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Virology

Virology

Virology is the study of viruses and their properties. Virology is both the study of how a virus can affect a cell, and the biological and biochemical properties of a virus. Biochemically, viruses are very different to other living organisms and there is a great debate as to whether a virus can actually be considered alive. Most viruses consist of nucleic acid inside a protein shell, covered with antigens. Some viruses are more complex, and have a helix structure with 'off shoots', similar to a lunar lander, which invade cells with great effect. In the immune system, antigens, which allow a virus to invade a cell, are 'neutralised' (bound to with an inert molecule) by antibodies. The presence of antigens, or antibodies, and their relative abundance can be measured using an ELISA test (Enzyme Linked Immuno-Sorbent Assay). The presence of a virus can be measured using a technique named fluorescence microscopy. By using a conjugated (joined) monoclonal antibody and fluorescent molecule, which will attach to a virus's antigen covered protein shell, the presence of a virus can be determined under a UV microscope. The fluorescent color should appear in virus affected cells as they push out viruses from the cell using the endoplasmic reticular system of a cell, and also in the cytoplasm], however not in the nucleus (only the nucleic acid part of a virus penetrates the nuclear membrane). Common viruses include: Influenza virus, Hepatitis viruses, Herpes virus (Coldsore family (Herpes Simplex)), Varicella (the family to which 'chicken pox' (Varicella Zoster) belongs) and HIV. Properties include:
- Viral replication
- Viral pathogenesis
- Viral immunology
- Viral vaccines
- Diagnostic methods
- Antiviral chemotherapy
- Infection control measures
- Virus outbreaks

Virus (biology)

