Embryo Project Encyclopedia

Mechanism of Notch Signaling: The image depicts a type of cell signaling, in which two animal cells interact and transmit a molecular signal from one to the other. The process results in the production of proteins, which influence the cells as they differentiate, move, and contribute to embryological development. In the membrane of the signaling cell, there is a ligand (represented by a green oval). The ligand functions to activate a change in a receptor molecule. In the receiving cell, there are receptors; in this case, Notch proteins (represented by orange forks). The Notch proteins are embedded in the receiving cell membrane, and they have at least two parts: an intracellular domain (inside the cell) and the receptor (outside the cell). Once the ligand and receptor bind to each other, a protease (represented by the dark red triangle) can sever the intracellular domain from the rest of the Notch receptor. Inside the nucleus of the receiving cell (represented by the gray area) are the cellês DNA (represented by the multi-colored helices) and its transcription factors (blue rectangles). Transcription factors are proteins that bind to DNA to regulate transcription, the first step in gene expression, which eventually yields proteins or other products. Initially, repressor proteins (represented by a red irregular hexagon) prevent transcription factors from allowing transcription. When the severed Notch receptor intracellular domain reaches the nucleus, it displaces the repressor. The transcription factor can then signal for transcription to occur. 1) There is a Notch receptor protein in the membrane of a receiving cell, and a ligand for this receptor (for example, Delta) in the membrane of the signaling cell. When the ligand binds to the receptor, the intracellular domain of the receptor changes shape. 2) Inside the receiving cell, there are proteases. Once the intracellular domain of the receptor changes shape, the protease can bind to it and shear the intracellular domain away from the rest of the receptor molecule. 3) The severed intracellular domain is shuttled to the receiving cell nucleus. Here, the intracellular domain displaces a repressor protein. This allows a transcription factor to initiate DNA transcription. During transcription, DNA is used as a template to create RNA. Following transcription, the process of translation occurs, which uses RNA as a template to create proteins. These proteins influence the behavior, fate, and differentiation of cells, which contribute to normal embryonic development

On March 28, 1978, in Stump v. Sparkman, hereafter Stump, the United States Supreme Court held, in a five-to-three decision, that judges have absolute immunity from lawsuits involving any harm their judicial decisions cause. Linda Sparkman, who was unknowingly sterilized when she was fifteen years old in 1971, sued Harold Stump, the county circuit court judge who signed the petition to allow Sparkman’s mother to have her sterilized. Sparkman’s mother stated to Stump that she wanted her daughter sterilized because of Sparkman’s alleged mental deficiencies and sexual promiscuity. Sparkman argued that Stump violated her Fourteenth Amendment rights to due process because nobody informed her about the nature of the procedure and because Stump did not perform typical court proceedings. Stump argued that, because he was acting within his role as a judge, the doctrine of judicial immunity prevented his liability from lawsuit. Stump strengthened the impunity with which judges can act, including acts found to be unconstitutional, regardless of any rights upon which such actions may infringe.

In 1990, the United States Congress passed the Americans with Disabilities Act, or the ADA, which prohibits discrimination against people with disabilities by employers, governments, or public accommodations. Following gains made during the civil rights movements of the 1900s, people with disabilities sought similar anti-discrimination legislation. The ADA was the culmination of decades of protest and advocacy from the disability rights movement. After the ADA, federal law protected people with an impairment that limited major life functions like sight or mobility from discrimination. The ADA changed the lives of millions of Americans with disabilities by expanding the opportunities they had to work, travel, and participate in their communities legally protected from discrimination.

In United States v. Georgia, the United States Supreme Court held, in a unanimous decision, that the rights protected under the Americans with Disabilities Act, or the ADA, extended to inmates held in state prisons. The Court also abolished sovereign immunity in cases where the Eighth Amendment is involved. The case came about as a result of Tony Goodman, a paraplegic man in a Georgia state prison, who attempted to sue the state under Title II of the ADA. The state of Georgia argued that they were immune to civil suits based on sovereign immunity under the Eleventh Amendment that holds that Congress cannot pass laws that allow non-consenting states to be sued by their people, except for specific circumstances. The US federal government interceded on Goodman's behalf, with the case then being taken up by the Supreme Court. US v. Georgia partially determined the extent to which the ADA covers disabled Americans, improved the situation of disabled individuals in state prison systems, and further eroded the sovereign immunity claimed by states in cases where ADA violations are alleged.

