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https://www.readbyqxmd.com/read/28727722/an-attenuated-shigella-mutant-lacking-the-rna-binding-protein-hfq-provides-cross-protection-against-shigella-strains-of-broad-serotype
#1
Jiro Mitobe, Ritam Sinha, Soma Mitra, Dhrubajyoti Nag, Noriko Saito, Ken Shimuta, Nobuo Koizumi, Hemanta Koley
Few live attenuated vaccines protect against multiple serotypes of bacterial pathogen because host serotype-specific immune responses are limited to the serotype present in the vaccine strain. Here, immunization with a mutant of Shigella flexneri 2a protected guinea pigs against subsequent infection by S. dysenteriae type 1 and S. sonnei strains. This deletion mutant lacked the RNA-binding protein Hfq leading to increased expression of the type III secretion system via loss of regulation, resulting in attenuation of cell viability through repression of stress response sigma factors...
July 20, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28723387/sigma-1-receptor-activation-modifies-intracellular-calcium-exchange-in-the-g93a-hsod1-als-model
#2
Vedrana Tadić, Ayse Malci, Nadine Goldhammer, Beatrice Stubendorff, Saikata Sengupta, Tino Prell, Silke Keiner, Jingyu Liu, Madlen Guenther, Christiane Frahm, Otto W Witte, Julian Grosskreutz
Aberrations in intracellular calcium (Ca(2+)) have been well established within amyotrophic lateral sclerosis (ALS), a severe motor neuron disease. Intracellular Ca(2+) concentration is controlled in part through the endoplasmic reticulum (ER) mitochondria Ca(2+) cycle (ERMCC). The ER supplies Ca(2+) to the mitochondria at close contacts between the two organelles, i.e. the mitochondria-associated ER membranes (MAMs). The Sigma 1 receptor (Sig1R) is enriched at MAMs, where it acts as an inter-organelle signaling modulator...
July 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/28716934/sigma-1-receptors-control-immune-driven-peripheral-opioid-analgesia-during-inflammation-in-mice
#3
Miguel A Tejada, Angeles Montilla-García, Shane J Cronin, Domagoj Cikes, Cristina Sánchez-Fernández, Rafael González-Cano, M Carmen Ruiz-Cantero, Josef M Penninger, José M Vela, José M Baeyens, Enrique J Cobos
Sigma-1 antagonism potentiates the antinociceptive effects of opioid drugs, so sigma-1 receptors constitute a biological brake to opioid drug-induced analgesia. The pathophysiological role of this process is unknown. We aimed to investigate whether sigma-1 antagonism reduces inflammatory pain through the disinhibition of the endogenous opioidergic system in mice. The selective sigma-1 antagonists BD-1063 and S1RA abolished mechanical and thermal hyperalgesia in mice with carrageenan-induced acute (3 h) inflammation...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28711894/-markers-of-dental-children-s-health-in-the-application-of-therapeutic-orthodontic-equipment
#4
Аліса В Пачевська, Аліна В Білошицька
INTRODUCTION: Treatment of teeth anomalies using removable and non-removable orthodontic devices in children leads to complications such as caries, gingivitis, periodontitis, oral mucosa hyperplasia. Etiopathogenetical of these diseases can be associated with biochemical changes in the composition of saliva. AIM: To determine the activity of lysozyme and amylase in oral fluid in children when using a fixed and removable orthodontic devices. MATERIALS AND METHODS: Amylase and lysozyme were studied in oral fluid...
2017: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28702490/sigma-2-receptor-ligands-qsar-model-dataset
#5
Antonio Rescifina, Giuseppe Floresta, Agostino Marrazzo, Carmela Parenti, Orazio Prezzavento, Giovanni Nastasi, Maria Dichiara, Emanuele Amata
The data have been obtained from the Sigma-2 Receptor Selective Ligands Database (S2RSLDB) and refined according to the QSAR requirements. These data provide information about a set of 548 Sigma-2 (σ2) receptor ligands selective over Sigma-1 (σ1) receptor. The development of the QSAR model has been undertaken with the use of CORAL software using SMILES, molecular graphs and hybrid descriptors (SMILES and graph together). Data here reported include the regression for σ2 receptor pKi QSAR models. The QSAR model was also employed to predict the σ2 receptor pKi values of the FDA approved drugs that are herewith included...
