Transgenic RNAi Reveals Essential Function for CTCF in H19 Gene Imprinting

Abstract In The Principles of Constitutionalism, Nicholas Barber provides a sophisticated yet highly readable introduction to fundamental constitutional principles. At the same time, Barber seeks to reorient constitutional theory scholarship away from a mistaken ‘negative’ understanding of constitutionalism towards a ‘positive’ understanding. This essay examines that argument. We suggest that the idea of ‘positive constitutionalism’ has a weaker and a stronger sense. In its weak form, the argument calls for greater attention to what constitutions enable as well as what they restrict, and thus serves as a welcome reminder of the full potential of constitutional principles. However, it cannot be regarded as the correction of a widespread mistake. In its strong form, the argument calls for greater recognition that the state’s essential function lies in advancing the ‘well-being’ of its members. Although this amounts to a significant reorientation, it weakens the theory’s claim to universalism. These tensions indicate limitations to efforts to construct general theories of constitutionalism.

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The Glycine-Phenylalanine-Rich Region Determines the Specificity of the Yeast Hsp40 Sis1

Molecular and Cellular Biology ◽

10.1128/mcb.19.11.7751 ◽

1999 ◽

Vol 19 (11) ◽

pp. 7751-7758 ◽

Cited By ~ 100

Author(s):

Wei Yan ◽

Elizabeth A. Craig

Keyword(s):

Amino Acids ◽

Molecular Chaperones ◽

Rich Region ◽

Critical Determinant ◽

Unique Region ◽

Chimeric Genes ◽

F Region ◽

Initiation Of Translation ◽

J Domain ◽

Essential Function

ABSTRACT Hsp40s are ubiquitous, conserved proteins which function with molecular chaperones of the Hsp70 class. Sis1 is an essential Hsp40 of the cytosol of Saccharomyces cerevisiae, thought to be required for initiation of translation. We carried out a genetic analysis to determine the regions of Sis1 required to perform its key function(s). A C-terminal truncation of Sis1, removing 231 amino acids but retaining the N-terminal 121 amino acids encompassing the J domain and the glycine-phenylalanine-rich (G-F) region, was able to rescue the inviability of a Δsis1 strain. The yeast cytosol contains other Hsp40s, including Ydj1. To determine which regions carried the critical determinants of Sis1 function, we constructed chimeric genes containing portions of SIS1 and YDJ1. A chimera containing the J domain of Sis1 and the G-F region of Ydj1 could not rescue the lethality of the Δsis1 strain. However, a chimera with the J domain of Ydj1 and the G/F region of Sis1 could rescue the strain’s lethality, indicating that the G-F region is a unique region required for the essential function of Sis1. However, a J domain is also required, as mutants expected to cause a disruption of the interaction of the J domain with Hsp70 are inviable. We conclude that the G-F region, previously thought only to be a linker or spacer region between the J domain and C-terminal regions of Hsp40s, is a critical determinant of Sis1 function.

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Time to Be SHY? Some Comments on Sleep and Synaptic Homeostasis

Neural Plasticity ◽

10.1155/2012/415250 ◽

2012 ◽

Vol 2012 ◽

pp. 1-12 ◽

Cited By ~ 56

Author(s):

Giulio Tononi ◽

Chiara Cirelli

Keyword(s):

Synaptic Strength ◽

Universal Function ◽

Systematic Bias ◽

Synaptic Homeostasis ◽

The Face ◽

Essential Function ◽

Function Of Sleep ◽

The Brain

Sleep must serve an essential, universal function, one that offsets the risk of being disconnected from the environment. The synaptic homeostasis hypothesis (SHY) is an attempt to identify this essential function. Its core claim is that sleep is needed to reestablish synaptic homeostasis, which is challenged by the remarkable plasticity of the brain. In other words, sleep is “the price we pay for plasticity.” In this issue, M. G. Frank reviewed several aspects of the hypothesis and raised several issues. The comments below provide a brief summary of the motivations underlying SHY and clarify that SHY is a hypothesis not about specific mechanisms, but about a universal, essential function of sleep. This function is the preservation of synaptic homeostasis in the face of a systematic bias toward a net increase in synaptic strength—a challenge that is posed by learning during adult wake, and by massive synaptogenesis during development.

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H19 gene polymorphisms and Wilms tumor risk in Chinese children: a four‐center case‐control study

Molecular Genetics & Genomic Medicine ◽

10.1002/mgg3.1584 ◽

2021 ◽

Author(s):

Wenya Li ◽

Rui‐Xi Hua ◽

Mi Wang ◽

Da Zhang ◽

Jinhong Zhu ◽

...

Keyword(s):

Gene Polymorphisms ◽

Case Control Study ◽

Wilms Tumor ◽

Case Control ◽

Chinese Children ◽

Tumor Risk ◽

H19 Gene ◽

Control Study

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S-Acylation of Proteins of Coronavirus and Influenza Virus: Conservation of Acylation Sites in Animal Viruses and DHHC Acyltransferases in Their Animal Reservoirs

Pathogens ◽

10.3390/pathogens10060669 ◽

2021 ◽

Vol 10 (6) ◽

pp. 669

Author(s):

Dina A. Abdulrahman ◽

Xiaorong Meng ◽

Michael Veit

Keyword(s):

Influenza Virus ◽

Amino Acid ◽

Ion Channels ◽

Substrate Specificity ◽

Influenza A ◽

3D Structure ◽

Viral Fitness ◽

Amino Acid Substitutions ◽

Essential Function ◽

Animal Reservoirs

Recent pandemics of zoonotic origin were caused by members of coronavirus (CoV) and influenza A (Flu A) viruses. Their glycoproteins (S in CoV, HA in Flu A) and ion channels (E in CoV, M2 in Flu A) are S-acylated. We show that viruses of all genera and from all hosts contain clusters of acylated cysteines in HA, S and E, consistent with the essential function of the modification. In contrast, some Flu viruses lost the acylated cysteine in M2 during evolution, suggesting that it does not affect viral fitness. Members of the DHHC family catalyze palmitoylation. Twenty-three DHHCs exist in humans, but the number varies between vertebrates. SARS-CoV-2 and Flu A proteins are acylated by an overlapping set of DHHCs in human cells. We show that these DHHC genes also exist in other virus hosts. Localization of amino acid substitutions in the 3D structure of DHHCs provided no evidence that their activity or substrate specificity is disturbed. We speculate that newly emerged CoVs or Flu viruses also depend on S-acylation for replication and will use the human DHHCs for that purpose. This feature makes these DHHCs attractive targets for pan-antiviral drugs.

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