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https://www.readbyqxmd.com/read/29327957/unusual-outbreak-of-fatal-clostridiosis-in-a-group-of-captive-brown-pelicans-pelecanus-occidentalis
#1
Imke Lueders, Carsten Ludwig, Johanna Kasberg, Christoph Georg Baums, Kerstin Klimke, Martin B Dorner, Dana Ströse, Volker Schmidt
Fatal clostridial infections and clostridial toxicoses are common in birds. Most fatalities are associated with toxin production and progress rapidly, often within 24 hours of infection. We describe an unusual and protracted course of disease in 6 captive brown pelicans ( Pelecanus occidentalis), which was believed to result from toxicosis by toxovar A produced by a mixed infection with Clostridium sordellii and Clostridium perfringens. Although the first death in the group occurred 3 days after signs of illness were documented, the remaining birds died over a 38-day period despite aggressive antibiotic and supportive therapy...
December 2017: Journal of Avian Medicine and Surgery
https://www.readbyqxmd.com/read/29320451/the-pathogenesis-of-staphylococcus-aureus-eye-infections
#2
REVIEW
Richard J O'Callaghan
Staphylococcus aureus is a major pathogen of the eye able to infect the tear duct, eyelid, conjunctiva, cornea, anterior and posterior chambers, and the vitreous chamber. Of these infections, those involving the cornea (keratitis) or the inner chambers of the eye (endophthalmitis) are the most threatening because of their potential to cause a loss in visual acuity or even blindness. Each of these ocular sites is protected by the constitutive expression of a variety of antimicrobial factors and these defenses are augmented by a protective host response to the organism...
January 10, 2018: Pathogens
https://www.readbyqxmd.com/read/29304344/endogenous-reprogramming-of-alpha-cells-into-beta-cells-induced-by-viral-gene-therapy-reverses-autoimmune-diabetes
#3
Xiangwei Xiao, Ping Guo, Chiyo Shiota, Ting Zhang, Gina M Coudriet, Shane Fischbach, Krishna Prasadan, Joseph Fusco, Sabarinathan Ramachandran, Piotr Witkowski, Jon D Piganelli, George K Gittes
Successful strategies for treating type 1 diabetes need to restore the function of pancreatic beta cells that are destroyed by the immune system and overcome further destruction of insulin-producing cells. Here, we infused adeno-associated virus carrying Pdx1 and MafA expression cassettes through the pancreatic duct to reprogram alpha cells into functional beta cells and normalized blood glucose in both beta cell-toxin-induced diabetic mice and in autoimmune non-obese diabetic (NOD) mice. The euglycemia in toxin-induced diabetic mice and new insulin+ cells persisted in the autoimmune NOD mice for 4 months prior to reestablishment of autoimmune diabetes...
January 4, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29295977/staphylococcus-aureus-produces-pain-through-pore-forming-toxins-and-neuronal-trpv1-that-is-silenced-by-qx-314
#4
Kimbria J Blake, Pankaj Baral, Tiphaine Voisin, Ashira Lubkin, Felipe Almeida Pinho-Ribeiro, Kelsey L Adams, David P Roberson, Yuxin C Ma, Michael Otto, Clifford J Woolf, Victor J Torres, Isaac M Chiu
The hallmark of many bacterial infections is pain. The underlying mechanisms of pain during live pathogen invasion are not well understood. Here, we elucidate key molecular mechanisms of pain produced during live methicillin-resistant Staphylococcus aureus (MRSA) infection. We show that spontaneous pain is dependent on the virulence determinant agr and bacterial pore-forming toxins (PFTs). The cation channel, TRPV1, mediated heat hyperalgesia as a distinct pain modality. Three classes of PFTs-alpha-hemolysin (Hla), phenol-soluble modulins (PSMs), and the leukocidin HlgAB-directly induced neuronal firing and produced spontaneous pain...