August 2017: Data in Brief
https://www.readbyqxmd.com/read/28700244/targeted-yttrium-89-doxorubicin-drug-eluting-bead-a-safety-and-feasibility-pilot-study-in-a-rabbit-liver-cancer-model
#6
Johannes M Ludwig, Minzhi Xing, Yongkang Gai, Lingyi Sun, Dexing Zeng, Hyun S Kim
PURPOSE: To evaluate feasibility and safety of the cancer targeting (Radio)-Chemoembolization drug eluting bead (TRCE-DEB) concept drug SW43-DOX-L-NETA(89Y) DEB for the intra-arterial treatment of VX2 rabbit liver tumors. The treatment compound comprises of the Sigma-2 receptor ligand SW43 for cancer targeting, Doxorubicin (DOX), and 89Yttrium (89Y) as non-radioactive surrogate for therapeutic (Yttrium-90, Lutetium-177) and imaging (Yttrium-86) radioisotopes via the chelator L-NETA. MATERIAL AND METHODS: Ten New Zealand white rabbits with VX2 tumor allografts were used...
July 12, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28691976/distinct-lipoprotein-curves-in-normal-weight-overweight-and-obese-children-and-adolescents
#7
Hagar Interator, Yael Lebenthal, Moshe Hoshen, Inbar Safra, Ran Balicer, Moshe Leshno, Raanan Shamir
OBJECTIVES: Pediatric lipoprotein curves are based on population-based samples. As obesity, may alter lipoprotein levels, cut-offs not adjusted for body mass index (BMI) are potentially inappropriate. We aimed to develop distinct serum lipid curves based on sex and BMI-percentiles for children and adolescents. METHODS: Cross-sectional analysis included all healthy children and adolescents (age range 2-17 years) with available serum lipid concentrations (n = 152,820 of approximately 1...
July 6, 2017: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28687423/an-increase-of-sigma-1-receptor-in-the-penumbra-neuron-after-acute-ischemic-stroke
#8
Xiaotian Zhang, Fangfang Wu, Yun Jiao, Tianyu Tang, Li Yang, Chunqiang Lu, Yanhong Zhang, Yuan Zhang, Ying Bai, Jie Chao, Gaojun Teng, Honghong Yao
BACKGROUND: Penumbra salvage from infarction by early reperfusion within the time window is the target of acute ischemic stroke therapies. Although the penumbral imaging is potently usable in clinic trial, additional work needs to be performed to advancing the field with better-defined, evaluated, and validated imaging measures. METHODS: Mice were subjected to permanent stroke by right middle cerebral artery (MCA) occlusion. Multimodel magnetic resonance imaging (MRI) method was assessed to define the penumbra as that brain region in which the perfusion and diffusion-weighted MR images are mismatched (perfusion-weighted imaging [PWI]-diffusion-weighted imaging [DWI] mismatch)...
July 4, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/28682953/role-of-sigma-1-receptor-p38-mapk-inhibition-in-acupoint-catgut-embedding-mediated-analgesic-effects-in-complete-freund-s-adjuvant-induced-inflammatory-pain
#9
Kairong Du, Xue Wang, Laiting Chi, Wenzhi Li
BACKGROUND: The endoplasmic reticulum chaperone protein Sigma-1 receptor (Sig-1 R) and mitogen-activated protein kinases (MAPKs) are involved in the mechanism of pain. Acupoint stimulation exerts an exact antihyperalgesic effect in inflammatory pain. However, whether Sig-1 R and MAPKs are associated with the acupoint stimulation-induced analgesic effects is not clear. This study investigated the analgesic effect of acupoint catgut embedding (ACE) and the inhibition of Sig-1 R and MAPKs in ACE analgesia...
August 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28674608/experiences-with-lean-six-sigma-as-improvement-strategy-to-reduce-parenteral-medication-administration-errors-and-associated-potential-risk-of-harm
#10
Afke van de Plas, Mariëlle Slikkerveer, Saskia Hoen, Rick Schrijnemakers, Johanna Driessen, Frank de Vries, Patricia van den Bemt
In this controlled before-after study the effect of improvements, derived from Lean Six Sigma strategy, on parenteral medication administration errors and the potential risk of harm was determined. During baseline measurement, on control versus intervention ward, at least one administration error occurred in 14 (74%) and 6 (46%) administrations with potential risk of harm in 6 (32%) and 1 (8%) administrations. Most administration errors with high potential risk of harm occurred in bolus injections: 8 (57%) versus 2 (67%) bolus injections were injected too fast with a potential risk of harm in 6 (43%) and 1 (33%) bolus injections on control and intervention ward...
