scholarly journals New class of precision antimicrobials redefines role of Clostridium difficile S-layer in virulence and viability

2017 ◽  
Vol 9 (406) ◽  
pp. eaah6813 ◽  
Author(s):  
Joseph A. Kirk ◽  
Dana Gebhart ◽  
Anthony M. Buckley ◽  
Stephen Lok ◽  
Dean Scholl ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
New Class

Practical consensus recommendations - Current role of immune response evaluation criteria in solid tumors criteria in the management of cancer patients receiving immunotherapy

2019 ◽  
Vol 4 ◽  
pp. 21-23
Author(s):  
Purvish M. Parikh ◽  
T. P. Sahoo ◽  
Randeep Singh ◽  
Bahl Ankur ◽  
Talvar Vineet ◽  
...  
Keyword(s):  
Immune Response ◽  
Solid Tumors ◽  
Evaluation Criteria ◽  
Supporting Evidence ◽  
Response Evaluation ◽  
Consensus Recommendation ◽  
Current Role ◽  
New Class ◽  
Response Evaluation Criteria

Response evaluation criteria in solid tumors (RECIST) are a method used to evaluate and document the response to cancer treatment in solid tumors. The availability of a new class of immuneoncology drugs has resulted in the need to modify RECIST criteria methodology. The first leadership immuno-oncology network (LION) master course brought together experts in oncology and immuno-oncology. Six questions were put to the experts and their opinion, supporting evidence, and experience were discussed to arrive at a practical consensus recommendation. n this nascent field, the availability of a practical consensus recommendation developed by experts in the field is of immense value to the community oncologist and other health-care consultants.

scholarly journals Recent Advances in Fabrication of Non-Isocyanate Polyurethane-Based Composite Materials

Materials ◽  
2021 ◽  
Vol 14 (13) ◽  
pp. 3497
Author(s):  
Piotr Stachak ◽  
Izabela Łukaszewska ◽  
Edyta Hebda ◽  
Krzysztof Pielichowski
Keyword(s):  
Raw Materials ◽  
Synthesis Method ◽  
Polymeric Materials ◽  
Original Research ◽  
Significant Group ◽  
Oh Groups ◽  
New Class ◽  
Hazardous Chemical ◽  
Wide Range

Polyurethanes (PUs) are a significant group of polymeric materials that, due to their outstanding mechanical, chemical, and physical properties, are used in a wide range of applications. Conventionally, PUs are obtained in polyaddition reactions between diisocyanates and polyols. Due to the toxicity of isocyanate raw materials and their synthesis method utilizing phosgene, new cleaner synthetic routes for polyurethanes without using isocyanates have attracted increasing attention in recent years. Among different attempts to replace the conventional process, polyaddition of cyclic carbonates (CCs) and polyfunctional amines seems to be the most promising way to obtain non-isocyanate polyurethanes (NIPUs) or, more precisely, polyhydroxyurethanes (PHUs), while primary and secondary –OH groups are being formed alongside urethane linkages. Such an approach eliminates hazardous chemical compounds from the synthesis and leads to the fabrication of polymeric materials with unique and tunable properties. The main advantages include better chemical, mechanical, and thermal resistance, and the process itself is invulnerable to moisture, which is an essential technological feature. NIPUs can be modified via copolymerization or used as matrices to fabricate polymer composites with different additives, similar to their conventional counterparts. Hence, non-isocyanate polyurethanes are a new class of environmentally friendly polymeric materials. Many papers on the matter above have been published, including both original research and extensive reviews. However, they do not provide collected information on NIPU composites fabrication and processing. Hence, this review describes the latest progress in non-isocyanate polyurethane synthesis, modification, and finally processing. While focusing primarily on the carbonate/amine route, methods of obtaining NIPU are described, and their properties are presented. Ways of incorporating various compounds into NIPU matrices are characterized by the role of PHU materials in copolymeric materials or as an additive. Finally, diverse processing methods of non-isocyanate polyurethanes are presented, including electrospinning or 3D printing.

