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https://www.readbyqxmd.com/read/28930551/uremic-toxins-are-conditional-danger-or-homeostasis-associated-molecular-patterns
#1
Yu Sun, Candice Johnson, Jun Zhou, Luqiao Wang, Ya-Feng Li, Yifan Lu, Gayani Nanayakkara, Hangfei Fu, Ying Shao, Claudette Sanchez, William Y Yang, Xin Wang, Eric T Choi, Rongshan Li, Hong Wang, Xiao-Feng Yang
We mined novel uremic toxin (UT) metabolomics/gene databases, and analyzed the expression changes of UT receptors and UT synthases in chronic kidney disease (CKD) and cardiovascular disease (CVD). We made the following observations: 1) UTs represent only 1/80(th) of human serum small-molecule metabolome; 2) Some UTs are increased in CKD and CVD; 3) UTs either induce or suppress the expression of inflammatory molecules; 4) The expression of UT genes is significantly modulated in CKD patients, and coronary artery disease (CAD) patients; 5) The expression of UT genes is upregulated by caspase-1 and TNF-alpha pathways but is inhibited in regulatory T cells...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28923495/crispr-cas9-engineering-of-adult-mouse-liver-demonstrates-that-the-dnajb1-prkaca-gene-fusion-is-sufficient-to-induce-tumors-resembling-fibrolamellar-hepatocellular-carcinoma
#2
Lars H Engelholm, Anjum Riaz, Denise Serra, Frederik Dagnæs-Hansen, Jens V Johansen, Eric Santoni-Rugiu, Steen H Hansen, Francesco Niola, Morten Frödin
BACKGROUND & AIMS: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a primary liver cancer that predominantly affects young adults with no underlying liver disease. A somatic, 400 Kb deletion on chromosome 19 that fuses part of the DnaJ heat shock protein family (Hsp40) member B1 gene (DNAJB1) to the protein kinase cAMP-activated catalytic subunit alpha gene (PRKACA) has been repeatedly identified in patients with FL-HCC. However, the DNAJB1-PRKACA gene fusion has not been shown to induce liver tumorigenesis...
September 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28919674/prevalence-of-enteropathogens-and-their-antibiotic-sensitivity-pattern-in-puppies-with-hemorrhagic-gastroenteritis
#3
A Kokila Priya, M Balagangatharathilagar, D Chandrasekaran, M Parthiban, S Prathaban
AIM: Hemorrhagic gastroenteritis (HGE) ranging from mild to severe forms is commonly encountered in puppies. The aim of the study was to identify the prevalence of common enteropathogens and the antibiotic sensitivity pattern in puppies reported with HGE. MATERIALS AND METHODS: The canine HGE activity index, with little modification, was adopted to identify Grade III/severely affected puppies below 6 months of age. Fecal polymerase chain reaction (PCR) assay was employed to screen and compare the enteropathogens in puppies with hemorrhagic diarrhea and healthy control...
August 2017: Veterinary World
https://www.readbyqxmd.com/read/28910576/impact-of-staphylococcus-aureus-regulatory-mutations-that-modulate-biofilm-formation-in-the-usa300-strain-lac-on-virulence-in-a-murine-bacteremia-model
#4
Joseph S Rom, Danielle N Atwood, Karen E Beenken, Daniel G Meeker, Allister J Loughran, Horace J Spencer, Tamara L Lantz, Mark S Smeltzer
Staphylococcus aureus causes acute and chronic forms of infection, the latter often associated with formation of a biofilm. It has previously been demonstrated that mutation of atl, codY, rot, sarA, and sigB limits biofilm formation in the USA300 strain LAC while mutation of agr, fur, and mgrA has the opposite effect. Here we used a murine sepsis model to assess the impact of these same loci in acute infection. Mutation of agr, atl, and fur had no impact on virulence, while mutation of mgrA and rot increased virulence...
September 14, 2017: Virulence
https://www.readbyqxmd.com/read/28857644/recombinant-scorpion-toxins-focus-on-four-disulfide-peptide-blockers-of-kv1-channels
#5
Oksana Nekrasova, Sergey Yakimov, Mikhail Kirpichnikov, Alexey Feofanov
We have recently developed a simple and effective bioengineering approach to large-scale production of alpha-KTx, peptide toxins from scorpion venoms, that block voltage-gated potassium channels with high affinity and specificity. This approach was successfully approved for different peptides containing three disulfide bonds. To extend this method to production of peptide toxins with four disulfide bridges, in particular, maurotoxin and hetlaxin, appropriate conditions of a cleavage reaction with tobacco etch virus (TEV) protease need to be found...
