Popular sovereignty is a doctrine rooted in the belief that each citizen has sovereignty over themselves. Citizens may unite and offer to delegate a portion of their sovereign powers and duties to those who wish to serve as officers of the state, contingent on the officers agreeing to serve according to the will of the people. In the United States, the term has been used to express this concept in constitutional law, it was used during the 19th century in reference to a proposed solution to the debate over the expansion of slavery. The proposal would have given the power to determine the legality of slavery to the inhabitants of the territory seeking statehood, rather than to Congress; the concept of popular sovereignty did not originate in North America. The American contribution was the translation of these ideas into a formal structure of government. Before the American Revolution, there were few examples of a people creating their own government. Most had experienced government as an inheritance -- as other expressions of power.
The American Revolution resulted in a government based on popular sovereignty, the first large-scale establishment of this concept. The early Americans supported the contention that governments were legitimate only if they were based on popular sovereignty; the concept unified and divided post-Revolutionary American thinking about government and the basis of the Union. Questions were raised over its precise meaning, permissible actions and the will of a collective sovereign. In 18th-century European political thought, "the people" excluded most of the population; the early American republic disenfranchised women and those lacking sufficient property denying citizenship to slaves and other non-whites. According to historian Ronald Formisano, "Assertions of the peoples' sovereignty over time contained an unintended dynamic of raising popular expectations for a greater degree of popular participation and that the peoples' will be satisfied." In 1846, as the dispute over slavery in the United States developed in the wake of the Mexican–American War, popular sovereignty became the foundation of a proposed resolution to slavery in the country.
At the war's end, the United States acquired lands held by Mexico. The effort to incorporate these lands into the United States uncovered long-simmering disputes about the extension of slavery – whether it would be permitted, abolished or perpetuated in the newly-acquired areas. Attempts to resolve the issue in Congress led to gridlock. Several Congressional leaders, in an effort to resolve the deadlock over slavery as a condition for admission or administration of the territories, searched for a middle ground. To some moderates, slavery in the territories was not a matter for Congress to resolve. Popular sovereignty became part of the rhetoric for leaving to residents of the new American territories the decision to accept or reject slavery; this formed a middle ground between proponents of a limitation on slavery's spread to the territories and those opposing limitations, tying into the widespread American assumption that the people were sovereign. According to historian Michael Morrison, the "idea of local self-determination, or, as it would become known, popular sovereignty" first began to occupy the attention of Congress in 1846 and 1847.
In modern historiography, Illinois senator Stephen A. Douglas is most associated with popular sovereignty as a solution to the extension of slavery in the territories. Douglas's biographer, historian Robert W. Johannsen, wrote that Douglas was chairman of the Committee on Territories in both the House and Senate, he discharged the responsibilities of his position with single-minded devotion.... During the debates over the organization of the Mexican Cession, Douglas evolved his doctrine of popular sovereignty, from that time on it was irrevocably linked to his interest in the territories and in the West, his commitment to popular sovereignty was the deeper because he recognized in it a formula that would bridge the differences between the North and South on the slavery question, thus preserving the Union. The term "popular sovereignty" was not coined by Douglas. Today it is more associated with Douglas, its connection to the failed attempt to accommodate slavery gave the term its present pejorative connotation.
Douglas "ultimately became the victim of the politics he sought to remove from territorial policy" by advancing the idea of popular sovereignty: "His efforts were not judged in terms of their impact on the needs and desires of the territories.... Rather, they were appraised in terms of their relation to the power struggle between North and South and to the issue of slavery. Despite Douglas's intentions, the territories continued to be but pawns in a larger political controversy." The colonists' struggle for equality with the King of Great Britain was enshrined in the American Declaration of Independence and was common knowledge in the United States after the American Revolution. Inaugural Chief Justice John Jay, in Chisholm v. Georgia, illustrate what would com
Thomas Usborne, MP, was an English Conservative Party politician. He was born in Limerick and studied successively at Harrow School and at Trinity College, Cambridge where he obtained an MA degree, he was elected to the House of Commons as the Member of Parliament for the Chelmsford Division of Essex at an unopposed by-election in 1892, following the death of the sitting MP William Beadel. Usborne was re-elected at the general election in July 1892, held the seat until he stood down at the 1900 general election. Hansard 1803–2005: contributions in Parliament by Thomas Usborne
An intein is a segment of a protein, able to excise itself and join the remaining portions with a peptide bond in a process termed protein splicing. Inteins have been called "protein introns". Intein-mediated protein splicing occurs after the intein-containing mRNA has been translated into a protein; this precursor protein contains three segments—an N-extein followed by the intein followed by a C-extein. After splicing has taken place, the resulting protein contains the N-extein linked to the C-extein; the first intein was discovered in 1988 through sequence comparison between the Neurospora crassa and carrot vacuolar ATPase and the homologous gene in yeast, first described as a putative calcium ion transporter. In 1990 Hirata et al. demonstrated that the extra sequence in the yeast gene was transcribed into mRNA and removed itself from the host protein only after translation. Since inteins have been found in all three domains of life and in viruses. Many genes have unrelated intein-coding segments inserted at different positions.
