197 research outputs found
Proline-Rich Peptides with Improved Antimicrobial Activity against E. coli, K. Pneumoniae, and A. Baumannii.
No full textProline-rich antimicrobial peptides (PrAMPs) are promising agents to combat multi-drug resistant pathogens due to a high antimicrobial activity, yet low cytotoxicity. A library of derivatives of the PrAMP Bac5(1-17) was synthesized and screened to identify which residues are relevant for its activity. In this way, we discovered that two central motifs -PIRXP- cannot be modified, while residues at N- and C- termini tolerated some variations. We found five Bac5(1-17) derivatives bearing 1-5 substitutions, with an increased number of arginine and/or tryptophan residues, exhibiting improved antimicrobial activity and broader spectrum of activity while retaining low cytotoxicity toward eukaryotic cells. Transcription/translation and bacterial membrane permeabilization assays showed that these new derivatives still retained the ability to strongly inhibit bacterial protein synthesis, but also acquired permeabilizing activity to different degrees. These new Bac5(1-17) derivatives therefore show a dual mode of action which could hinder the selection of bacterial resistance against these molecules
Peptide inhibitors of bacterial protein synthesis with broad spectrum and SbmA-independent bactericidal activity against clinical pathogens.
No full textProline-rich antimicrobial peptides (PrAMPs) are promising lead compounds for developing new antimicrobials, however their narrow spectrum of action is limiting. PrAMPs kill bacteria binding to their ribosomes and inhibiting protein synthesis. In this study, 133 derivatives of the PrAMP Bac7(1-16) were synthesized to identify the crucial residues for ribosome inactivation and antimicrobial activity. Then, five new Bac7(1-16) derivatives were conceived and characterized by antibacterial and membrane permeabilization assays, by X-ray crystallography and molecular dynamics simulations. Some derivatives displayed broad spectrum activity, encompassing Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa and Staphylococcus aureus. Two peptides out of five, acquired a weak membrane-perturbing activity, while maintaining the ability to inhibit protein synthesis. These derivatives became independent of the SbmA transporter, commonly used by native PrAMPs, suggesting that they obtained a novel route to enter bacterial cells. PrAMP-derived compounds could become new-generation antimicrobials to combat the antibiotic-resistant pathogens
When Do Children Dislike Ingroup Members? Resource Allocation from Individual and Group Perspectives
No full textDo children like ingroup members who challenge group norms about resource allocation? Further, do children evaluate from their own individual perspective? Participants (N = 381), aged 9.5 and 13.5 years, evaluated members of their own group who deviated from group norms about resource allocation by either: (1) advocating for equal allocation in contrast to the group norm of inequality; or (2) advocating for inequality when the group norm was to divide equally. With age, participants differentiated their own individual favorability from the group's favorability of deviant members of the ingroup. Further, when deciding between group loyalty and equal allocation, children and adolescents gave priority to equality, rejecting group decisions to dislike ingroup members who advocated for equality
Bibliographics for the 983 eprints in the live archives of E-LIS : trends and status report up to 7th July 2004, based on author-self-archiving metadata
No full textThe priority for ideas and philosophy related to "Network Theory" have been traced back and documented by Braun(2004),and credit goes to Karinthy(1929).The IT has empowered to realise it, as the most practical phenomena and it is no more a humour. The OAI (Open Archives Initiatives)and ACIS (Academic Contributor Information System)are progressive in the direction ,which may lead to realise the "Collective Genius" at global level. Focus of present study is on Author-Self-Archiving (A-S-A)Metadata of the 983 Eprints in the Live Archives of the E-LIS (EPrints of Library and Information Science),which were approved till 7th July 2004.The A-S-A Metadata was used for librametric analysis. Self-explanatory bibliographics are illustrated.The highlights include: Conference papers (34%); highest approval, June 2004 (28%); published archives (76%);not refereed (52%); not in public domain (60%); highest self-archiving-author (De Robbio, Antonella).The Nos. of EPrints having single JITA domain specifications were: Theoretical and general aspects of libraries and information(27); Information use and sociology of information(80);Users,literacy and reading(13);Libraries as physical collections(30);Publishing and legal issues(57);Management(13);Industry, profession and education(36);Information sources, supports, channels(113) ; Information treatment for information services, Information functions and techniques (101); Technical services libraries, archives and museums(25); Housing technologies(1); Information technology and library technology(92); and Inter-domainery (395) i.e. having specifications of two or more than two JITA classes