August 31, 2017: Bioengineered
https://www.readbyqxmd.com/read/28807495/the-colorful-spectrum-of-tourette-syndrome-and-its-medical-surgical-and-behavioral-therapies
#6
Jan Roth
Tourette syndrome (TS) is a common neuropsychiatric disorder, more common in males than females, with onset before age 18. TS is characterized by multiple motor tics and one or more vocal/phonic tics, persisting for more than a year. Tics are unvoluntary, abrupt, rapid, repetitive, but non-rhythmic movements or sounds (vocalizations). They are preceded by an inner urge. Tics can be temporarily suppressed, but this leads to a powerful re-emergence. The performance of tics results in immediate but transient relief...
August 10, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28783084/enter-the-dragon-the-dynamic-and-multifunctional-evolution-of-anguimorpha-lizard-venoms
#7
Ivan Koludarov, Timothy Nw Jackson, Bianca Op den Brouw, James Dobson, Daniel Dashevsky, Kevin Arbuckle, Christofer J Clemente, Edward J Stockdale, Chip Cochran, Jordan Debono, Carson Stephens, Nadya Panagides, Bin Li, Mary-Louise Roy Manchadi, Aude Violette, Rudy Fourmy, Iwan Hendrikx, Amanda Nouwens, Judith Clements, Paolo Martelli, Hang Fai Kwok, Bryan G Fry
While snake venoms have been the subject of intense study, comparatively little work has been done on lizard venoms. In this study, we have examined the structural and functional diversification of anguimorph lizard venoms and associated toxins, and related these results to dentition and predatory ecology. Venom composition was shown to be highly variable across the 20 species of Heloderma, Lanthanotus, and Varanus included in our study. While kallikrein enzymes were ubiquitous, they were also a particularly multifunctional toxin type, with differential activities on enzyme substrates and also ability to degrade alpha or beta chains of fibrinogen that reflects structural variability...
August 6, 2017: Toxins
https://www.readbyqxmd.com/read/28775097/platelet-derived-growth-factor-receptor-alpha-pdgfr%C3%AE-and-ras-related-c3-botulinum-toxin-substrate-1-rac1-regulate-mechano-responsiveness-of-lung-fibroblasts
#8
Stephen E McGowan, Diann M McCoy
Platelet-derived growth factor (PDGF)-A, which only signals through PDGF-receptor-alpha (PDGFRα) is required for secondary alveolar septal formation. Although PDGFRα distinguishes mesenchymal progenitor cells during the saccular stage, PDGFRα-expressing alveolar cells persist through adulthood. PDGF-A sustains proliferation, limits apoptosis, and maintains alpha-smooth muscle actin (αSMA) containing alveolar cells, which congregate at the alveolar entry ring at postnatal day (P)12. PDGFRα-expressing, αSMA-containing, alveolar cells re-distribute in the elongating septum, suggesting that they migrate to the alveolar entry rings where mechanical tension is higher...
August 3, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28718163/incidence-and-management-of-lower-urinary-tract-symptoms-after-urethral-stricture-repair
#9
REVIEW
Amanda S J Chung, Kurt A McCammon
Lower urinary tract symptoms (LUTS) after urethral stricture repair are not uncommon. Urgency has been reported in 40% of men and urge incontinence in 12% of men after anterior urethroplasty. De novo urgency and urge incontinence is seen in 9 and 5% of men, respectively, after urethroplasty. Once a complication of urethroplasty (such as recurrent urethral stricture or diverticulum) has been excluded as a cause, evaluation of LUTS in such patients should focus on differentiating bladder dysfunction (overactive bladder, underactive bladder), from other outlet obstruction (such as benign prostatic obstruction), dysfunctional voiding, or medical causes (such as nocturnal polyuria)...
September 2017: Current Urology Reports
https://www.readbyqxmd.com/read/28688806/evaluation-of-the-genotoxicity-of-alpha-amanitin-in-mice-bone-marrow-cells
#10
B Marciniak, D Łopaczyńska, T Ferenc
Alpha-amanitin is a known cytotoxic substance found in some mushroom species including Amanita phalloides. Its main mechanism of action is to block the transcription, which can lead to cell death. Lack of reports on the genotoxicity of this toxin was an inspiration for undertaking this experiment. Genotoxic effect of α-amanitin on balb/c mice bone marrow cells was tested using: comet assay and chromosomal aberration test. The tested substance was given once by intraperitoneal administration to animals at doses: 0...