Agronomic, breeding, and biotechnological approaches to parasitic plant management through manipulation of germination stimulant levels in agricultural soils

Botany ◽  
2011 ◽  
Vol 89 (12) ◽  
pp. 813-826 ◽  
Author(s):  
M. Fernández-Aparicio ◽  
J.H. Westwood ◽  
D. Rubiales
Keyword(s):  
Mycorrhizal Fungi ◽  
Agricultural Soils ◽  
Host Recognition ◽  
Plant Management ◽  
Parasitic Weed ◽  
Germination Stimulant ◽  
New Class ◽  
Agronomic Practices ◽  
Number Of Plant Species

A number of plant species have adapted to parasitize other plants, and some parasitic species pose severe constraints to major crops. The role of strigolactones and other metabolites present in host root exudates as germination stimulants for weedy root parasitic weed seeds has been known for the last 40 years. Recently, the ecological and developmental roles of strigolactones have been clarified by the discovery that they are a new class of plant hormone that controls shoot branching and serve as host recognition signals for mycorrhizal fungi. Parasitic plants also recognize these chemicals and use them to coordinate their life cycle with that of their host. Here we review agronomic practices that use parasitic germination stimulant production as a target for manipulation to control parasitic weeds.

scholarly journals Genetic and Phenotypic Analyses of therdx Locus of Rhodobacter sphaeroides2.4.1

2000 ◽  
Vol 182 (12) ◽  
pp. 3475-3481 ◽  
Author(s):  
Jung Hyeob Roh ◽  
Samuel Kaplan
Keyword(s):  
Gene Expression ◽  
Rhodobacter Sphaeroides ◽  
Redox Protein ◽  
Deletion Mutations ◽  
Metal Transporter ◽  
New Class ◽  
Mutant Strains ◽  
Membrane Bound ◽  
Photosynthesis Gene

ABSTRACT Previously, we reported that rdxB, encoding a likely membrane-bound two [4Fe-4S]-containing center, is involved in the aerobic regulation of photosystem gene expression in Rhodobacter sphaeroides 2.4.1. To further investigate the role ofrdxB as well as other genes of the rdxBHISoperon on photosystem gene expression, we constructed a series of nonpolar, in-frame deletion mutations in each of the rdxgenes. Using both puc and puf operonlacZ fusions to monitor photosystem gene expression, under aerobic conditions, in each of the mutant strains revealed significant increased photosynthesis gene expression. In the case of mutations in either rdxH, rdxI, or rdxS, the aerobic induction of photosystem gene expression is believed to be indirect by virtue of a posttranscriptional effect oncbb 3 cytochrome oxidase structure and integrity. For RdxB, we suggest that this redox protein has a more direct effect on photosystem gene expression by virtue of its interaction with the cbb 3 oxidase. An associated phenotype, involving the enhanced conversion of the carotenoid spheroidene to spheroidenone, is also observed in the RdxB, -H, -I, and -S mutant strains. This phenotype is also suggested to be the result of the role of the rdxBHIS locus incbb 3 oxidase activity and/or structure. RdxI is suggested to be a new class of metal transporter of the CPx-type ATPases.

scholarly journals Phenotypic Susceptibility to Bevirimat in Isolates from HIV-1-Infected Patients without Prior Exposure to Bevirimat

2010 ◽  
Vol 54 (6) ◽  
pp. 2345-2353 ◽  
Author(s):  
Nicolas A. Margot ◽  
Craig S. Gibbs ◽  
Michael D. Miller
Keyword(s):  
Recombinant Viruses ◽  
Gag Polyprotein ◽  
New Class ◽  
Major Mutation ◽  
Hiv Drugs ◽  
The Impact ◽  
First Time ◽  
Hiv 1

ABSTRACT Bevirimat (BVM) is the first of a new class of anti-HIV drugs with a novel mode of action known as maturation inhibitors. BVM inhibits the last cleavage of the Gag polyprotein by HIV-1 protease, leading to the accumulation of the p25 capsid-small peptide 1 (SP1) intermediate and resulting in noninfectious HIV-1 virions. Early clinical studies of BVM showed that over 50% of the patients treated with BVM did not respond to treatment. We investigated the impact of prior antiretroviral (ARV) treatment and/or natural genetic diversity on BVM susceptibility by conducting in vitro phenotypic analyses of viruses made from patient samples. We generated 31 recombinant viruses containing the entire gag and protease genes from 31 plasma samples from HIV-1-infected patients with (n = 21) or without (n = 10) prior ARV experience. We found that 58% of the patient isolates tested had a >10-fold reduced susceptibility to BVM, regardless of the patient's ARV experience or the level of isolate resistance to protease inhibitors. Analysis of mutants with site-directed mutations confirmed the role of the V370A SP1 polymorphism (SP1-V7A) in resistance to BVM. Furthermore, we demonstrated for the first time that a capsid polymorphism, V362I (CA protein-V230I), is also a major mutation conferring resistance to BVM. In contrast, none of the previously defined resistance-conferring mutations in Gag selected in vitro (H358Y, L363M, L363F, A364V, A366V, or A366T) were found to occur among the viruses that we analyzed. Our results should be helpful in the design of diagnostics for prediction of the potential benefit of BVM treatment in HIV-1-infected patients.

