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https://www.readbyqxmd.com/read/28443656/acyl-fluorides-fast-efficient-and-versatile-lysine-based-protein-conjugation-via-plug-and-play-strategy
#1
Igor Dovgan, Sylvain Ursuegui, Stéphane Erb, Chloé Michel, Sergii Kolodych, Sarah Cianférani, Alain Wagner
We report a plug-and-play strategy for the preparation of functionally enhanced antibodies with a defined average degree of conjugation (DoC). The first stage (plug) allows the controllable and efficient installation of azide groups on lysine residues of a native antibody using 4-azidobenzoyl fluoride. The second step (play) allows for versatile antibody functionalization with a single payload or combination of payloads, such as a toxin, a fluorophore, or an oligonucleotide, via copper-free strain-promoted azide-alkyne cycloaddition (SPAAC)...
April 26, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28433497/clostridium-difficile-toxin-glucosyltransferase-domains-in-complex-with-a-non-hydrolyzable-udp-glucose-analogue
#2
Joseph W Alvin, D Borden Lacy
Clostridium difficile is the leading cause of hospital-acquired diarrhea and pseudomembranous colitis worldwide. The organism produces two homologous toxins, TcdA and TcdB, which enter and disrupt host cell function by glucosylating and thereby inactivating key signalling molecules within the host. As a toxin-mediated disease, there has been a significant interest in identifying small molecule inhibitors of the toxins' glucosyltransferase activities. This study was initiated as part of an effort to identify the mode of inhibition for a small molecule inhibitor of glucosyltransferase activity called apigenin...
April 19, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/28431223/pink1-based-screen-shines-light-on-autophagy-enhancers-for-parkinson-s-disease
#3
Dominik Haddad, Ken Nakamura
In this issue of Cell Chemical Biology, Zhang et al. (2017) report a zebrafish model of Parkinson's disease (PD), incorporating the PD-protein PINK1 and rotenone, a toxin linked to PD. Using it as a drug-screening platform, they identify trifluoperazine and other piperazine phenothiazines as protective compounds that enhance autophagy independent of PINK1.
April 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28402338/insulin-deprivation-induces-pp2a-inhibition-and-tau-hyperphosphorylation-in-htau-mice-a-model-of-alzheimer-s-disease-like-tau-pathology
#4
Maud Gratuze, Jacinthe Julien, Franck R Petry, Françoise Morin, Emmanuel Planel
Abnormally hyperphosphorylated tau aggregated as intraneuronal neurofibrillary tangles is one of the two neuropathological hallmarks of Alzheimer's disease (AD). The majority of AD cases are sporadic with numerous environmental, biological and genetic risks factors. Interestingly, insulin dysfunction and hyperglycaemia are both risk factors for sporadic AD. However, how hyperglycaemia and insulin dysfunction affect tau pathology, is not well understood. In this study, we examined the effects of insulin deficiency on tau pathology in transgenic hTau mice by injecting different doses of streptozotocin (STZ), a toxin that destroys insulin-producing cells in the pancreas...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28385835/genome-sequence-of-a-toxin-positive-clostridium-difficile-strain-isolated-from-murine-feces
#5
Lucie Etienne-Mesmin, Benoit Chassaing, Oluwaseyi Adekunle, Lisa M Mattei, Adrianne N Edwards, Shonna M McBride, Frederic D Bushman, Andrew T Gewirtz
Herein, we report the genome sequence of a Clostridium difficile strain isolated from the feces of antibiotic-treated C57BL/6 mice. We have named this strain, which differs considerably from those of the previously sequenced C. difficile strains, LEM1.
April 6, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28382315/supervised-classification-of-etoposide-treated-in-vitro-adherent-cells-based-on-noninvasive-imaging-morphology
#6
Anna Leida Mölder, Johan Persson, Zahra El-Schich, Silvester Czanner, Anette Gjörloff-Wingren
Single-cell studies using noninvasive imaging is a challenging, yet appealing way to study cellular characteristics over extended periods of time, for instance to follow cell interactions and the behavior of different cell types within the same sample. In some cases, e.g., transplantation culturing, real-time cellular monitoring, stem cell studies, in vivo studies, and embryo growth studies, it is also crucial to keep the sample intact and invasive imaging using fluorophores or dyes is not an option. Computerized methods are needed to improve throughput of image-based analysis and for use with noninvasive microscopy such methods are poorly developed...