2017: BMJ Quality Improvement Reports
https://www.readbyqxmd.com/read/28674070/bacillus-subtilis-intramembrane-protease-rasp-activity-in-escherichia-coli-and-in-vitro
#11
Daniel Parrell, Yang Zhang, Sandra Olenic, Lee Kroos
RasP is a predicted intramembrane metalloprotease of Bacillus subtilis that has been proposed to cleave the stress response anti-sigma factors RsiW and RsiV, the cell division protein FtsL, and remnant signal peptides, within their transmembrane segments. To provide evidence for direct effects of RasP on putative substrates, we developed a heterologous coexpression system. Since expression of catalytically-inactive RasP E21A inhibited expression of other membrane proteins in Escherichia coli, we added extra transmembrane segments to RasP E21A, which allowed accumulation of most other membrane proteins...
July 3, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28667101/sigmar1-regulates-endoplasmic-reticulum-stress-induced-c-ebp-homologous-protein-chop-expression-in-cardiomyocytes
#12
Shafiul Alam, Chowdhury S Abdullah, Richa Aishwarya, A Wayne Orr, James Traylor, Sumitra Miriyala, Manikandan Panchatcharam, Christopher B Pattillo, Md Shenuarin Bhuiyan
C/EBP-homologous protein (CHOP) is a ubiquitously expressed stress-inducible transcription factor robustly induced by maladaptive endoplasmic reticulum (ER) stresses in a wide variety of cells. Here we examined a novel function of Sigma 1 receptor (Sigmar1) in regulating CHOP expression under ER-stress in cardiomyocytes. We also defined Sigmar1-dependent activation of the adaptive ER-stress pathway in regulating CHOP expression. We used adenovirus-mediated Sigmar1 overexpression as well as Sigmar1 knockdown by small interfering RNA (siRNA) in neonatal rat ventricular cardiomyocytes; to induce ER-stress cardiomyocytes were treated with tunicamycin...
June 30, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28666119/type-2-diabetes-variants-disrupt-function-of-slc16a11-through-two-distinct-mechanisms
#13
Victor Rusu, Eitan Hoch, Josep M Mercader, Danielle E Tenen, Melissa Gymrek, Christina R Hartigan, Michael DeRan, Marcin von Grotthuss, Pierre Fontanillas, Alexandra Spooner, Gaelen Guzman, Amy A Deik, Kerry A Pierce, Courtney Dennis, Clary B Clish, Steven A Carr, Bridget K Wagner, Monica Schenone, Maggie C Y Ng, Brian H Chen, Federico Centeno-Cruz, Carlos Zerrweck, Lorena Orozco, David M Altshuler, Stuart L Schreiber, Jose C Florez, Suzanne B R Jacobs, Eric S Lander
Type 2 diabetes (T2D) affects Latinos at twice the rate seen in populations of European descent. We recently identified a risk haplotype spanning SLC16A11 that explains ∼20% of the increased T2D prevalence in Mexico. Here, through genetic fine-mapping, we define a set of tightly linked variants likely to contain the causal allele(s). We show that variants on the T2D-associated haplotype have two distinct effects: (1) decreasing SLC16A11 expression in liver and (2) disrupting a key interaction with basigin, thereby reducing cell-surface localization...
June 29, 2017: Cell
https://www.readbyqxmd.com/read/28656874/cementless-femoral-components-in-bicondylar-hybrid-knee-arthroplasty-in-patients-with-rheumatoid-arthritis-a-10-year-survivorship-analysis
#14
Thilo Hotfiel, Hans-Dieter Carl, Teresa Eibenberger, Kolja Gelse, Julian Weiß, Andreas Jendrissek, Bernd Swoboda
BACKGROUND: Total knee arthroplasty (TKA) has been established as a successful surgical treatment in the late stages of rheumatoid joint destruction. The purpose of this study was to review the clinical outcome and survivorship in rheumatoid arthritis (RA) patients undergoing TKA in hybrid technique with a cementless fixation of the femoral component. METHODS: We analysed retrospectively 66 RA patients who underwent 72 TKAs (P.F.C. Sigma®). Mean follow-up time was 124 ± 41 months...