:This article is concerned with virus as a biological infectious particle; for other uses see virus (disambiguation). virus (disambiguation) A virus is a microscopic parasite that infects cells in biological organisms. Viruses are obligate intracellular parasites; they can reproduce only by invading and controlling other cells as they lack the cellular machinery for self-reproduction. The term virus usually refers to those particles that infect eukaryotes (multi-celled organisms and many single-celled organisms), whilst the term bacteriophage or phage is used to describe those infecting prokaryotes (bacteria and bacteria-like organisms lacking a nucleus). Typically these particles carry a small amount of nucleic acid (either DNA or RNA, but not both) surrounded by some form of protective coat consisting of proteins, lipids, glycoproteins or a combination. Importantly, viral genomes code not only for the proteins needed to package its genetic material, but for proteins needed by the virus during its life cycle (the term "life cycle" is used loosely here—see Living or non-living?).
Origins and Beginnings
The origins of viruses are not entirely clear and there may not be a single mechanism that can account for all viruses. Some of the smaller viruses that have only a few genes may have originated from host organisms. Their genetic material could have been derived from transferrable elements like plasmids or transposons. Viruses with large genomes may represent extremely reduced microbes which established symbiotic relations with host organisms, allowing the loss of some genes needed for existence independent of a host. Other infectious particles which are even simpler in structure than viruses include viroids, virusoids, and prions.
Size, structure, and anatomy
Virus particles comprise a nucleic acid genome that may be either DNA or RNA, single- or double-stranded, and positive or negative sense. This is surrounded (encapsidated) by a protective coat of protein called a capsid. The viral capsid may be either spherical or helical and is composed of proteins encoded by the viral genome. In helical viruses, the capsid protein (frequently called the nucleocapsid protein) binds directly to the viral genome. For example, in the case of the measles virus, one nucleocapsid protein binds every six bases of RNA to form a helix approximately 1.3 micrometers in length. This complex of protein and nucleic acid is called the nucleocapsid, and, in the case of the measles virus, is enclosed in a lipid "envelope" acquired from the host cell, in which virus-encoded glycoproteins are embedded. These are responsible for binding to and entering the host cell at the start of a new infection. Spherical virus capsids completely enclose the viral genome and do not generally bind as tightly to the nucleic acid as helical capsid proteins do. These structures can range in size from less than 20 nanometers up to 400 nanometers and are composed of viral proteins arranged with icosahedral symmetry. Icosahedral architecture is the same principle employed by R. Buckminster-Fuller in his geodesic dome, and it is the most efficient way of creating an enclosed robust structure from multiple copies of a single protein. The number of proteins required to form a spherical virus capsid is denoted by the "T-number" whereby 60t proteins are necessary. In the case of the hepatitis B virus, the T-number is 4, therefore 240 proteins assemble to form the capsid. As in the helical viruses, the spherical virus capsid may be enclosed in a lipid envelope, although frequently spherical viruses are not enveloped, and the capsid proteins themselves are directly involved in attachment and entry into the host cell. The complete virus particle is referred to as a virion. A virion is little more than a gene transporter, and components of the envelope and capsid provide the mechanism for injecting the viral genome into a host cell..
Replication
Because viruses are acellular and do not have their own metabolism, they must utilize the machinery and metabolism of the host to reproduce. Before a virus has entered a host cell, it is called a virion — a package of viral genetic material. Virions can be passed from host to host either through direct contact or through a vector, or carrier. Inside the organism, the virus can enter a cell in various ways. Bacteriophages—bacterial viruses—attach to the cell wall surface in specific places. Once attached, enzymes make a small hole in the cell wall, and the virus injects its DNA into the cell. Other viruses (such as HIV) enter the host via endocytosis, the process whereby cells take in material from the external environment. After entering the cell, the virus's genetic material begins the destructive process of causing the cell to produce new viruses. There are three different ways genetic information contained in a viral genome can be reproduced. The form of genetic material contained in the viral capsid, the protein coat that surrounds the nucleic acid, determines the exact replication process. Some viruses have DNA, which once inside the host cell is replicated by the host along with its own DNA. There are two different replication processes for viruses containing RNA. In the first process, the viral RNA is directly copied using an enzyme called RNA replicase. This enzyme then uses that RNA copy as a template to make hundreds of duplicates of the original RNA. A second group of RNA-containing viruses, called the retroviruses, uses the enzyme reverse transcriptase to synthesize a complementary strand of DNA so that the virus's genetic information is contained in a molecule of DNA rather than RNA. The viral DNA can then be further replicated using the resources of the host cell.
Outline
#Attachment, sometimes called absorption: The virus attaches to receptors on the host cell wall. #Injection: The nucleic acid of the virus moves through the plasma membrane and into the cytoplasm of the host cell. The capsid of a phage, a bacterial virus, remains on the outside. In contrast, many viruses that infect animal cells enter the host cell intact. #Replication: The viral genome contains all the information necessary to produce new viruses. Once inside the host cell, the virus induces the host cell to synthesize the necessary components for its replication. #Assembly: The newly synthesized viral components are assembled into new viruses. #Release: Assembled viruses are released from the cell and can now infect other cells, and the process begins again. When the virus has taken over the cell, it immediately causes the host to begin manufacturing the proteins necessary for virus reproduction. Some viruses, like herpes, cause the host to produce three kinds of proteins: early proteins, enzymes used in nucleic acid replication; late proteins, proteins used to construct the virus coat; and lytic proteins, enzymes used to break open the cell for viral exit. The final viral product is assembled spontaneously, that is, the parts are made separately by the host and are joined together by chance. This self-assembly is often aided by molecular chaperones, or proteins made by the host that help the capsid parts come together. The new viruses then leave the cell either by exocytosis or by lysis. Envelope-bound animal viruses cause the host's endoplasmic reticulum to make certain proteins, called glycoproteins, which then collect in clumps along the cell membrane. The virus is then discharged from the cell at these exit sites, referred to as exocytosis. On the other hand, bacteriophages must break open, or lyse, the cell to exit. To do this, the phages have a gene that codes for an enzyme called lysozyme. This enzyme breaks down the cell wall, causing the cell to swell and burst. The new viruses are released into the environment, killing the host cell in the process.
Lifeform debate
A virus makes use of existing host enzymes and other molecules of a host cell to create more virus particles (virions). Some viruses encode part or all of their own genome replication machinery and are not entirely reliant on host polymerases for replication of their genetic material. Such viruses can be targeted by antiviral drugs that specifically inhibit the virally encoded replicase molecule(s). Viruses rely on host cell ribosomes for the production of viral proteins and utilize several distinct strategies to make the host cell synthesize the viral proteins. For example, at least some +RNA viruses use Internal Ribosome Entry Site IRES segments to drive the translation from their genomic +RNA molecule. Viruses are neither unicellular nor multicellular organisms; they are somewhere between being living and non-living. Viruses have genes and show inheritance, but are reliant on host cells to produce new generations of viruses. Many viruses have similarities to complex molecules. Because viruses are dependent on host cells for their replication they are generally not classified as "living". Whether or not they are "alive", they are obligate parasites, and have no form which can reproduce independently of their host. Like most parasites, they have a specific host range, sometimes specific to one species (or even limited cell types of one species) and sometimes more general. Some viruses form by self-assembly of protein and nucleic acid molecules. These macromolecules are assembled within host cells from smaller organic compounds. Virus self-assembly has implications for the study of the origin of life. Some viruses also incorporate lipids from the host cell membrane when their core protein-nucleic acid complex buds from the surface of a host cell. Concerning whether viruses are alive or not, if the requirement for autonomous self-reproduction is abandoned, it can be argued strongly that viruses are indeed alive. Some small viruses are more efficient than most cellular life forms as their ratio of functions to working parts is so high. If viruses are alive then the prospect of creating artificial life is enhanced or at least the standards required to call something artificially alive are reduced.
Study and applications

