antivenoms. This work has been focused on the primary structural identity among Type I neurotoxins in order to create a consensus short-chain α-neurotoxin with conserved characteristics. A multiple sequence alignment considering the twelve most toxic short-chain α-neurotoxins reported from the venoms of the elapid genera Acanthophis, Oxyuranus, Walterinnesia, Naja, Dendroaspis and Micrurus led us to propose a short-chain consensus α-neurotoxin, here named ScNtx...
April 6, 2018: Amino Acids
https://www.readbyqxmd.com/read/29617297/the-combinational-use-of-crispr-cas9-and-targeted-toxin-technology-enables-efficient-isolation-of-bi-allelic-knockout-non-human-mammalian-clones
#13
Satoshi Watanabe, Takayuki Sakurai, Shingo Nakamura, Kazuchika Miyoshi, Masahiro Sato
Recent advances in genome editing systems such as clustered regularly interspaced short palindromic repeats/CRISPR-associated protein-9 nuclease (CRISPR/Cas9) have facilitated genomic modification in mammalian cells. However, most systems employ transient treatment with selective drugs such as puromycin to obtain the desired genome-edited cells, which often allows some untransfected cells to survive and decreases the efficiency of generating genome-edited cells. Here, we developed a novel targeted toxin-based drug-free selection system for the enrichment of genome-edited cells...
April 4, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29617191/alpha-galactosylceramide-%C3%AE-galcer-enhances-vaccine-induced-protection-in-a-model-of-ricin-intoxication
#14
Jennifer L Yates, Elizabeth Leadbetter, Nicholas J Mantis
Alpha-galactosylceramide (αGalCer) is a glycolipid derived from a marine sponge that is a potent activator of both mouse and human invariant natural killer T (iNKT) cells. For that reason, αGalCer is a promising vaccine adjuvant that has been shown to improve both humoral and cellular immunity when co-administered with various vaccines, including candidate vaccines for biodefense. In the current study, we tested the effectiveness of αGalCer as an adjuvant for the clinically-relevant ricin toxin subunit vaccine, RiVax...
April 4, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29568025/are-pharmacological-treatments-for-oro-facial-pain-effective
#15
Debra Fischoff, Silvia Spivakovsky
Data sourcesElectronic searches of PubMed, the Cochrane Library, Embase, the National Health Service Economic Evaluation Database and HTA until March 2017. Also handsearched referenced in the original articles. Grey literature was not included.Study selectionRandomised controlled trials with more than ten participants with oro-facial pain duration of more than three months were sub grouped into: TMD-muscle pain (TMD-m), TMD-joint pain (TMD-j), burning mouth syndrome (BMS) and other oro-facial pain. Studies include any pharmacological treatment against another pharmacological, non-pharmacological treatment, placebo or no treatment...
March 23, 2018: Evidence-based Dentistry
https://www.readbyqxmd.com/read/29564531/shaker-related-voltage-gated-potassium-channels-kv1-in-human-hippocampus
#16
Michael Willis, Irmgard Leitner, Klaus Seppi, Maria Trieb, Georg Wietzorrek, Josef Marksteiner, Hans-Günther Knaus
In this study, we investigated the tissue expression levels, alpha subunit composition and distribution of Shaker-related voltage-dependent potassium Kv1 channels in human hippocampus by combining western blotting experiments, toxin autoradiography, in vivo radioligand binding studies, immunoprecipitation and immunohistochemistry. Tissue expression of Kv1.1 and Kv1.2 α-subunits in human post-mortem brain tissue was confirmed in immunoblot analysis using a panel of specific monoclonal and polyclonal antibodies...
March 21, 2018: Brain Structure & Function
https://www.readbyqxmd.com/read/29558726/detection-of-salivary-protein-biomarkers-of-saliva-secretion-disorder-in-a-primary-sj%C3%A3-gren-syndrome-murine-model
#17
Peisheng Liang, Wangyong Zhu, Tianjun Lan, Qian Tao
Saliva secretion disorder is one of the most common symptoms in primary Sjögren syndrome (pSS). Salivary biomarkers related to saliva secretion disorder were identified in a pSS murine model, NOD/ShiLtJ mouse, using differential proteomic analysis. Candidate biomarkers were screened with Kyoto Encyclopedia of Genes and Genomes pathway analysis and validated in saliva and salivary glands by western blotting and immunohistochemistry (IHC). Biological functions were detected using ingenuity pathway analysis (IPA)...
March 12, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29526827/toxin-profile-of-fecal-clostridium-perfringens-strains-isolated-from-children-with-autism-spectrum-disorders
#18
Bartłomiej Góra, Zygmunt Gofron, Magdalena Grosiak, Małgorzata Aptekorz, Beata Kazek, Piotr Kocelak, Halina Radosz-Komoniewska, Jerzy Chudek, Gayane Martirosian
Infectious factors are taken into consideration in pathophysiology of autism spectrum disorders (ASD). ASD patients often suffer from gastrointestinal disorders. The intestinal microbiota of autistic patients significantly differs from that in healthy individuals. The aim of the study was to compare the profile of toxins produced by C. perfringens strains isolated from feces of children with ASD, with healthy individuals and obese subjects. This study included 111 strains of C. perfringens: 49 isolates from 29 children with ASD, 30 - from 17 healthy individuals and 32 - from 24 young obese subjects...
March 8, 2018: Anaerobe
https://www.readbyqxmd.com/read/29524545/expression-of-the-alpha-toxin-of-clostridium-perfringens-in-lactobacillus-casei-genome-and-evaluation-of-its-immune-effects-in-mice
#19
Baifen Song, Hongyu Cui, Longzhu Ju, Li Song, Lijie Tang, Yijing Li
We previously developed a stable and marker-free Lactobacillus casei strain (PPαT Δupp) that contained a chromosomally integrated expression cassette (PPαT) that enabled the surface expression of the Clostridium perfringens alpha toxin. To measure immune responses against the alpha toxin, specific-pathogen-free BALB/c mice were inoculated with L. casei PPαT Δupp by oral gavage. Then, specific immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies and cytokines were measured by enzyme-linked immunosorbent assay (ELISA) and flow cytometry (FCM)...
March 7, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29491391/disruption-of-the-open-conductance-in-the-%C3%AE-tongue-mutants-of-cytolysin-a
#20
Monifa A Fahie, Lucas Liang, Alzira R Avelino, Bach Pham, Patanachai Limpikirati, Richard W Vachet, Min Chen
Cytolysin A (ClyA) is a water-soluble alpha pore-forming toxin that assembles to form an oligomeric pore on host cell membranes. The ClyA monomer possesses an α-helical bundle with a β-sheet subdomain (the β-tongue) previously believed to be critical for pore assembly and/or insertion. Oligomerization of ClyA pores transforms the β-tongue into a helix-turn-helix that embeds into the lipid bilayer. Here, we show that mutations of the β-tongue did not prevent oligomerization or transmembrane insertion. Instead, β-tongue substitution mutants yielded pores with decreased conductance while a deletion mutation resulted in pores that rapidly closed following membrane association...
February 28, 2018: Scientific Reports
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