May 2017: Journal of Orthopaedic Surgery
https://www.readbyqxmd.com/read/28654186/haloperidol-decreases-hyperalgesia-and-allodynia-induced-by-chronic-constriction-injury
#15
Josué Vidal Espinosa-Juárez, Osmar Antonio Jaramillo-Morales, Francisco Javier López-Muñoz
Neuropathic pain has proven to be a difficult condition to treat, so investigational therapy has been sought that may prove useful, such as the use of sigma-1 antagonists. Haloperidol (HAL) is a compound that shows a high affinity with these receptors, acting as an antagonist. Therefore, the objective of this study was to demonstrate its effect in an experimental model of neuropathic pain and corroborate its antagonistic action of the sigma-1 receptors under these conditions. BD-1063 was used as a sigma-1 antagonist control and gabapentin was used as a positive control...
June 27, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28651382/assignment-of-sigma-factors-of-rna-polymerase-to-promoters-in-corynebacterium-glutamicum
#16
Hana Dostálová, Jiří Holátko, Tobias Busche, Lenka Rucká, Andrey Rapoport, Petr Halada, Jan Nešvera, Jörn Kalinowski, Miroslav Pátek
Corynebacterium glutamicum is an important industrial producer of various amino acids and other metabolites. The C. glutamicum genome encodes seven sigma subunits (factors) of RNA polymerase: the primary sigma factor SigA (σ(A)), the primary-like σ(B) and five alternative sigma factors (σ(C), σ(D), σ(E), σ(H) and σ(M)). We have developed in vitro and in vivo methods to assign particular sigma factors to individual promoters of different classes. In vitro transcription assays and measurements of promoter activity using the overexpression of a single sigma factor gene and the transcriptional fusion of the promoter to the gfpuv reporter gene enabled us to reliably define the sigma factor dependency of promoters...
December 2017: AMB Express
https://www.readbyqxmd.com/read/28648406/n-2-morpholin-4-yl-ethyl-2-1naphthyloxy-acetamide-inhibits-the-chronic-constriction-injury-generated-hyperalgesia-via-the-antagonism-of-sigma-1-receptors
#17
Josué Vidal Espinosa-Juárez, Osmar Antonio Jaramillo-Morales, Gabriel Navarrete-Vázquez, Luis Alberto Melo Hernández, Myrna Déciga-Campos, Francisco Javier López-Muñoz
The most used therapeutic treatment to relieve neuropathic pain is that of neuromodulators such as anti-epileptics or anti-depressants; however, there are alternatives that may be potentially useful. The sigma-1 receptor is a therapeutic target that has shown favorable results at preclinical levels. The aim of this study was to evaluate the anti-hyperalgesic effect of N-(2-morpholin-4-yl-ethyl)-2-(1-naphthyloxy) acetamide (NMIN) in a chronic constriction injury model (CCI) and compare it both a sigma-1 antagonist (BD-1063) and also Gabapentin, as well as determine its possible role as an antagonist of sigma-1 receptors...
June 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28644012/sigma-2-receptor-tmem97-agonists-produce-long-lasting-anti-neuropathic-pain-effects-in-mice
#18
James J Sahn, Galo L Mejia, Pradipta R Ray, Stephen F Martin, Theodore John Price
Neuropathic pain is an important medical problem with few effective treatments. The sigma 1 receptor (σ1R) is a potential target for neuropathic pain therapeutics, and antagonists for this receptor are effective in preclinical models and are currently in phase II clinical trials. Relatively little is known about the σ2R, which has recently been identified as transmembrane protein 97 (Tmem97). We generated a series of σ1R and σ2R/Tmem97 agonists and antagonists and tested them for efficacy in the mouse spared nerve injury (SNI) model...
June 23, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28643874/2-6-bis-diazaboryl-pyridine-a-superbasic-sterically-demanding-pyridine-ligand
#19
Tobias Böttcher, Daniel Himmel, Jan Schröder
Herein we present a convenient one-pot route to a sterically demanding superbasic pyridine. Functionalization of the 2,6-positions with the highly sigma-donating boryl-groups shifts the calculated gas phase basicity of the pyridine's nitrogen atom to 1012 kJ mol-1, which outperforms the 'proton sponge' 1,8-bis(dimethylamino)naphthalene (996 kJ mol-1). The diazaboryl groups are oriented orthogonal to the pyridine ring and do not block the N-position, resembling the geometry of commonly used N-heterocyclic carbenes...
June 23, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28643562/book-review-implementing-the-evidence-based-practice-ebp-competencies-in-healthcare-melnyk-b-gallagher-ford-l-fineout-overholt-e-implementing-the-evidence-based-practice-ebp-competencies-in-healthcare-indianapolis-in-sigma-theta-tau-international-honor-society
#20
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