July 6, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28685236/engineered-cry1ac-cry9aa-hybrid-bacillus-thuringiensis-delta-endotoxin-with-improved-insecticidal-activity-against-helicoverpa-armigera
#11
Jigar V Shah, Rakeshkumar Yadav, Sanjay S Ingle
Recombinant Bt construct was prepared by exchange of pore forming domain I with cry1Ac to cry9Aa gene by overlap extension PCR (OE-PCR) technique. Construction of cry1Ac-cry9Aa was accomplished by six base pair homology at 3' ends of PCR products of domain I of cry1Ac and domain II and III of cry9Aa. The recombinant toxin was also modified by deletion of N-terminal alpha helix-1 of recombinant toxin. Both Cry toxins were expressed in E. coli BL21(DE3) plysS and purified by His-tag purification. Upon insect bioassay analysis against devastating crop pest Helicoverpa armigera, toxicity of recombinant toxin was found around fivefold higher than native Cry1Ac while alpha helix-1 deleted N-terminal modified toxin did not resulted in significant increase in toxicity...
July 6, 2017: Archives of Microbiology
https://www.readbyqxmd.com/read/28683345/interaction-of-acylated-and-unacylated-forms-of-e-coli-alpha-hemolysin-with-lipid-monolayers-a-pm-irras-study
#12
Romina F Vázquez, María A Daza Millone, Felippe J Pavinatto, Vanesa S Herlax, Laura S Bakás, Osvaldo N Oliveira, María E Vela, Sabina M Maté
Uropathogenic strains of Escherichia coli produce virulence factors, such as the protein toxin alpha-hemolysin (HlyA), that enable the bacteria to colonize the host and establish an infection. HlyA is synthetized as a protoxin (ProHlyA) that is transformed into the active form in the bacterial cytosol by the covalent linkage of two fatty-acyl moieties to the polypeptide chain before the secretion of HlyA into the extracellular medium. The aim of this work was to investigate the effect of the fatty acylation of HlyA on protein conformation and protein-membrane interactions...
June 24, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28672859/astrocytic-expression-of-gsta4-is-associated-to-dopaminergic-neuroprotection-in-a-rat-6-ohda-model-of-parkinson-s-disease
#13
Michael Jewett, Itzia Jimenez-Ferrer, Maria Swanberg
Idiopathic Parkinson's disease (PD) is a complex disease caused by multiple, mainly unknown, genetic and environmental factors. The Ventral root avulsion 1 (Vra1) locus on rat chromosome 8 includes the Glutathione S-transferase alpha 4 (Gsta4) gene and has been identified in crosses between Dark Agouti (DA) and Piebald Virol Glaxo (PVG) rat strains as being associated to neurodegeneration after nerve and brain injury. The Gsta4 protein clears lipid peroxidation by-products, a process suggested to being implicated in PD...
June 26, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28665720/characterization-of-clostridium-perfringens-strains-isolated-from-healthy-and-necrotic-enteritis-afflicted-broiler-chickens
#14
Charles Li, Hyun S Lillehoj, Ujvala Deepthi Gadde, Don Ritter, SungTaek Oh
Necrotic enteritis (NE) is an important enteric disease in poultry, and Clostridium perfringens (CP) type A strains are the primary etiology. NE is responsible for annual losses of US $6 billion to the poultry industry in the United States. An increase in the incidence of NE has been also associated with withdrawal of antibiotic growth promoters from poultry feed. In this study, CP strains isolated from healthy and NE-afflicted birds were characterized microbiologically and molecularly, and their virulence was experimentally tested in chickens...
June 2017: Avian Diseases
https://www.readbyqxmd.com/read/28660750/urinary-manifestations-in-isaacs-s-syndrome-our-experience-in-8-cases
#15
Silvia N Gonzalez Primomo, Leandro Blas, Alicia C Bertotti, Carlos Ameri
INTRODUCTION: Isaacs's syndrome (IS), is a rare neurological disorder, characterized by sustained muscular activity, fasciculations, cramps, myokymia, excessive sweating, and occasional elevation of creatine phosphokinase (CPK) enzyme. AIM: To report our experience in patients with IS and urinary manifestations, describing clinical findings, test's results, and response to treatment. Methods An observational, retrospective analysis of patients with IS and urinary manifestations treated at German Hospital of Buenos Aires between 2001 and 2011 was done...