January 2, 2018: Nature Communications
https://www.readbyqxmd.com/read/29287670/investigation-of-clostridium-botulinum-group-iii-s-mobilome-content
#5
Cédric Woudstra, Caroline Le Maréchal, Rozenn Souillard, Fabrizio Anniballi, Bruna Auricchio, Luca Bano, Marie-Hélène Bayon-Auboyer, Miriam Koene, Isabelle Mermoud, Roseane B Brito, Francisco C F Lobato, Rodrigo O S Silva, Martin B Dorner, Patrick Fach
Clostridium botulinum group III is mainly responsible for botulism in animals. It could lead to high animal mortality rates and, therefore, represents a major environmental and economic concern. Strains of this group harbor the botulinum toxin locus on an unstable bacteriophage. Since the release of the first complete C. botulinum group III genome sequence (strain BKT015925), strains have been found to contain others mobile elements encoding for toxin components. In this study, seven assays targeting toxin genes present on the genetic mobile elements of C...
December 26, 2017: Anaerobe
https://www.readbyqxmd.com/read/29278784/elucidating-the-biogeographical-variation-of-the-venom-of-naja-naja-spectacled-cobra-from-pakistan-through-a-venom-decomplexing-proteomic-study
#6
Kin Ying Wong, Choo Hock Tan, Kae Yi Tan, Quraishi H Naeem, Nget Hong Tan
Naja naja is a medically important species that is distributed widely in South Asia. Its venom lethality and neutralization profile have been reported to vary markedly, but the understanding of this phenomenon has been limited without a comprehensive venom profile for the Pakistani N. naja. This study set to investigate the venom proteome of Pakistani N. naja applying reverse-phase HPLC, SDS-PAGE, mass spectrometry and data-mining approaches. The venom enzymatics and antigen binding activities were also studied...
December 23, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/29277539/skin-wound-healing-is-accelerated-by-a-lipid-mixture-representing-major-lipid-components-of-chamaecyparis-obtusa-plant-extract
#7
Byung Eui Kim, Elena Goleva, Clifton F Hall, Sang Hyun Park, Un Ha Lee, Anne M Brauweiler, Joanne E Streib, Brittany N Richers, Gwuicheol Kim, Donald Y M Leung
In chronic non-healing wounds, the healing process is disrupted and wounds are often infected with bacteria. About 85% of lower extremity amputations in diabetes are attributed to deep infection of foot ulcers. Therefore, infection control is critical for wound care. In this study, we analyzed lipid composition of Chamaecyparis (C) obtusa extract, and describe the wound healing properties of its combination of ten major lipid components. A 10 lipid mixture upregulated HBD-3 and LL-37 through the olfactory receptor 2AT4, and induced phosphorylation of extracellular signal-regulated kinases and p38 mitogen-activated protein kinases in primary human keratinocytes...
December 22, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29273510/epigallocatechin-gallate-can-attenuate-human-alveolar-epithelial-cell-injury-induced-by-alpha-haemolysin
#8
Yonglin Zhou, Chengzhen Chen, Juan Pan, Xuming Deng, Jianfeng Wang
Staphylococcus aureus (S. aureus) is a common cause of hospital-acquired infection and has become an epidemic globally. Alpha-haemolysin (α-haemolysin), a pore-forming toxin, is one of the most important virulence factors secreted by most S. aureus strains. α-haemolysin monomers form a 232.4-kDa membrane-inserted heptamer by self-assembling to cause host cell lysis and death. Consequently, α-haemolysin plays a significant role in the pathogenesis of S. aureus, and it could be the target for the treatment of staphylococcal infection...
December 19, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29246841/immunization-with-a-nontoxic-naturally-occurring-clostridium-perfringens-alpha-toxin-induces-neutralizing-antibodies-in-rabbits
#9
Flávia de Faria Siqueira, Rodrigo Otávio Silveira Silva, Anderson Oliveira do Carmo, Bárbara Bruna Ribeiro de Oliveira Mendes, Carolina Campolina Rebello Horta, Francisco Carlos Faria Lobato, Evanguedes Kalapothakis
Clostridium perfringens alpha toxin, encoded by plc gene, has been implicated in gas gangrene, a life threatening infection. Vaccination is considered one of the best solutions against Clostridium infections. Although studies have identified many low quality clostridial vaccines, the use of recombinant proteins has been considered a promising alternative. Previously, a naturally occurring alpha toxin isoform (αAV1b) was identified with a mutation at residue 11 (His/Tyr), which can affect its enzymatic activity...