April 2017: Journal of Medical Imaging
https://www.readbyqxmd.com/read/28369668/selective-proteomic-proximity-labeling-assay-using-tyramide-spplat-a-quantitative-method-for-the-proteomic-analysis-of-localized-membrane-bound-protein-clusters
#7
Johanna Susan Rees, Xue-Wen Li, Sarah Perrett, Kathryn Susan Lilley, Antony Philip Jackson
This manuscript describes a new and general method to identify proteins localized into spatially restricted membrane microenvironments. Horseradish peroxidase (HRP) is brought into contact with a target protein by being covalently linked to a primary or secondary antibody, an antigen or substrate, a drug, or a toxin. A biotinylated tyramide-based reagent is then added. In the presence of HRP and hydrogen peroxide, the reagent is converted into a free radical that only diffuses a short distance before covalently labeling proteins within a few tens to hundreds of nanometers from the target...
April 3, 2017: Current Protocols in Protein Science
https://www.readbyqxmd.com/read/28357912/bioinformatic-prediction-and-experimental-validation-of-a-pe38-based-recombinant-immunotoxin-targeting-the-fn14-receptor-in-cancer-cells
#8
Maryam Keshtvarz, Jafar Salimian, Mehdi Yaseri, Seyedeh Zahra Bathaie, Ehsan Rezaie, Amir Aliramezani, Zahra Norouzbabaei, Jafar Amani, Masoumeh Douraghi
AIM: AFn14R can serve as an ideal target for cancer immunotherapy. Here, a combined bioinformatic and experimental approach was applied to characterize an immunotoxin consisting of single-chain variable fragment antibody that targets Fn14 and a toxin fragment (PE38). METHODS & RESULTS: Flow cytometry results showed that the rate of PE38-P4A8 binding to Fn14 was approximately 60 and 40% in HT-29 and A549 cells, respectively. Moreover, 1 ng/µl of immunotoxin was able to lyse approximately 53 and 41% of HT-29 and A549, respectively...
March 2017: Immunotherapy
https://www.readbyqxmd.com/read/28353450/predominance-of-clostridium-difficile-027-during-a-five-year-period-in-bolzano-northern-italy
#9
Richard Aschbacher, Alexander Indra, Christian J Wiedermann, Albert March, Bruno Giacon, Peter Mian, Mirella Bombonato, Angelika Kaneppele, Stefano Sansone, Johanna Burth, Alessandro Felici, Franziska Ebner, Werner Passler, Renelda M Lerchner, Claudio Vedovelli, Greta Spoladore, Raffaella Binazzi, Leonardo Pagani, Ludwig Moroder, Clara Larcher, Elisabetta Pagani
Toxigenic Clostridium difficile is responsible for antibiotic-associated diarrhoea and other diseases. The increasing frequency and severity is attributed to highly-virulent ribotypes such as 027. The aim of the study was to collect epidemiological and molecular data for C. difficile isolates during 2009-2013 in the Central Hospital of Bolzano, Northern Italy. Stool samples from inpatients of the Bolzano Central Hospital were screened for toxins A and B, and C. difficile was cultured and tested for antibiotic susceptibility...
March 1, 2017: Le Infezioni in Medicina
https://www.readbyqxmd.com/read/28334932/ribosome-dependent-vibrio-cholerae-mrnase-higb2-is-regulated-by-a-%C3%AE-strand-sliding-mechanism
#10
San Hadži, Abel Garcia-Pino, Sarah Haesaerts, Dukas Jurenas, Kenn Gerdes, Jurij Lah, Remy Loris
Toxin-antitoxin (TA) modules are small operons involved in bacterial stress response and persistence. higBA operons form a family of TA modules with an inverted gene organization and a toxin belonging to the RelE/ParE superfamily. Here, we present the crystal structures of chromosomally encoded Vibrio cholerae antitoxin (VcHigA2), toxin (VcHigB2) and their complex, which show significant differences in structure and mechanisms of function compared to the higBA module from plasmid Rts1, the defining member of the family...