Author Correction: Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways
No full textCorrection to: Nature Communicationshttps://doi.org/10.1038/s41467-024-48422-x, published online 15 May 2024 The original version of this Article omitted from the author list the 28th author Rozanne Arulanandam, who is from the ‘Ottawa Hospital Research Insitute, Ottawa, ON, K1H 8L6, Canada’. Consequently, the following was added to the Author Contributions: ‘R.A. performed the revision experiments on cell lines shown in Figures 1 and 2, in particular, the virus titration and GFP measurements of virus infection in CT26wt and 76-9 with 4OI.’ The original version of this Article omitted funding details to R.L. The following was added to the Acknowledgements: ‘This research was supported by grants to R.L. from the Canadian Institutes of Health Research (CIHR) (PJT-169663).’ These have been corrected in both the PDF and HTML versions of the Article.<p/
The effect of lipidation and glycosylation on short cationic antimicrobial peptides
No full textThe global health threat surrounding bacterial resistance has resulted in antibiotic researchers shifting their focus away from ‘traditional’ antibiotics and concentrating on other antimicrobial agents, including antimicrobial peptides. These low molecular weight "mini-proteins" exhibit broad-spectrum activity against bacteria, including multi-drug resistant strains, viruses, fungi and protozoa and constitute a major element of the innate-immune system of many multicellular organisms. Some naturally occurring antimicrobial peptides are lipidated and/or glycosylated and almost all antimicrobial peptides in clinical use are either lipopeptides (Daptomycin and Polymyxin E and B) or glycopeptides (Vancomycin). Lipidation, glycosylation and PEGylation are an option for improving stability and activity in serum and for reducing the rapid clearing via the kidneys and liver. Two broad-spectrum antimicrobial peptides NH2-RIRIRWIIR-CONH2 (A1) and NH2-KRRVRWIIW-CONH2 (B1) were conjugated via a linker, producing A2 and B2, to individual fatty acids of C8, C10, C12 and C14 and in addition, A2 was conjugated to either glucose, N-acetyl glucosamine, galactose, mannose, lactose or polyethylene glycol (PEG). Antimicrobial activity against two Gram-positive strains (methicillin resistant Staphylococcus aureus (MRSA) and vancomycin resistant Enterococcus faecalis (VRE)) and three Gram-negative strains (Salmonella typhimurium, E. coli and Pseudomonas aeruginosa) were determined. Activity patterns for the lipidated versions are very complex, dependent on sequence, bacteria and fatty acid. Two reciprocal effects were measured; compared to the parental peptides, some combinations led to a 16-fold improvement whereas other combinations let to a 32-fold reduction in antimicrobial activity. Glycosylation decreased antimicrobial activity by 2 to 16-fold in comparison to A1, respectively on the sugar-peptide combination. PEGylation rendered the peptide inactive. Antimicrobial activity in the presence of 25% human serum of A1 and B1 was reduced 32-fold and 8-fold, respectively. The longer chain fatty acids almost completely restored this activity; however, these fatty acids increased hemolytic activity. B1 modified with C8 increased the therapeutic index by 2-fold for four bacterial strains. Our results suggest that finding the right lipid-peptide combination can lead to improved activity in the presence of serum and potentially more effective drug candidates for animal studies. Glycosylation with the optimal sugar and numbers of sugars at the right peptide position could be an alternative route or could be used in addition to lipidation to counteract solubility and toxicity issues
Equality hypocrisy, inconsistency, and prejudice: The unequal application of the universal human right to equality