Exploring Structural Dynamics and Optical Properties of UnaG Fluorescent Protein upon N57 Mutations

2021 ◽  
Author(s):  
Mohammad Asad ◽  
Adèle D Laurent
Keyword(s):  
Optical Properties ◽  
Structural Dynamics ◽  
Fluorescent Protein ◽  
Green Light ◽  
Endogenous Ligand ◽  
New Class ◽  
Fluorescence Protein

UnaG is a new class of fluorescence protein for which an endogenous ligand namely bilirubin (BLR) is playing the role of the chromophore. Upon photoexcitation, holoUnaG emits the green light....

scholarly journals Cyclic Diguanylate Regulates Virulence Factor Genes via Multiple Riboswitches inClostridium difficile

mSphere ◽  
2018 ◽  
Vol 3 (5) ◽  
Author(s):  
Robert W. McKee ◽  
Carissa K. Harvest ◽  
Rita Tamayo
Keyword(s):  
Gene Expression ◽  
Clostridium Difficile ◽  
Biofilm Formation ◽  
Toxin Production ◽  
Intestinal Colonization ◽  
Cyclic Diguanylate ◽  
Signaling Molecule ◽  
Content Type ◽  
Surface Motility

ABSTRACTThe intracellular signaling molecule cyclic diguanylate (c-di-GMP) regulates many processes in bacteria, with a central role in controlling the switch between motile and nonmotile lifestyles. Recent work has shown that inClostridium difficile(also calledClostridioides difficile), c-di-GMP regulates swimming and surface motility, biofilm formation, toxin production, and intestinal colonization. In this study, we determined the transcriptional regulon of c-di-GMP inC. difficile,employing overexpression of a diguanylate cyclase gene to artificially manipulate intracellular c-di-GMP. Consistent with prior work, c-di-GMP regulated the expression of genes involved in swimming and surface motility. c-di-GMP also affected the expression of multiple genes encoding cell envelope proteins, several of which affected biofilm formationin vitro. A substantial proportion of the c-di-GMP regulon appears to be controlled either directly or indirectly via riboswitches. We confirmed the functionality of 11 c-di-GMP riboswitches, demonstrating their effects on downstream gene expression independent of the upstream promoters. The class I riboswitches uniformly functioned as “off” switches in response to c-di-GMP, while class II riboswitches acted as “on” switches. Transcriptional analyses of genes 3′ of c-di-GMP riboswitches over a broad range of c-di-GMP levels showed that relatively modest changes in c-di-GMP levels are capable of altering gene transcription, with concomitant effects on microbial behavior. This work expands the known c-di-GMP signaling network inC. difficileand emphasizes the role of the riboswitches in controlling known and putative virulence factors inC. difficile.IMPORTANCEInClostridium difficile, the signaling molecule c-di-GMP regulates multiple processes affecting its ability to cause disease, including swimming and surface motility, biofilm formation, toxin production, and intestinal colonization. In this study, we used RNA-seq to define the transcriptional regulon of c-di-GMP inC. difficile. Many new targets of c-di-GMP regulation were identified, including multiple putative colonization factors. Transcriptional analyses revealed a prominent role for riboswitches in c-di-GMP signaling. Only a subset of the 16 previously predicted c-di-GMP riboswitches were functionalin vivoand displayed potential variability in their response kinetics to c-di-GMP. This work underscores the importance of studying c-di-GMP riboswitches in a relevant biological context and highlights the role of the riboswitches in controlling gene expression inC. difficile.

scholarly journals 187 Emerging Role of Fecal Microbiota Therapy in the Treatment of Recurrent Clostridium difficile Infection in Children

2013 ◽  
Vol 144 (5) ◽  
pp. S-45
Author(s):  
Shashank Garg ◽  
W.F. Fricke ◽  
Mohit Girotra ◽  
Erik C. von Rosenvinge ◽  
Anand Dutta ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Clostridium Difficile Infection ◽  
Fecal Microbiota ◽  
Recurrent Clostridium Difficile Infection

Understanding the Mechanisms of Efficacy of Fecal Microbiota Transplantation in the Treatment of Clostridium Difficile Infection: The Potential Role of Bilemetabolising Enzymes

2017 ◽  
Vol 152 (5) ◽  
pp. S47 ◽  
Author(s):  
Benjamin H. Mullish ◽  
Julie A. McDonald ◽  
Dina H. Kao ◽  
Jessica R. Allegretti ◽  
Elaine O. Petrof ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Clostridium Difficile Infection ◽  
Potential Role ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota
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