Exploring basic cellular processes
Viruses are important to the study of molecular and cellular biology because they provide simple systems that can be used to manipulate and investigate the functions of cells. The study and use of viruses have provided valuable information about many aspects of cell biology. For example, viruses have further simplified the study of genetics and have deepened our understanding of the basic mechanisms of molecular genetics (DNA replication, transcription, RNA processing), Translation (genetics), protein transport, and immunology.
Genetic engineering
Geneticists regularly use viruses as vectors to introduce genes into cells that they are studying. Attempts to treat human diseases through the use of viruses as tools of genetic engineering is one goal of gene therapy.
Materials science and nanotechnology
Scientists at MIT have recently been able to use viruses to create metallic wires, and they have the potential to be used for binding to exotic materials, self-assembly, liquid crystals, solar cells, batteries, fuel cells, and many other interesting areas. The essential idea is to use a virus with a known protein on its surface. The location of the code for this protein is in a known location in the DNA, and by randomizing that sequence it can create a phage library of millions of different viruses, each with a different protein expressed on its surface. By using natural selection, one can then find a particular strain of this virus which has a binding affinity for a given material. For example, one can isolate a virus which has a high affinity for gold. Taking this virus and growing gold nanoparticles around it results in the gold nanoparticles being incorporated into the virus coat, resulting in a gold wire of precise length and shape with biological origins. Current thinking is that viruses will one day be created which can act as agents on behalf of bio-mechanical healing devices giving humans or other animals extended life.
Human viral diseases
Examples of diseases caused by viruses include the common cold, which is caused by any one of a variety of related viruses; smallpox; AIDS, which is caused by HIV; and cold sores, which are caused by herpes simplex. Other connections are being studied such as the connection of HHV-6 in organic neurological diseases such as Multiple Sclerosis and Chronic Fatigue Syndrome. Recently it has been shown that cervical cancer is caused at least partly by papillomavirus (which causes papillomas, or warts), representing the first significant evidence in humans for a link between cancer and an infective agent. There is current controversy over whether borna virus, previously thought of primarily as the causative agent of neurological disease in horses, could be responsible for psychiatric illness in humans. The relative ability of viruses to cause disease is described in terms of virulence. The ability of viruses to cause devastating epidemics in human societies has led to concern that viruses will be weaponized for biological warfare. Further concern was raised by the successful recreation of a virus in a laboratory. Much concern revolves around the smallpox virus, which has devastated numerous societies throughout history, and today is extinct in the wild. In fact, smallpox has been used in a crude form of biological warfare by British colonists against a tribe of Native Americans. This episode of biological warfare was part of a larger phenomenon of Native American populations being devastated by contagious diseases, particularly smallpox, brought to the Americas by European colonists. It is unclear how many Native Americans were killed by smallpox after the arrival of Columbus in the Americas, but it may have been very large. The damage done by this disease may have significantly aided European attempts to displace or conquer the native population. Jared Diamond argued in his book Guns, Germs, and Steel that highly contagious diseases develop in agricultural societies and regularly aid those societies when they expand into the territories of non-agricultural peoples. Of all types of virus, the most deadly are known as filovirus. The Filovirus group consists of Marburg, first discovered in 1967 in Marburg Germany, and ebola. Filovirus are long, worm-like virus particles that, in large groups, resemble a plate of noodles. As of April 2005, the Marburg virus is attracting widespread press attention for an outbreak in Angola. Beginning in October 2004 and continuing into 2005, the outbreak, which now appears to be coming under control, is the world's worst epidemic of any kind of hemorrhagic fever.
Laboratory diagnosis of pathogenic viruses
Detection and subsequent isolation of viruses from patients is a very specialised laboratory subject. Normally it requires the use of large facilities, expensive equipment, and highly trained specialists such as technicians, molecular biologists, and virologists. Often, this effort is undertaken by state and national governments and shared internationally through organizations like WHO.
Prevention and treatment of viral diseases
Because they use the machinery of their host cells to reproduce, viruses are difficult to kill. The most effective medical approaches to viral diseases, thus far, are vaccination to provide resistance to infection, and drugs that treat the symptoms of viral infections. Patients often ask for antibiotics, which are useless against viruses, and their misuse against viral infections is one of the causes of antibiotic resistance in bacteria. That said, sometimes, in life-threatening situations, the prudent course of action is to begin a course of antibiotic treatment while waiting for test results to determine whether the patient's symptoms are caused by a virus or a bacterial infection.
Etymology
Although the viruses were discovered by the Russian biologist Dmitry Ivanovsky in 1892, the name for them was coined later. The original word comes from the Latin virus referring to poison and other noxious things. Today it is used to describe the biological viruses discussed above and also as a metaphor for other parasitically-reproducing things, such as memes or computer viruses. The word virion or viron is used to refer to a single infective viral particle. The English plural form of virus is viruses. No reputable dictionary gives any other form, including such "reconstructed" Latin plural forms as viri (which actually means men). (No plural form appears in any extant Latin manuscript). (See plural of virus). The word does not have a traditional Latin plural because its original sense, poison is a mass noun like the English word furniture.
See also