No full textIn addition, the author note should have included a license statement, which is provided in this correction.] In Western culture, there appears to be widespread endorsement of Article 1 of the Universal Declaration of Human Rights (which stresses equality and freedom). But do people really apply their equality values equally, or are their principles and application systematically discrepant, resulting in equality hypocrisy? The present study, conducted with a representative national sample of adults in the United Kingdom (N = 2,895), provides the first societal test of whether people apply their value of “equality for all” similarly across multiple types of status minority (women, disabled people, people aged over 70, Blacks, Muslims, and gay people). Drawing on theories of intergroup relations and stereotyping we examined, relation to each of these groups, respondents’ judgments of how important it is to satisfy their particular wishes, whether there should be greater or reduced equality of employment opportunities, and feelings of social distance. The data revealed a clear gap between general equality values and responses to these specific measures. Respondents prioritized equality more for “paternalized” groups (targets of benevolent prejudice: women, disabled, over 70) than others (Black people, Muslims, and homosexual people), demonstrating significant inconsistency. Respondents who valued equality more, or who expressed higher internal or external motivation to control prejudice, showed greater consistency in applying equality. However, even respondents who valued equality highly showed significant divergence in their responses to paternalized versus nonpaternalized groups, revealing a degree of hypocrisy. Implications for strategies to promote equality and challenge prejudice are discussed
Gold nanoparticle charge trapping and relation to organic polymer memory devices.
No full textNanoparticle-based polymer memory devices (PMDs) are a promising technology that could replace conventional silicon-based electronic memory, offering fast operating speeds, simple device structures and low costs. Here we report on the current state of nanoparticle PMDs and review some of the problems that are still present in the field. We also present new data regarding the charging of gold nanoparticles in metal–insulator–semiconductor capacitors, showing that charging is possible under the application of an electric field with a trapped charge density due to the nanoparticles of 3.3x10^12 cm−2.The first author would like to thank the Engineering and Physical Sciences Research Council EPSRC and the National Physical Laboratory NPL for the financial support received for his studentship. The second author would like to thank EPSRC for the financial support Grant No. EP/ E047785/1
Threat, prejudice and stereotyping in the context of Japanese, North Korean, and South Korean intergroup relations.
No full textIntegrated threat theory, realistic conflict theory, and group justification (based on social
identity theory) were evaluated in the international context of Japanese prejudice toward North
Korea and South Korea. Military threat emerged as an important addition to the four threats
outlined by integrated threat theory. Three perceived North Korean threats (realistic [domestic]
threat; intergroup anxiety; military threat) predicted prejudice toward North Korea. North
Korean prejudice predicted negative stereotypes, supporting group-justification theory.
Perceived North Korean realistic [domestic] threat predicted prejudice toward South Korea.
Prejudice toward South Korea predicted negative stereotypes of North Korea, suggesting a
mechanism by which prejudice generalizes
The Soldier's Letter
No full text(Black and White) This postcard is a poem text printed on blue card with a rough image of a military camp at the top. The card provides a preprinted line for the sender to write who the card is "from." The stamp is British, green and cost halfpenny. The postmark information is cut off but the date and time of October 13, 1917 at 10:30 P.M. is clear. The card was sent from Charlie to Mr. and Mrs. Louise in Yorkshire to update them on his whereabouts.This collection previously belonged to Dominic Hibberd, an English biographer most noted for the biographies of Wilfred Owen and Harold Monro, World War I poets. He collected these postcards for research purposes.TRANSCRIPTION; MESSAGE: Just a P. C. to let you know I am still at Wareham. Several have been picked to go away but I havent for once. Hefstonstalls son is a soldier down here, who Fred use to work for. Will write again later Love to all Charlie; SENT TO: Mr [and] Mrs Louise; 38 [illegible] Avenue; [illegible] Road; [illegible] Park; Harrogate; Yorkshir
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