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https://www.readbyqxmd.com/read/29123973/cholera-toxin-b-subunit-induces-local-curvature-on-lipid-bilayers
#1
Weria Pezeshkian, Lina J Nåbo, John H Ipsen
The B subunit of the bacterial cholera toxin (CTxB) is responsible for the toxin binding to the cell membrane and its intracellular trafficking. CTxB binds to the monosialotetrahexosyl ganglioside at the plasma membrane of the target cell and mediates toxin internalization by endocytosis. CTxB induces a local membrane curvature that is essential for its clathrin-independent uptake. Using all-atom molecular dynamics, we show that CTxB induces local curvature, with the radius of curvature around 36 nm. The main feature of the CTxB molecular structure that causes membrane bending is the protruding alpha helices in the middle of the protein...
November 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/29111771/staphylococcus-aureus-alpha-toxin-induces-actin-filament-remodeling-in-human-airway-epithelial-model-cells
#2
Sabine Ziesemer, Ina Eiffler, Alfrun Schönberg, Christian Müller, Falko Hochgräfe, Achim G Beule, Jan-Peter Hildebrandt
Exposure of cultured human airway epithelial model cells (16HBE14o-, S9) to Staphylococcus aureus alpha-toxin (hemolysin A, Hla) induces changes in cell morphology and cell layer integrity which are due to the inability of the cells to maintain stable cell-cell or focal contacts and to properly organize their actin cytoskeleton. The aim of this study was to identify Hla-activated signaling pathways involved in regulating the phosphorylation level of the actin depolymerizing factor cofilin. We used recombinant wild-type Hla (rHla) as well as a variant of Hla (rHla-H35L) that is unable to form functional transmembrane pores to treat immortalized human airway epithelial cells (16HBE14o-, S9) as well as freshly isolated human nasal tissue...
November 7, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29102330/oral-vaccination-of-broiler-chickens-against-necrotic-enteritis-using-a-non-virulent-netb-positive-strain-of-clostridium-perfringens-type-a
#3
Neha Mishra, Joan A Smyth
Necrotic enteritis (NE) is a severe disease of chickens and turkeys caused by some strains of Clostridium perfringens type A. The disease is well controlled by the use of in-feed antibiotic growth promoters (AGPs). However, due to worldwide public and regulatory pressure to reduce the use of AGPs inter alia, there is an urgent need to develop non-antibiotic based preventative measures. Vaccination would be a suitable control measure, but currently there is no commercial vaccine. NetB (necrotic enteritis toxin B-like) is a pore-forming toxin produced by C...
November 1, 2017: Vaccine
https://www.readbyqxmd.com/read/29100712/-quercetin-attenuates-staphylococcus-aureus-virulence-by-reducing-alpha-toxin-secretion
#4
Gabriela Carrada López, Carlos A Castañón Sánchez
Alpha toxin, a pore-forming protein with cytotoxic activity, is one of the major virulence factors secreted by most strains of Staphylococcus aureus. The relevance of this protein in the pathogenesis of pneumonia associated with S.aureus infections has already been established. Therefore, inhibiting alpha toxin secretion can be an alternative for controlling these infections. This study shows that quercetin, a naturally occurring flavonoid, inhibits hemolytic activity in a dose-dependent manner and reduces alpha toxin secretion in culture supernatants of methicillin-sensitive and methicillin-resistant S...
October 31, 2017: Revista Argentina de Microbiología
https://www.readbyqxmd.com/read/29099326/disarming-staphylococcus-aureus-from-destroying-human-cells-by-simultaneously-neutralizing-six-cytotoxins-with-two-human-monoclonal-antibodies
#5
Harald Rouha, Susanne Weber, Philipp Janesch, Barbara Maierhofer, Karin Gross, Ivana Dolezilkova, Irina Mirkina, Zehra C Visram, Stefan Malafa, Lukas Stulik, Adriana Badarau, Eszter Nagy
Pathogenesis of Staphylococcus aureus is increasingly recognized to be driven by powerful toxins. Staphylococcus aureus employs up to six pore-forming toxins to subvert the human host defense and to promote bacterial invasion: alpha-hemolysin that disrupts epithelial and endothelial barriers and five leukocidins that lyse phagocytes involved in bacterial clearance. Previously, we described two human monoclonal antibodies (mAbs), ASN-1 that neutralizes alpha-hemolysin and four leukocidins (LukSF-PV, LukED, HlgAB, HlgCB), and ASN-2 that inactivates the 5(th) leukocidin, LukGH...