June 29, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28660200/a-fast-and-inexpensive-protocol-for-empirical-verification-of-neutralizing-epitopes-in-microbial-toxins-and-enzymes
#16
Christine N Vuong, Wen-Ko Chou, Vivek A Kuttappan, Billy M Hargis, Lisa R Bielke, Luc R Berghman
In vivo targeting of peptides to antigen-presenting cells by use of agonistic anti-CD40 monoclonal antibodies has been used successfully as an immune response enhancing strategy. When tested in chickens, the antibody-guided platform was capable of inducing specific IgG production within 1 week postimmunization. However, use of this method beyond its initial conception as a vaccine delivery tool has not been fully exploited. In this study, Clostridium perfringens alpha-toxin was used as a model microbial toxin for epitope mapping by using the antibody-guided immunization method to generate a panel of antibodies against specific, regions of the toxin in an attempt to identify crucial determinants on the toxin which, once bound, would hinder downstream toxicity...
2017: Frontiers in Veterinary Science
https://www.readbyqxmd.com/read/28659169/the-novel-compound-pbt434-prevents-iron-mediated-neurodegeneration-and-alpha-synuclein-toxicity-in-multiple-models-of-parkinson-s-disease
#17
David I Finkelstein, Jessica L Billings, Paul A Adlard, Scott Ayton, Amelia Sedjahtera, Colin L Masters, Simon Wilkins, David M Shackleford, Susan A Charman, Wojciech Bal, Izabela A Zawisza, Ewa Kurowska, Andrew L Gundlach, Sheri Ma, Ashley I Bush, Dominic J Hare, Philip A Doble, Simon Crawford, Elisabeth Cl Gautier, Jack Parsons, Penny Huggins, Kevin J Barnham, Robert A Cherny
Elevated iron in the SNpc may play a key role in Parkinson's disease (PD) neurodegeneration since drug candidates with high iron affinity rescue PD animal models, and one candidate, deferirpone, has shown efficacy recently in a phase two clinical trial. However, strong iron chelators may perturb essential iron metabolism, and it is not yet known whether the damage associated with iron is mediated by a tightly bound (eg ferritin) or lower-affinity, labile, iron pool. Here we report the preclinical characterization of PBT434, a novel quinazolinone compound bearing a moderate affinity metal-binding motif, which is in development for Parkinsonian conditions...
June 28, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28652930/a-simple-electroelution-method-for-rapid-protein-purification-isolation-and-antibody-production-of-alpha-toxin-from-clostridium-septicum
#18
Lorena Vázquez-Iglesias, Borja Estefanell-Ucha, Leticia Barcia-Castro, María Páez de la Cadena, Paula Álvarez-Chaver, Daniel Ayude-Vázquez, Francisco Javier Rodríguez-Berrocal
Clostridium septicum produces a number of diseases in human and farm animals which, in most of the cases, are fatal without clinical intervention. Alpha toxin is an important agent and the unique lethal virulent factor produced by Clostridium septicum. This toxin is haemolytic, highly lethal and necrotizing activities but is being used as an antigen to develop animal vaccines. The aim of this study was to isolate the alpha toxin of Clostridium septicum and produce highly specific antibodies against it. In this work, we have developed a simple and efficient method for alpha toxin purification, based on electroelution that can be used as a time-saving method for purifying proteins...
2017: PeerJ
https://www.readbyqxmd.com/read/28565773/pien-tze-huang-gan-bao-ameliorates-carbon-tetrachloride-induced-hepatic-injury-oxidative-stress-and-inflammation-in-rats
#19
Jinyan Zhao, Haixia Hu, Yun Wan, Yuchen Zhang, Liangpu Zheng, Zhenfeng Hong
Liver damage results from a variety of insults, including hepatitis and chemical toxicity from alcohol, drugs and other toxins. The present study evaluated the hepatoprotective effects and potential mechanisms of action of the Traditional Chinese Medicine Pien Tze Huang Gan Bao (GB) in a rat model of carbon tetrachloride (CCl4)-induced liver injury. Sixty male Sprague-Dawley rats were randomly divided into six different groups: i) Control, ii) CCl4 injury model and groups treated with iii) silymarin as a positive drug control, iv) 150 mg/kg GB, v) 300 mg/kg GB and vi) 600 mg/kg GB...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28484480/single-event-resolution-of-plant-plasma-membrane-protein-endocytosis-by-tirf-microscopy
#20
Alexander Johnson, Grégory Vert
Endocytosis is a key process in the internalization of extracellular materials and plasma membrane proteins, such as receptors and transporters, thereby controlling many aspects of cell signaling and cellular homeostasis. Endocytosis in plants has an essential role not only for basic cellular functions but also for growth and development, nutrient delivery, toxin avoidance, and pathogen defense. The precise mechanisms of endocytosis in plants remain quite elusive. The lack of direct visualization and examination of single events of endocytosis has greatly hampered our ability to precisely monitor the cell surface lifetime and the recruitment profile of proteins driving endocytosis or endocytosed cargos in plants...
2017: Frontiers in Plant Science
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