- Horizontal gene transfer
- List of viruses
- Microbiology
- Prion
- Viral plaque
- Viroids
- Virology
- Virus classification
See also

- Wikipedia:WikiProject Viruses
- WikiSpecies:Virus
- Wiktionary:en:virus
References

- [http://www.virology.net/ All the Virology on the WWW]
- Radetsky, Peter (1994). The Invisible Invaders: Viruses and the Scientists Who Pursue Them. Backbay Books, ISBNs 0316732168 (hc), 0316732176 (pb).
- Theiler, Max and Downs, W. G. (1973). The Arthropod-Borne Viruses of Vertebrates: An Account of the Rockefeller Foundation Virus Program 1951-1970. Yale University Press.
-
- Chronic Active Human Herpesvirus-6 (HHV-6) Infection: A New Disease Paradigm - Joseph H. Brewer, M.D. http://www.plazamedicine.com/index.html
Numbered references
# Gelderblom, Hans R. (1996). [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.chapter.2252 41. Structure and Classification of Viruses] in [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed Medical Microbiology] 4th ed. Samuel Baron ed. The University of Texas Medical Branch at Galveston. ISBN 0963117211 Category:Virology als:Virus (Medizin) ko:바이러스 ms:Virus ja:ウイルス simple:Virus

Nucleic acid

A nucleic acid is a complex, high-molecular-weight biochemical macromolecule composed of nucleotide chains that convey genetic information. The most common nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Nucleic acids are found in all living cells and viruses. cells Nucleic acid, so called because of its prevalence in cellular nuclei, is the generic name of family of biopolymers. The monomers are called nucleotides, and each consists of three components: a nitrogenous heterocyclic base (either a purine or a pyrimidine), a pentose sugar, and a phosphate group. Different nucleic acid types differ in the specific sugar found in their chain (e.g. DNA or deoxyribonucleic acid contains 2-deoxyriboses). Also, the nitrogenous bases possible in the two nucleic acids are different: adenine, cytosine, and guanine are possible in both RNA and DNA, while thymine is possible only in DNA and uracil is possible only in RNA. The sugars and phosphates in nucleic acids are connected to each other in an alternating chain through shared oxygens (forming a phosphodiester functional group). Using the conventional nomenclature, the carbons to which the phosphate groups are attached are the 3' and the 5' carbons. The bases extend from a glycosidic linkage to the 1' carbon of the pentose ring. Nucleic acids may be single-stranded or double-stranded. A double-stranded nucleic acid consists of two single-stranded nucleic acids hydrogen-bonded together. RNA is usually single-stranded, but any given strand is likely to fold back upon itself to form double-helical regions. DNA is usually double-stranded, though some viruses have single-stranded DNA as their genome. Nucleic acids are primarily biology's means of storing and transmitting genetic information, though RNA is also capable of acting as an enzyme. Hydrophobic interaction of nucleic acids is poorly understood. Nucleic acids are insoluble in ethanol and insoluble in TCA.insoluble in cold water, hot water, dil HCl. Soluble in dil NaOH, alcohol and HCl There are various common sources of DNA and RNA:
- Calf thymus DNA provides large linear DNA. It contains many breaks.
- T4 phage DNA is circular and can be isolated intact.
- Teichoic acids present in the cell walls of some gram-positive bacteria present a chemical structure resembling nucleic acids without the nucleobases.