December 12, 2017: Anaerobe
https://www.readbyqxmd.com/read/29228930/gene-expression-analysis-in-asthma-using-a-targeted-multiplex-array
#10
Christopher D Pascoe, Ma'en Obeidat, Bryna A Arsenault, Yunlong Nie, Stephanie Warner, Dorota Stefanowicz, Samuel J Wadsworth, Jeremy A Hirota, S Jasemine Yang, Delbert R Dorscheid, Chris Carlsten, Tillie L Hackett, Chun Y Seow, Peter D Paré
BACKGROUND: Gene expression changes in the structural cells of the airways are thought to play a role in the development of asthma and airway hyperresponsiveness. This includes changes to smooth muscle contractile machinery and epithelial barrier integrity genes. We used a targeted gene expression arrays to identify changes in the expression and co-expression of genes important in asthma pathology. METHODS: RNA was isolated from the airways of donor lungs from 12 patients with asthma (8 fatal) and 12 non-asthmatics controls and analyzed using a multiplexed, hypothesis-directed platform to detect differences in gene expression...
December 11, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/29228352/tumour-necrosis-factor-alpha-in-uraemic-serum-promotes-osteoblastic-transition-and-calcification-of-vascular-smooth-muscle-cells-via-extracellular-signal-regulated-kinases-and-activator-protein-1-c-fos-mediated-induction-of-interleukin-6-expression
#11
Daniel Zickler, Christian Luecht, Kevin Willy, Lei Chen, Janusz Witowski, Matthias Girndt, Roman Fiedler, Markus Storr, Julian Kamhieh-Milz, Janosch Schoon, Sven Geissler, Olle Ringdén, Ralf Schindler, Guido Moll, Duska Dragun, Rusan Catar
Background: Vascular calcification is enhanced in uraemic chronic haemodialysis patients, likely due to the accumulation of midsize uraemic toxins, such as interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Here we have assessed the impact of uraemia on vascular smooth muscle cell (VSMC) calcification and examined the role of IL-6 and TNF-α as possible mediators and, most importantly, its underlying signalling pathway in VSMCs. Methods: VSMCs were incubated with samples of uraemic serum obtained from patients treated with haemodialysis for renal failure in the Permeability Enhancement to Reduce Chronic Inflammation-I clinical trial...
December 8, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29224513/infectious-necrotic-hepatitis-caused-by-clostridium-novyi-type-b-in-a-horse-case-report-and-review-of-the-literature
#12
Akinyi C Nyaoke, Mauricio A Navarro, Juliann Beingesser, Francisco A Uzal
A 14-y-old bay Quarter Horse gelding was presented with progressive neurologic signs, elevated rectal temperature, and icterus for 3 d prior to death. Postmortem examination revealed icterus, large amounts of serosanguineous fluid in the abdominal cavity, widespread petechiae and ecchymoses in several organs, and a large, pale, and well-demarcated focus of necrosis in the liver. Histologically, there was coagulative necrosis surrounded by a rim of inflammatory cells and large numbers of gram-positive rods, which were identified as Clostridium novyi by immunohistochemistry...
December 1, 2017: Journal of Veterinary Diagnostic Investigation
https://www.readbyqxmd.com/read/29216804/the-use-of-alpha-fetoprotein-for-the-treatment-of-autoimmune-diseases-and-cancer
#13
Vladimir N Pak
Alpha-fetoprotein is a shuttle protein that delivers nutrients through receptor-mediated endocytosis to embryotic cells. In adults, alpha-fetoprotein can shuttle drugs into alpha-fetoprotein receptor-positive myeloid-derived suppressor, regenerating and also cancer cells. Drugs with high-binding affinity to alpha-fetoprotein can activate or deplete targeted cells. Myeloid-derived suppressor cells activation leads to immune suppression that can be used for treating autoimmune diseases. On the other hand, toxins delivered by alpha-fetoprotein can damage myeloid-derived suppressor cells and consequently unleash innate and adaptive immunity to destroy cancer cells...
