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Related Concept Videos

T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
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What is Natural Selection?01:32

What is Natural Selection?

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Natural selection is an evolutionary process in which individuals with survival-promoting traits reproduce at higher rates. These favorable traits become more common within a population or species. Naturally selected traits initially arise via random genetic mutations. In order for selection to occur, there must be variation within a population, the trait controlling the variation must be heritable, and there must be an evolutionary advantage for variation in the trait.
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Antibiotic Selection00:57

Antibiotic Selection

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Overview
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Types of Selection01:46

Types of Selection

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Natural selection influences the frequencies of particular alleles and phenotypes within populations in several different ways. Primarily, natural selection can be directional, stabilizing, or disruptive. Directional selection favors one extreme trait and shifts the population towards that phenotype while selecting against individuals displaying alternate traits. Stabilizing selection favors an intermediate trait with a narrow range of variation. Deviation from the optimal phenotype towards an...
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Frequency-dependent Selection01:21

Frequency-dependent Selection

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When the fitness of a trait is influenced by how common it is (i.e., its frequency) relative to different traits within a population, this is referred to as frequency-dependent selection. Frequency-dependent selection may occur between species or within a single species. This type of selection can either be positive—with more common phenotypes having higher fitness—or negative, with rarer phenotypes conferring increased fitness.
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Limits to Natural Selection01:38

Limits to Natural Selection

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Organisms that are well-adapted to their environment are more likely to survive and reproduce. However, natural selection does not lead to perfectly adapted organisms. Several factors constrain natural selection.
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Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids
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Selection and redesign for high selectivity of membrane-active antimicrobial peptides from a dedicated

Tomislav Rončević1, Damir Vukičević2, Lucija Krce1

  • 1Department of Physics, Faculty of Science, University of Split, Split, Croatia.

Biochimica Et Biophysica Acta. Biomembranes
|February 3, 2019
PubMed
Summary

Researchers developed a computational tool to design safer antimicrobial peptides (AMPs) that kill bacteria without harming host cells. This approach identified novel peptide candidates, demonstrating a promising strategy for new antibiotic development.

Keywords:
Anuran antimicrobial peptidesPeptide modificationsSelectivity index

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Area of Science:

  • Biochemistry and Molecular Biology
  • Computational Chemistry
  • Drug Discovery

Background:

  • Antimicrobial peptides (AMPs) show promise as antibiotics due to low resistance development but often exhibit host cell toxicity.
  • Developing selective AMPs through traditional modification is costly and inefficient.

Purpose of the Study:

  • To computationally screen and design novel, selective antimicrobial peptides with reduced host cell toxicity.
  • To validate the efficacy and safety of computationally designed peptides.

Main Methods:

  • Modified the 'Mutator' computational tool, incorporating quantitative structure-activity relationship (QSAR) criteria, to analyze multiple peptide sequences.
  • Screened the Database of Anuran Defense Peptides (DADP) to identify candidate sequences for modification.
  • Synthesized and experimentally tested two novel peptide variants (Dadapins) using flow cytometry and atomic force microscopy (AFM).

Main Results:

  • The modified Mutator algorithm successfully proposed 8 potentially selective AMPs (Dadapins) from the DADP.
  • Tested Dadapins demonstrated potent antibacterial activity by disrupting bacterial membranes.
  • Experimental validation confirmed Dadapins were non-toxic to host cells.

Conclusions:

  • The enhanced computational approach effectively designs selective antimicrobial peptides with low host toxicity.
  • This strategy offers a cost-effective and efficient method for developing next-generation antibiotics.