February 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334216/deletion-of-mazf-increases-staphylococcus-aureus-biofilm-formation-in-an-ica-dependent-manner
#11
Fuminori Kato, Yusuke Yabuno, Yoshihiro Yamaguchi, Motoyuki Sugai, Masayori Inouye
Toxin-antitoxin (TA) systems are composed of a toxin that inhibits an essential cellular process (e.g., DNA replication, transcription, membrane integrity) and its cognate antitoxin that neutralizes the effect of the toxin. Staphylococcus aureus harbors two types of chromosomally encoded TA systems, namely mazEFsa encoding a UACAU-specific mRNA interferase and two paralogous genes of yefM-yoeBsa encoding a ribosome-dependent endoribonuclease system. However, little is known about the physiological role of MazEFsa and YefM-YoeBsa in S...
March 8, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28325299/potent-anti-seizure-effects-of-locked-nucleic-acid-antagomirs-targeting-mir-134-in-multiple-mouse-and-rat-models-of-epilepsy
#12
Cristina R Reschke, Luiz F Almeida Silva, Braxton A Norwood, Ketharini Senthilkumar, Gareth Morris, Amaya Sanz-Rodriguez, Ronán M Conroy, Lara Costard, Valentin Neubert, Sebastian Bauer, Michael A Farrell, Donncha F O'Brien, Norman Delanty, Stephanie Schorge, R Jeroen Pasterkamp, Felix Rosenow, David C Henshall
Current anti-epileptic drugs (AEDs) act on a limited set of neuronal targets, are ineffective in a third of patients with epilepsy, and do not show disease-modifying properties. MicroRNAs are small noncoding RNAs that regulate levels of proteins by post-transcriptional control of mRNA stability and translation. MicroRNA-134 is involved in controlling neuronal microstructure and brain excitability and previous studies showed that intracerebroventricular injections of locked nucleic acid (LNA), cholesterol-tagged antagomirs targeting microRNA-134 (Ant-134) reduced evoked and spontaneous seizures in mouse models of status epilepticus...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28324684/tea-is-a-key-virulence-factor-for-alternaria-alternata-fr-keissler-infection-of-its-host
#13
Ye Kang, Hongwei Feng, Jingxu Zhang, Shiguo Chen, Bernal E Valverde, Sheng Qiang
A toxin-deficient mutant strain, HP001 mutant of Alternaria alternata, whose mycelium is unable to infect its host, produces little tenuazonic acid (TeA) toxin. How TeA plays a role in initiating host infection by A. alternata remains unclear. In this research we use Imaging-PAM based on chlorophyll fluorescence parameters and transmission electron microscopy to explore the role of TeA toxin during the infection process of A. alternata. Photosystem II damage began even before wild type mycelium infected the leaves of its host, croftonweed (Ageratina adenophora)...
March 4, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28289514/modern-trends-in-animal-venom-research-omics-and-nanomaterials
#14
EDITORIAL
Yuri N Utkin
Animal venom research is a specialized investigation field, in which a number of different methods are used and this array is constantly expanding. Thus, recently emerged omics and nanotechnologies have already been successfully applied to venom research. Animal venoms have been studied for quite a long time. The traditional reductionist approach has been to isolate individual toxins and then study their structure and function. Unfortunately, the characterization of the venom as a whole system and its multiple effects on an entire organism were not possible until recent times...
February 26, 2017: World Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28282930/isolation-and-characterization-of-a-double-stranded-dna-megavirus-infecting-the-toxin-producing-haptophyte-prymnesium-parvum
#15
Ben A Wagstaff, Iulia C Vladu, J Elaine Barclay, Declan C Schroeder, Gill Malin, Robert A Field
Prymnesium parvum is a toxin-producing haptophyte that causes harmful algal blooms globally, leading to large-scale fish kills that have severe ecological and economic implications. For the model haptophyte, Emiliania huxleyi, it has been shown that large dsDNA viruses play an important role in regulating blooms and therefore biogeochemical cycling, but much less work has been done looking at viruses that infect P. parvum, or the role that these viruses may play in regulating harmful algal blooms. In this study, we report the isolation and characterization of a lytic nucleo-cytoplasmic large DNA virus (NCLDV) collected from the site of a harmful P...