For these and other reasons, inteins are sometimes called selfish genetic elements, but it may be more accurate to call them parasitic. According to Dawkins' gene centered view of evolution, most genes are "selfish" only insofar as to compete with other genes or alleles but they fulfill a function for the organisms, whereas "parasitic genetic elements", at least do not make a positive contribution to the fitness of the organism. Within the database of all known inteins, 113 known inteins are present in eukaryotes with minimum length of 138 amino acids and maximum length of 844 amino acids; the first intein was found encoded within the VMA gene of Saccharomyces cerevisiae. They were found in fungi and in diverse proteins as well. A protein distantly related to known inteins containing protein, but related to metazoan hedgehog proteins, has been described to have the intein sequence from Glomeromycota. Many of the newly described inteins contain homing endonucleases and some of these are active.
The abundance of intein in fungi indicates lateral transfer of intein-containing genes. While in eubacteria and archaea, there are 289 and 182 known inteins. Not most intein in eubacteria and archaea are found to be inserted into nucleic acid metabolic protein, like fungi; the mechanism for the splicing effect is a occurring analogy to the technique for chemically generating medium-sized proteins called native chemical ligation, developed at the same time as inteins were discovered. The process begins with an N-O or N-S shift when the side chain of the first residue of the intein portion of the precursor protein nucleophilically attacks the peptide bond of the residue upstream to form a linear ester intermediate. A transesterification occurs when the side chain of the first residue of the C-extein attacks the newly formed ester to free the N-terminal end of the intein; this forms a branched intermediate in which the N-extein and C-extein are attached, albeit not through a peptide bond. The last residue of the intein is always an asparagine, the amide nitrogen atom of this side chain cleaves apart the peptide bond between the intein and the C-extein, resulting in a free intein segment with a terminal cyclic imide.
The free amino group of the C-extein now attacks the ester linking the N- and C-exteins together. An O-N or S-N shift produces the functional, ligated protein. Inteins are efficient at protein splicing, they have accordingly found an important role in biotechnology. There are more than 200 inteins identified to date. Inteins have been engineered for particular applications such as protein semisynthesis and the selective labeling of protein segments, useful for NMR studies of large proteins. Pharmaceutical inhibition of intein excision may be a useful tool for drug development, it has been suggested that inteins could prove useful for achieving allotopic expression of certain hydrophobic proteins encoded by the mitochondrial genome, for example in gene therapy. The hydrophobicity of these proteins is an obstacle to their import into mitochondria. Therefore, the insertion of a non-hydrophobic intein may allow this import to proceed. Excision of the intein after import would restore the protein to wild-type.
Affinity tags have been used to purify recombinant proteins, as they allow the accumulation of recombinant protein with little impurities. However, the affinity tag must be removed by proteases in the final purification step; the extra proteolysis step raises the problems of protease specificity in removing affinity tags from recombinant protein, the removal of the digestion product. This problem can be avoided by fusing an affinity tag to self-cleavable inteins in a controlled environment; the first generation of expression vectors of this kind used modified Saccharomyces cerevisiae VMA intein. Chong et al. used a chitin binding domain from Bacillus circulans as an affinity tag, fused this tag with a modified Sce VMA intein. The modified intein undergoes a self-cleavage reaction at its N-terminal peptide linkage with 1,4-dithiothreitol, β-mercaptoethanol, or cystine at low temperatures over a bro