Receptor (biochemistry)

In biochemistry and pharmacology, receptors are chemical structures, composed of protein, that receive and transduce signals that may be integrated into biological systems. These signals are chemical messengers, which bind to a receptor, they cause some form of cellular/tissue response, e.g. a change in the electrical activity of a cell. There are three main ways the action of the receptor can be classified: relay of signal, amplification, or integration. Relaying sends the signal onward, amplification increases the effect of a single ligand, integration allows the signal to be incorporated into another biochemical pathway. In this sense, a receptor is a protein-molecule that recognizes and responds to endogenous chemical signals. For example, an acetylcholine receptor recognizes and responds to its endogenous ligand, acetylcholine. However, sometimes in pharmacology, the term is used to include other proteins that are drug targets, such as enzymes and ion channels. Receptor proteins can be classified by their location.

Transmembrane receptors include ion channel-linked receptors, G protein-linked hormone receptors, enzyme-linked hormone receptors. Intracellular receptors are those found inside the cell, include cytoplasmic receptors and nuclear receptors. A molecule that binds to a receptor is called a ligand, can be a protein or peptide, or another small molecule such as a neurotransmitter, pharmaceutical drug, calcium ion or parts of the outside of a virus or microbe; the endogenously designated -molecule for a particular receptor is referred to as its endogenous ligand. E.g. the endogenous ligand for the nicotinic acetylcholine receptor is acetylcholine but the receptor can be activated by nicotine and blocked by curare. Receptors of a particular type are linked to a specific cellular biochemical pathways that correspond to the signal. While numerous receptors are found in most cells, each receptor will only bind with ligands of a particular structure; this has been analogously compared to how locks will only accept shaped keys.

When a ligand binds to a corresponding receptor, it activates or inhibits the receptor's associated biochemical pathway. The structures of receptors are diverse and include the following major categories, among others: Type 1: Ligand-gated ion channels – These receptors are the targets of fast neurotransmitters such as acetylcholine and GABA, they have a heteromeric structure in that each subunit consists of the extracellular ligand-binding domain and a transmembrane domain where the transmembrane domain in turn includes four transmembrane alpha helices. The ligand-binding cavities are located at the interface between the subunits. Type 2: G protein-coupled receptors – This is the largest family of receptors and includes the receptors for several hormones and slow transmitters e.g. dopamine, metabotropic glutamate. They are composed of seven transmembrane alpha helices; the loops connecting the alpha helices form extracellular and intracellular domains. The binding-site for larger peptide ligands is located in the extracellular domain whereas the binding site for smaller non-peptide ligands is located between the seven alpha helices and one extracellular loop.

The aforementioned receptors are coupled to different intracellular effector systems via G proteins. Type 3: Kinase-linked and related receptors – They are composed of an extracellular domain containing the ligand binding site and an intracellular domain with enzymatic-function, linked by a single transmembrane alpha helix; the insulin receptor is an example. Type 4: Nuclear receptors – While they are called nuclear receptors, they are located in the cytoplasm and migrate to the nucleus after binding with their ligands, they are composed of a C-terminal ligand-binding region, a core DNA-binding domain and an N-terminal domain that contains the AF1 region. The core region has two zinc fingers that are responsible for recognizing the DNA sequences specific to this receptor; the N terminus interacts with other cellular transcription factors in a ligand-independent manner. Steroid and thyroid-hormone receptors are examples of such receptors. Membrane receptors may be isolated from cell membranes by complex extraction procedures using solvents, and/or affinity purification.

The structures and actions of receptors may be studied by using biophysical methods such as X-ray crystallography, NMR, circular dichroism, dual polarisation interferometry. Computer simulations of the dynamic behavior of receptors have been used to gain understanding of their mechanisms of action. Ligand binding is an equilibrium process. Ligands bind to receptors and dissociate from them according to the law of mass action in the following equation, for a ligand L and receptor, R; the brackets around chemical species denote their concentrations. + ⇌ K d One measure of how well a molecule fits a receptor is its binding affinity, inversely related to the dissociation constant Kd. A good fit corresponds with high low Kd; the final biological response, is only achieved after a significant number of r

Cut and fill

In earthmoving and fill is the process of constructing a railway, road or canal whereby the amount of material from cuts matches the amount of fill needed to make nearby embankments, so minimizing the amount of construction labor. Cut slopes are created greater than a slope of two to one. Cut sections of roadway or rail are characterized by the roadway being lower in elevation than the surrounding terrain. From an operational standpoint there are unique environmental effects associated with cut sections of roadway. For example, air pollutants can concentrate in the ‘'valleys'‘ created by the cut section. Conversely, noise pollution is mitigated by cut sections since an effective blockage of line of sight sound propagation is created by the depressed roadway design. Fill sections trackbed. Environmental effects of fill sections are favorable with respect to air pollution dispersal, but in the matter of sound propagation, exposure of nearby residents is increased, since sound walls and other forms of sound path blockage are less effective in this geometry.

There are a variety of reasons for creating fills, among them reduction of grade along a route or elevation of the route above water, swampy ground, or areas where snow drifts collect. Fills can be used to cover tree stumps, rocks, or unstable soil, in which case material with a higher bearing capacity is placed on top of the obstacle in order to carry the weight of the roadway or railway and reduce differential settlement; the practice of cut-and-fill was utilized to construct tracks along rolling terrain across the British Isles. It was performed on new dwellings for returned soldiers in Ireland at the end of World War II; this application was developed by Irish railway engineer Lachlan J. Boland, who saw the benefits of introducing railway practices to residential construction. A number of software products are available for calculating fill. A simple approach involves defining different earthworks features in a software program and adjusting elevations manually to calculate the optimal cut and fill.

More sophisticated software is able to automatically balance cut and fill and take account of materials. Software that can do this falls under the broad category of earthworks estimation software

WTC Wharf

WTC Wharf is a twelve-storey office complex on the north bank of the Yarra River in Melbourne, Australia. On 19 December 1978, the Government of Victoria passed the Port of Melbourne Act 1978, vesting the Port of Melbourne Authority with authority to construct and operate a World Trade Centre in the Port of Melbourne; the centre, an example of Brutalist architecture, was built in the early 1980s and opened in 1983. On 30 June 1994, Melbourne's first casino, Crown Casino opened in the World Trade Centre; the location was a temporary measure while Crown's permanent home, the Crown Casino and Entertainment Complex was constructed across the Yarra river at Southbank In 1997, the centre hosted a temporary exhibition of waxworks from the Madame Tussauds wax museum in London. The building houses some offices of the headquarters of Victoria Police, the Victoria Police Museum, a collection of exhibits and memorabilia from over 150 years of policing in Victoria, it houses offices for companies, including Thales Australia.

The WTC shopping centre is undergoing redevelopment, including the proposed installation of an environmentally friendly air-conditioning system using water from the Yarra River. Further redevelopment plans include construction of restaurants, cafes, a hotel, a wine store, a function centre, a health and beauty centre. WTC Wharf website