External links

- [http://www.sciencescape.org/bunq.html An Ambigraphic Nucleic Acid Notation] Category:Biochemicals Category:Molecular biology Category:Nitrogen metabolism ko:핵산 ja:核酸

Protein

. This protein was the first to have its structure solved by X-ray crystallography by Max Perutz and Sir John Cowdery Kendrew in 1958, which led to them receiving a Nobel Prize in Chemistry.]] A protein (in Greek πρωτεϊνη = first thread) is a complex, high-molecular-weight organic compound that consists of amino acids joined by peptide bonds. Proteins are essential to the structure and function of all living cells and viruses. Many proteins are enzymes or subunits of enzymes. Other proteins play structural or mechanical roles, such as those that form the struts and joints of the cytoskeleton, serving as biological scaffolds for the mechanical integrity and tissue signalling functions. Still more functions filled by proteins include immune response and the storage and transport of various ligands. In nutrition, proteins serve as the source of amino acids for organisms that do not synthesize those amino acids natively. Proteins are one of the classes of bio-macromolecules, alongside polysaccharides, lipids, and nucleic acids, that make up the primary constituents of living things. They are among the most actively-studied molecules in biochemistry, and were discovered by Jöns Jakob Berzelius in 1838. Almost all natural proteins are encoded by DNA. DNA is transcribed to yield RNA, which serves as a template for translation by ribosomes.

Properties of Protein

Structure

ribosome Main article: Protein structure Proteins are amino acid chains that fold into unique 3-dimensional structures. The shape into which a protein naturally folds is known as its native state, which is determined by its sequence of amino acids. Thus, proteins are their own polymers, with amino acids being the monomers. Biochemists refer to four distinct aspects of a protein's structure:
- Primary structure: the amino acid sequence
- Secondary structure: highly patterned sub-structures—alpha helix and beta sheet—or segments of chain that assume no stable shape. Secondary structures are locally defined, meaning that there can be many different secondary motifs present in one single protein molecule.
- Tertiary structure: the overall shape of a single protein molecule; the spatial relationship of the secondary structural motifs to one another
- Quaternary structure: the shape or structure that results from the union of more than one protein molecule, usually called subunit proteins subunits in this context, which function as part of the larger assembly or protein complex. In addition to these levels of structure, proteins may shift between several similar structures in performing their biological function. In the context of these functional rearrangements, these tertiary or quaternary structures are usually referred to as "conformations," and transitions between them are called conformational changes. Proteins are separated into two groups: Complete and Incomplete. Incomplete proteins are from plants and do not include all 20 amino acids. Complete proteins come from an animal and include all 20 amino acids. You get protein from mostly everything you eat, but whether all the amino acids are in them depends on what the substance is. The primary structure is held together by covalent peptide bonds, which are made during the process of translation. The secondary structures are held together by hydrogen bonds. The tertiary structure is held together primarily by hydrophobic interactions but hydrogen bonds, ionic interactions, and disulfide bonds are usually involved too. The process by which the higher structures form is called protein folding and is a consequence of the primary structure. The mechanism of protein folding is not entirely understood. Although any unique polypeptide may have more than one stable folded conformation, each conformation has its own biological activity and only one conformation is considered to be the active, or native conformation. The two ends of the amino acid chain are referred to as the carboxy terminus (C-terminus) and the amino terminus (N-terminus) based on the nature of the free group on each extremity.