January 2018: Therapeutic Delivery
https://www.readbyqxmd.com/read/29216295/alpha-1-antichymotrypsin-is-involved-in-astrocyte-injury-in-concert-with-arginine-vasopressin-during-the-development-of-acute-hepatic-encephalopathy
#14
Jonghyuk Park, Takahiro Masaki, Yoshihiro Mezaki, Hiroshi Yokoyama, Mariko Nakamura, Haruka Maehashi, Takahiko J Fujimi, Sabine S Gouraud, Keisuke Nagatsuma, Madoka Nakagomi, Naofumi Kimura, Tomokazu Matsuura
BACKGROUND AND AIMS: We developed a bio-artificial liver (BAL) using a radial-flow bioreactor and rescued mini-pig models with lethal acute liver failure (ALF). The point of the rescue is the recovery from hepatic encephalopathy (HE). HE on ALF has sometimes resulted in brain death following brain edema with astrocyte swelling. Several factors, including ammonia and glutamine, have been reported to induce astrocyte swelling and injury. However, many clinicians believe that there are any other factors involved in the development of HE...
2017: PloS One
https://www.readbyqxmd.com/read/29216246/draft-genome-sequence-of-actinotignum-schaalii-dsm-15541t-genetic-insights-into-the-lifestyle-cell-fitness-and-virulence
#15
Atteyet F Yassin, Stefan Langenberg, Marcel Huntemann, Alicia Clum, Manoj Pillay, Krishnaveni Palaniappan, Neha Varghese, Natalia Mikhailova, Supratim Mukherjee, T B K Reddy, Chris Daum, Nicole Shapiro, Natalia Ivanova, Tanja Woyke, Nikos C Kyrpides
The permanent draft genome sequence of Actinotignum schaalii DSM 15541T is presented. The annotated genome includes 2,130,987 bp, with 1777 protein-coding and 58 rRNA-coding genes. Genome sequence analysis revealed absence of genes encoding for: components of the PTS systems, enzymes of the TCA cycle, glyoxylate shunt and gluconeogensis. Genomic data revealed that A. schaalii is able to oxidize carbohydrates via glycolysis, the nonoxidative pentose phosphate and the Entner-Doudoroff pathways. Besides, the genome harbors genes encoding for enzymes involved in the conversion of pyruvate to lactate, acetate and ethanol, which are found to be the end products of carbohydrate fermentation...
2017: PloS One
https://www.readbyqxmd.com/read/29197248/the-role-of-il-8-cxcr2-signaling-in-microcystin-lr-triggered-endothelial-cell-activation-and-increased-vascular-permeability
#16
Limei Chen, Xiaoying Liu, Zhifang Pan, Shunmei Liu, Huirong Han, Chunling Zhao, Xuexi Tang
Microcystins are a family of cyclic heptapeptide toxins naturally produced by freshwater cyanobacteria. Microcystin-LR (MCLR) is believed to be the most toxic and common one with various pathological effects on human and mammals. However, the effects of MCLR on endothelial cells and vascular homeostasis have been largely unknown. We explored the mRNA and protein expression changes of several pro-inflammatory mediators in human umbilical vein endothelial cells (HUVECs) and C57BC/6 mice exposed to MCLR. Tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), especially interleukin-8 (IL-8) were remarkably upregulated both in endothelial cells and in serum...
November 25, 2017: Chemosphere
https://www.readbyqxmd.com/read/29175591/linking-t-cell-epitopes-to-a-common-linear-b-cell-epitope-a-targeting-and-adjuvant-strategy-to-improve-t-cell-responses
#17
Sara M Mangsbo, Erika A K Fletcher, Wendy W C van Maren, Anke Redeker, Robert A Cordfunke, Inken Dillmann, Jasper Dinkelaar, Kahina Ouchaou, Jeroen D C Codee, Gijs A van der Marel, Peter Hoogerhout, Cornelis J M Melief, Ferry Ossendorp, Jan W Drijfhout
Immune complexes are potent mediators of cellular immunity and have been extensively studied for their disease mediating properties in humans and for their role in anti-cancer immunity. However, a viable approach to use antibody-complexed antigen as vehicle for specific immunotherapy has not yet reached clinical use. Since virtually all people have endogenous antibodies against tetanus toxoid (TTd), such commonly occurring antibodies are promising candidates to utilize for immune modulation. As an initial proof-of-concept we investigated if anti-tetanus IgG could induce potent cross-presentation of a conjugate with SIINFEKL, a MHC class I presented epitope of ovalbumin (OVA), to TTd...
November 22, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29123973/cholera-toxin-b-subunit-induces-local-curvature-on-lipid-bilayers
#18
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
#19
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
#20
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
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