November 3, 2017: Virulence
https://www.readbyqxmd.com/read/29046869/staphylococcus-aureus-alpha-toxin-induces-the-formation-of-dynamic-tubules-labeled-with-lc3-within-host-cells-in-a-rab7-and-rab1b-dependent-manner
#6
María M López de Armentia, María C Gauron, María I Colombo
Staphylococcus aureus is a pathogen that causes severe infectious diseases that eventually lead to septic and toxic shock. S. aureus infection is characterized by the production of virulence factors, including enzymes and toxins. After internalization S. aureus resides in a phagosome labeled with Rab7 protein. Here, we show that S. aureus generates tubular structures marked with the small GTPases Rab1b and Rab7 and by the autophagic protein LC3 at early times post-infection. As shown by live cell imaging these tubular structures are highly dynamic, extend, branch and grow in length...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29034215/the-proteome-of-biologically-active-membrane-vesicles-from-piscirickettsia-salmonis-lf-89-type-strain-identifies-plasmid-encoded-putative-toxins
#7
Cristian Oliver, Mauricio A Hernández, Julia I Tandberg, Karla N Valenzuela, Leidy X Lagos, Ronie E Haro, Patricio Sánchez, Pamela A Ruiz, Constanza Sanhueza-Oyarzún, Marcos A Cortés, María T Villar, Antonio Artigues, Hanne C Winther-Larsen, Ruben Avendaño-Herrera, Alejandro J Yáñez
Piscirickettsia salmonis is the predominant bacterial pathogen affecting the Chilean salmonid industry. This bacterium is the etiological agent of piscirickettsiosis, a significant fish disease. Membrane vesicles (MVs) released by P. salmonis deliver several virulence factors to host cells. To improve on existing knowledge for the pathogenicity-associated functions of P. salmonis MVs, we studied the proteome of purified MVs from the P. salmonis LF-89 type strain using multidimensional protein identification technology...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29030011/influence-of-pasteurella-multocida-toxin-on-the-differentiation-of-dendritic-cells-into-osteoclasts
#8
Sushmita Chakraborty, Bianca Kloos, Nina Roetz, Silke Schmidt, Tatjana Eigenbrod, Shigeki Kamitani, Katharina F Kubatzky
Dendritic cells (DC) are antigen-presenting cells that connect the innate and adaptive immune system to ensure an efficient immune response during the course of an infection. Recently, DC came into the spotlight as a potential source of osteoclast progenitors, especially under (auto)inflammatory conditions. The virulence factor Pasteurella multocida Toxin (PMT) causes atrophic rhinitis in pigs, a disease characterised by a severe reduction of nasal bone. Our group and others have shown the potential of PMT in mediating differentiation of monocytes/macrophages into bone-resorbing osteoclasts...
September 12, 2017: Immunobiology
https://www.readbyqxmd.com/read/29018619/alpha-arylphorin-is-a-mitogen-in-the-heliothis-virescens-midgut-cell-secretome-upon-cry1ac-intoxication
#9
Anais Castagnola, Jerreme Jackson, Omaththage P Perera, Cris Oppert, Shigetoshi Eda, Juan Luis Jurat-Fuentes
Insecticidal crystal (Cry) proteins produced by the bacterium Bacillus thuringiensis (Bt) target cells in the midgut epithelium of susceptible larvae. While the mode of action of Cry toxins has been extensively investigated, the midgut response to Cry intoxication and its regulation are not well characterized. In this work, we describe the secreted proteome (secretome) of primary mature midgut cell cultures from Heliothis virescens larvae after exposure to Cry1Ac toxin compared to control buffer treatment. The Cry1Ac-induced secretome caused higher proliferation and differentiation and an overall reduction in total cell mortality over time in primary H...
2017: PeerJ
https://www.readbyqxmd.com/read/28988777/delta-toxin-from-clostridium-perfringens-perturbs-intestinal-epithelial-barrier-function-in-caco-2-cell-monolayers
#10
Soshi Seike, Masaya Takehara, Teruhisa Takagishi, Kazuaki Miyamoto, Keiko Kobayashi, Masahiro Nagahama
Clostridium perfringens delta-toxin is a β-barrel-pore-forming toxin (β-PFT) and a presumptive virulence factor of type B and C strains, which are causative organisms of fatal intestinal diseases in animals. We showed previously that delta-toxin causes cytotoxicity via necrosis in sensitive cells. Here, we examined the effect of delta-toxin on intestinal membrane integrity. Delta-toxin led to a reduction in transepithelial electrical resistance (TEER) and increased the permeability of fluorescence isothiocyanate-conjugated dextran in human intestinal epithelial Caco-2 cells without changing the tight junction proteins, such as zonula occludens-1 (ZO-1), occludin, and claudin-1...