Working with proteins

Proteins are sensitive to their environment. They may only be active in their native state, over a small pH range, and under solution conditions with a minimum quantity of electrolytes. A protein in its native state is often described as folded. A protein that is not in its native state is said to be denatured. Denatured proteins generally have no well-defined secondary structure. Many proteins denature and will not remain in solution in distilled water. One of the more striking discoveries of the 20th century was that the native and denatured states in many proteins were interconvertible, that by careful control of solution conditions (by for example, dialyzing away a denaturing chemical), a denatured protein could be converted to native form. The issue of how proteins arrive at their native state is an important area of biochemical study, called the study of protein folding. Through genetic engineering, researchers can alter the sequence and hence the structure, "targeting", susceptibility to regulation and other properties of a protein. The genetic sequences of different proteins may be spliced together to create "chimeric" proteins that possess properties of both. This form of tinkering represents one of the chief tools of cell and molecular biologists to change and to probe the workings of cells. Another area of protein research attempts to engineer proteins with entirely new properties or functions, a field known as protein engineering. Protein-protein interactions can be screened for using two-hybrid screening.

Protein regulation

Various molecules and ions are able to bind to specific sites on proteins. These sites are called binding sites. They exhibit chemical specificity. The particle that binds is called a ligand. The strength of ligand-protein binding is a property of the binding site known as affinity. Since proteins are involved in practically every function performed by a cell, the mechanisms for controlling these functions therefore depend on controlling protein activity. Regulation can involve a protein's shape or concentration. Some forms of regulation include:
- Allosteric modulation: When the binding of a ligand at one site on a protein affects the binding of ligand at another site.
- Covalent modulation: When the covalent modification of a protein affects the binding of a ligand or some other aspect of the protein's function.

Diversity

Proteins are generally large molecules, having molecular masses of up to 3,000,000 (the muscle protein titin has a single amino acid chain 27,000 subunits long). Such long chains of amino acids are almost universally referred to as proteins, but shorter strings of amino acids are referred to as "polypeptides," "peptides" or rarely, "oligopeptides". The dividing line is undefined, though "polypeptide" usually refers to an amino acid chain lacking tertiary structure which may be more likely to act as a hormone (like insulin), rather than as an enzyme (which depends on its defined tertiary structure for functionality). Proteins are generally classified as soluble, filamentous or membrane-associated (see integral membrane protein). Nearly all the biological catalysts known as enzymes are soluble proteins (with a recent notable execption being the discovery of ribozymes, RNA molecules with the catalytic properties of enzymes.) Antibodies, the basis of the adaptive immune system, are another example of soluble proteins. Membrane-associated proteins include exchangers and ion channels, which move their substrates from place to place but do not change them; receptors, which do not modify their substrates but may simply shift shape upon binding them. Filamentous proteins make up the cytoskeleton of cells and much of the structure of animals: examples include tubulin, actin, collagen and keratin, all of which are important components of skin, hair, and cartilage. Another special class of proteins consists of motor proteins such as myosin, kinesin, and dynein. These proteins are "molecular motors," generating physical force which can move organelles, cells, and entire muscles. muscle

Role of Protein

Functions

Proteins are involved in practically every function performed by a cell, including regulation of cellular functions such as signal transduction and metabolism. For example, protein catabolism requires enzymes termed proteases and other enzymes such as glycosidases.

