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Related Concept Videos

Transcription Factors02:16

Transcription Factors

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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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Factors Affecting Solubility04:01

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Compared with pure water, the solubility of an ionic compound is less in aqueous solutions containing a common ion (one also produced by dissolution of the ionic compound). This is an example of a phenomenon known as the common ion effect, which is a consequence of the law of mass action that may be explained using Le Chȃtelier’s principle. Consider the dissolution of silver iodide:
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Transcription Elongation Factors02:35

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Transcription elongation is a dynamic process that alters depending upon the sequence heterogeneity of the DNA being transcribed. Hence, it is not surprising that the elongation complex's composition also varies along the way while transcribing a gene.
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Factors Affecting Drug Distribution: Miscellaneous Factors01:19

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Drug distribution in the human body is a complex process influenced by various individual factors, including age, pregnancy, obesity, diet, body water composition, pH levels, and specific disease conditions.
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Electrolytes: van't Hoff Factor03:08

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Colligative Properties of Electrolytes
The colligative properties of a solution depend only on the number, not on the identity, of solute species dissolved. The concentration terms in the equations for various colligative properties (freezing point depression, boiling point elevation, osmotic pressure) pertain to all solute species present in the solution. Nonelectrolytes dissolve physically without dissociation or any other accompanying process. Each molecule that dissolves yields one...
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Factors Affecting Protein-Drug Binding: Drug-Related Factors01:18

Factors Affecting Protein-Drug Binding: Drug-Related Factors

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Drug binding to proteins is a complex phenomenon influenced by various drug-related factors, each playing a significant role in the interaction between drugs and proteins within the body.
One crucial factor in drug-protein binding is the drug's lipophilicity or its affinity for fat. More lipophilic drugs tend to have higher binding extents. For example, highly lipophilic drugs like cloxacillin exhibit substantial protein binding, with as much as 95% of the drug binding to proteins. In...
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Bypassing pan-enterovirus host factor PLA2G16.

Jim Baggen1, Yue Liu2, Heyrhyoung Lyoo1

  • 1Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL, Utrecht, The Netherlands.

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|July 20, 2019
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Enteroviruses can evade the host factor phospholipase A2 (PLA2G16) by using sulfated glycosaminoglycans (sGAGs) as a second receptor. This interaction destabilizes the virus, aiding its escape and replication.

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Area of Science:

  • Virology
  • Molecular Biology
  • Structural Biology

Background:

  • Enteroviruses cause significant human disease.
  • Adipose-specific phospholipase A2 (PLA2G16) is a host factor and drug target for enteroviruses.
  • Enterovirus D68 (EV-D68) utilizes sialic acid but can also use other receptors.

Purpose of the Study:

  • To investigate mechanisms by which EV-D68 evades PLA2G16.
  • To identify alternative glycan receptors for EV-D68.
  • To elucidate the structural basis of EV-D68 entry and replication.

Main Methods:

  • Haploid genetic screening to identify viral receptors.
  • Cryo-electron microscopy (cryo-EM) for structural analysis.
  • Analysis of viral genome release and virion destabilization.

Main Results:

  • Sulfated glycosaminoglycans (sGAGs) were identified as a second glycan receptor for a dual-binding EV-D68 strain.
  • Engagement of sGAGs allows the virus to bypass PLA2G16.
  • Cryo-EM revealed that sGAGs induce structural changes in the virion, enlarging openings for genome release.

Conclusions:

  • Enteroviruses can evolve to evade host factors like PLA2G16.
  • sGAGs serve as an alternative receptor that facilitates EV-D68 entry and replication.
  • Virion destabilization through sGAG engagement is a novel mechanism for enterovirus evasion.