In the 1999 case Olmstead v. L.C., hereafter Olmstead, the United States Supreme Court held in a six to three decision that the forced segregation of people based on disability violated the Americans with Disabilities Act. Two women with mental and intellectual disabilities, Lois Curtis and Elaine Wilson, referred to as L.C. and E.W. in case documents, sued the state of Georgia and Tommy Olmstead, the Commissioner of Georgia who headed the Department of Human Resources, for alleged violations of the Americans with Disabilities Act. The two women each voluntarily admitted themselves to treatment in the state-run Georgia Regional Hospital in Atlanta, Georgia, in 1990. After doctors cleared Curtis and Wilson for transfer into a community-based health setting with non-disabled people, the hospital denied them treatment in a community-based setting due to the financial costs of such treatment and the lack of space. Olmstead protected the rights of people with disabilities outlined in the Americans with Disabilities Act by finding the unjustified segregation of disabled people unconstitutional.

In 1975, the United States Congress passed the Individuals with Disabilities Education Act, referred to as the IDEA, which codified the right of all American children to a free and appropriate public education regardless of disability status. The IDEA requires all public schools that accept federal funds to provide education that meets the needs of students with disabilities at the public expense. Prior to IDEA, many students with disabilities went without any educational opportunities, and many faced confinement in institutions. The IDEA enshrined the right to education for children with disabilities, allowing millions of children to learn in a public-school classroom by setting guidelines for accessibility and the instruction of students with disabilities in American public schools.

In 1972, the United States District Court for the Eastern District of Pennsylvania decided the case of Pennsylvania Association for Retarded Citizens (PARC) v. Commonwealth of Pennsylvania, hereafter PARC v. Pennsylvania. The court ruled that the state could not deny an individual's right to equal access to education based on an intellectual or developmental disability status. PARC brought the case against the state of Pennsylvania on behalf of fourteen families with intellectually disabled children who were unable to access to public schools based on their child’s disability. PARC challenged state laws that permitted schools to deny education to children who do not reach the mental age of five, or the average intelligence of people aged five, by the time they begin first grade. Both sides settled following the testimony of expert witnesses on PARC's behalf, and the US District Court approved the consent decree. PARC v. Pennsylvania was one of the first cases to establish that people born with an intellectual disability should have the same access to education as the rest of the population.

In Mills v. Board of Education of District of Columbia (1972), the United States District Court for the District of Columbia held that students with disabilities are entitled to an education, and that education cannot be denied based on the accommodations’ additional cost to the school. Mills was a class action lawsuit brought to the court on behalf of seven children denied public education by the District of Columbia School District because of their disabilities and the cost of accommodations the school would incur to educate them. US District Court Judge Joseph Cornelius Waddy presided over the case and ruled in favor of the students, finding that they were not given due process prior to expulsion from the school. Mills was one of the first cases in the US that guaranteed the right of students with any disability to a public education, regardless of the cost to the school system, and led to comprehensive federal legislation protecting disabled children's right to free public education.

'On the Permanent Life of Tissues outside of the Organism' reports Alexis Carrel's 1912 experiments on the maintenance of tissue in culture media. At the time, Carrel was a French surgeon and biologist working at the Rockefeller Institute in New York City. In his paper, Carrel reported that he had successfully maintained tissue cultures, which derived from connective tissues of developing chicks and other tissue sources, by serially culturing them. Among all the tissue cultures Carrel reported, one was maintained for more than two months, whereas previous efforts had only been able to keep tissues in vitro for three to fifteen days. Carrel’s experiments contributed to the development of long-term tissue culture techniques, which were useful in the study of embryology and eventually became instrumental in stem cell research. Despite later evidence to the contrary, Carrel believed that as long as the tissue culture method was accurately applied, tissues kept outside of the organisms should be able to divide indefinitely and have permanent life.

Christiane Nusslein-Volhard studied how genes control embryonic development in flies and in fish in Europe during the twentieth and twenty-first centuries. In the 1970s, Nusslein-Volhard focused her career on studying the genetic control of development in the fruit fly Drosophila melanogaster. In 1988, Nusslein-Volhard identified the first described morphogen, a protein coded by the gene bicoid in flies. In 1995, along with Eric F. Wieschaus and Edward B. Lewis, she received the Nobel Prize in Physiology or Medicine for the discovery of genes that establish the body plan and segmentation in Drosophila. Nusslein-Volhard also investigated the genetic control of embryonic development to zebrafish, further generalizing her findings and helping establishing zebrafish as a model organism for studies of vertebrate development.