October 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28987047/-epidemiology-and-risk-factors-of-hepatocellular-carcinoma
#11
REVIEW
Agnieszka Budny, Piotr Kozłowski, Marzena Kamińska, Małgorzata Jankiewicz, Agnieszka Kolak, Bożena Budny, Witold Budny, Joanna Niemunis-Sawicka, Grzegorz Szczypiór, Bartosz Kurniawka, Franciszek Burdan
Primary liver neoplasms occurs relatively rarely in Poland. The most frequently occurring type of cancer is hepatocellular carcinoma (HCC), which globally constitutes 7% of all the occurrences of cancer. The incidence increases with age and is the highest in patients around the age of 70. It also varies significantly depending on the geographic location. The main factors that cause HCC are infection of HBV and HCV, whose genome integrates into the DNA of the host, causing mutations. The other factors include excessive alcohol consumption, contact or consumption of Aspergillus toxins as well as various metabolic disorders, such as α1-antitrypsin deficiency, hemochromatosis, tyrosinemia, porphyria, von Gierke disease and in person with gene mutation p...
September 29, 2017: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28958733/identification-of-bacillus-thuringiensis-cry1abmod-binding-proteins-from-spodoptera-frugiperda
#12
Diana L Martínez de Castro, Blanca I García-Gómez, Isabel Gómez, Alejandra Bravo, Mario Soberón
Bacillus thuringiensis Cry toxins are currently used for pest control in transgenic crops but evolution of resistance by the insect pests threatens the use of this technology. The Cry1AbMod toxin was engineered to lack the alpha helix-1 of the parental Cry1Ab toxin and was shown to counter resistance to Cry1Ab and Cry1Ac toxins in different insect species including the fall armyworm Spodoptera frugiperda. In addition, Cry1AbMod showed enhanced toxicity to Cry1Ab-susceptible S. frugiperda populations. To gain insights into the mechanisms of this Cry1AbMod-enhanced toxicity, we isolated the Cry1AbMod toxin binding proteins from S...
September 25, 2017: Peptides
https://www.readbyqxmd.com/read/28953886/non-homeostatic-body-weight-regulation-through-a-brainstem-restricted-receptor-for-gdf15
#13
Jer-Yuan Hsu, Suzanne Crawley, Michael Chen, Dina A Ayupova, Darrin A Lindhout, Jared Higbee, Alan Kutach, William Joo, Zhengyu Gao, Diana Fu, Carmen To, Kalyani Mondal, Betty Li, Avantika Kekatpure, Marilyn Wang, Teresa Laird, Geoffrey Horner, Jackie Chan, Michele McEntee, Manuel Lopez, Damodharan Lakshminarasimhan, Andre White, Sheng-Ping Wang, Jun Yao, Junming Yie, Hugo Matern, Mark Solloway, Raj Haldankar, Thomas Parsons, Jie Tang, Wenyan D Shen, Yu Alice Chen, Hui Tian, Bernard B Allan
Under homeostatic conditions, animals use well-defined hypothalamic neural circuits to help maintain stable body weight, by integrating metabolic and hormonal signals from the periphery to balance food consumption and energy expenditure. In stressed or disease conditions, however, animals use alternative neuronal pathways to adapt to the metabolic challenges of altered energy demand. Recent studies have identified brain areas outside the hypothalamus that are activated under these 'non-homeostatic' conditions, but the molecular nature of the peripheral signals and brain-localized receptors that activate these circuits remains elusive...
October 12, 2017: Nature
https://www.readbyqxmd.com/read/28930551/uremic-toxins-are-conditional-danger-or-homeostasis-associated-molecular-patterns
#14
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
#15
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 18, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28919674/prevalence-of-enteropathogens-and-their-antibiotic-sensitivity-pattern-in-puppies-with-hemorrhagic-gastroenteritis
#16
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
#17
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
#18
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
#19
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
#20
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
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