March 9, 2017: Viruses
https://www.readbyqxmd.com/read/28270261/exploring-the-parameters-of-post-segregational-killing-using-heterologous-expression-of-secreted-toxin-barnase-and-antitoxin-barstar-in-an-escherichia-coli-case-study
#16
Dorien S Coray, Brigitta Kurenbach, Jack A Heinemann
Post-segregational killing (PSK) is a phenotype determined by plasmids using a toxin and an antitoxin gene pair. Loss of the genes depletes the cell's reserve of antitoxin and allows the toxin to act upon the cell. PSK benefits mobile elements when it increases reproductive success relative to other mobile competitors. A side effect of PSK is that plasmids become refractory to displacement from the cell during growth as a monoculture. Most PSK systems use a cytoplasmic toxin, but the external toxins of bacteriocins also have a PSK-like effect...
February 2017: Microbiology
https://www.readbyqxmd.com/read/28262508/the-role-of-ntcp-oatp2-bsep-and-mrp2-in-liver-injury-induced-by-dioscorea-bulbifera-l-and-diosbulbin-b-in-mice
#17
Xiao-Yu Qu, Li-Na Tao, Si-Xi Zhang, Jing-Meng Sun, Jun-Qi Niu, Yan-Hua Ding, Yan-Qing Song
Dioscorea bulbifera L. (DB) is a traditional Chinese herb used in thyroid disease and cancer. However, the clinical use of DB remains a challenge due to its hepatotoxicity, which is caused, in part, by the presence of Diosbulbin B (DIOB), a toxin commonly found in DB extracts. As abnormal expression of hepatobiliary transporters plays an important role in drug-induced liver injury, we assessed the hepatotoxicity induced by DB and DIOB, and explored their impacts on hepatobiliary transporter expression levels...
February 28, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28257063/red-yeast-rice
#18
Thu Nguyen, Mitchell Karl, Antonello Santini
Red yeast rice (RYR), produced by the fermentation of the Monascus purpureus mold, has been used for a long time in Asian cuisine and traditional medicine. It consists of multiple bioactive substances, including monacolins, which potentially can be used as a nutraceutical. Monacolin K, which is chemically identical to lovastatin, has been recognized as responsible for the cholesterolreducing effect of this compound. While the European Food Safety Authority maintains that the use of monacolin K from RYR preparations of at least 10 mg can produce a normal blood cholesterol level, the United States Food and Drug Administration considers monacolin K, due to its similarity with lovastatin, an unapproved drug, and therefore marketing of products that label the monacolin content is prohibited...
March 1, 2017: Foods (Basel, Switzerland)
https://www.readbyqxmd.com/read/28251677/mitochondrial-dna-and-primary-mitochondrial-dysfunction-in-parkinson-s-disease
#19
REVIEW
Maria Pia Giannoccaro, Chiara La Morgia, Giovanni Rizzo, Valerio Carelli
In 1979, it was observed that parkinsonism could be induced by a toxin inhibiting mitochondrial respiratory complex I. This initiated the long-standing hypothesis that mitochondrial dysfunction may play a key role in the pathogenesis of Parkinson's disease (PD). This hypothesis evolved, with accumulating evidence pointing to complex I dysfunction, which could be caused by environmental or genetic factors. Attention was focused on the mitochondrial DNA, considering the occurrence of mutations, polymorphic haplogroup-specific variants, and defective mitochondrial DNA maintenance with the accumulation of multiple deletions and a reduction of copy number...
March 2, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28241077/%C3%AE-amanitin-resistance-in-drosophila-melanogaster-a-genome-wide-association-approach
#20
Chelsea L Mitchell, Catrina E Latuszek, Kara R Vogel, Ian M Greenlund, Rebecca E Hobmeier, Olivia K Ingram, Shannon R Dufek, Jared L Pecore, Felicia R Nip, Zachary J Johnson, Xiaohui Ji, Hairong Wei, Oliver Gailing, Thomas Werner
We investigated the mechanisms of mushroom toxin resistance in the Drosophila Genetic Reference Panel (DGRP) fly lines, using genome-wide association studies (GWAS). While Drosophila melanogaster avoids mushrooms in nature, some lines are surprisingly resistant to α-amanitin-a toxin found solely in mushrooms. This resistance may represent a pre-adaptation, which might enable this species to invade the mushroom niche in the future. Although our previous microarray study had strongly suggested that pesticide-metabolizing detoxification genes confer α-amanitin resistance in a Taiwanese D...
2017: PloS One
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