Within Nutrition

Protein is an important macronutrient to the human diet, supplying the body's needs for nitrogen and amino acids, the building blocks of proteins. The exact amount of dietary protein needed to satisfy these requirements may vary widely depending on age, sex, level of physical activity, and medical condition, as well as the RDA specified by the state. The recommended intake of protein differs from country to country, but it is marginalised between 0.8 and 1.2g / kg b.w (Per kilogram of bodyweight), however , in more serious athletes, requiring strength, the figure is somewhat between 1.0 and 2.0g per kilogram of Body weight, which is referred to as the maximum protein intake:benefits ratio. Although proteins are found in all foods, be it only in small amounts , protein is still well concentrated in foods such as legumes, nuts, and dairy products, the majority of which are protein choices for vegetarians. Protein is the major component in the regulation, growth and differentation of muscles, tendons, enzymes, skin, hair, eyes, as well as a tremendous variety of other organs and processes. The quality of protein intake is particularly important because different proteins supply essential amino acids in different proportions. Given an adequate intake of nitrogen, the human body can manufacture 10 of the 18 amino acids from glucose. The remaining 8 amino acids (threonine, valine, tryptophan, isoleucine, leucine, lysine, phenylalanine, and methionine) cannot be manufactured by the body and must be acquired through supplementation. Thus, they are termed essential amino acids. For use within the body, the majority of protein taken from food consumed is converted by protein catabolism into ammonia which, due to its toxicity, must be converted to either urea or uric acid,or in some animals is excreted in urine. Proteins possessing equal proportions of all essential amino acids in relatively abundant quantities are often termed "complete", or "High-Quality" Proteins, which are generally obtained from animal proteins, such as meat , and are rated using PDCAAS (Protein Digestibility Corrected Amino Acid Score). Despite what the name suggests, quality proteins are not essential for good supplementation or nutrition within the average person, however, the difference between amino acids in plant and animal proteins is discernable, particularly for athletes or bodybuilders as plant proteins lack two major amino acids found in animal proteins; lysine within grains, and methionine within legumes, major benefactors to a major athlete's dietary regime. Neverthelss, in terms of quality, amino acids found in plant and animal extracts are identical. Protein deficiency can lead to symptoms such as fatigue, insulin resistance, hair loss, loss of hair pigment, loss of muscle mass , low body temperature, hormonal irregularities, as well as loss of skin elsaticity . Severe protein deficiency, encountered only in times of famine, is fatal, due to the lack of material for the body to facilitate as energy. It has been known that in some "wild diets", in which people lose mass amounts of weight in a short period of time are attributed to deficiencies in protein, and thus loss in muscle mass, and not fat, which is widely known as a dangerous practice, particularly because of the benefits of muscle mass over fat. Excessive protein intake has also been linked to several problems;
- overreaction within the immune system
- liver dysfunction due to increased toxic residues
- loss of bone density, frailty of bones due to increased acidity in the blood and foundering (foot problems) in horses. It is assumed by reasearchers on the field, that excessive intake of protein forced increased calcium excretion. If there is to be excessive intake of protein, it is thought that a regular intake of calcium would be able to stablilise, or even increase the uptake of calcium by the small intestine, which would be more beneficial in older women . Proteins are often progenitors in allergies and allergic reactions to certain foods. This is because the structure of each form of protein is slightly different; some may trigger a response from the immune system while others remain perfectly safe. Many people are allergic to casein, the protein in milk; gluten, the protein in wheat and other grains; the particular proteins found in peanuts; or those in shellfish or other seafoods. It is extremely unusual for the same person to adversely react to more than two different types of proteins, due to the diversity between protein or amino acid types.

History

The first mention of the word protein, which means of first rank, were from a letter sent by Jöns Jakob "Jinglehimer Schmidt" Berzelius to Gerhardus Johannes Mulder on 10. July 1838, where he wrote: :«Le nom protéine que je vous propose pour l’oxyde organique de la fibrine et de l’albumine, je voulais le dériver de πρωτειοξ, parce qu’il paraît être la substance primitive ou principale de la nutrition animale.» Translated as: :"The name protein that I propose for the organic oxide of fibrin and albumin, I wanted to derive from [the Greek word] πρωτειοξ, because it appears to be the primitive or principal substance of animal nutrition." Investigation of proteins and their properties had been going on since about 1800 when scientists were finding the first signs of this, at the time, unknown class of organic compounds.

References

# Kerstetter, J. E., O'Brien, K. O., Insogna, K. L. (2003) "[http://www.ajcn.org/cgi/content/full/78/3/584S Dietary protein, calcium metabolism, and skeletal homeostasis revisited]" . J Clin Endocrinol Metab Vol 78, p584S-592S. # Kerstetter, J. E., O'Brien, K. O., Caseria, D.M, Wall, D. E. & Insogna, K. L (2005) "The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women" . J Clin Endocrinol Metab (2005) Vol 90, p26-31, . # Devine, A., Dick, I. M,, Islam I. M., Dhaliwal, S. S. & Prince, R. L. (2005) "Protein consumption is an important predictor of lower limb bone mass in elderly women" . Am J Clin Nutr (2005) volume 81 pages 423-428, . # Jeukendrup, A. & Gleeson, M. (2004) Sport Nutrition - An Introduction to Energy Production and Performance USA : Human Kinetics # Bean, A. (2004) Sport Nutrition for Serious Athletes London : Routledge

External links

- [http://www.expasy.uniprot.org UniProt the Universal Protein Resource]
- [http://www.proteinatlas.org Human Protein Atlas]
- [http://www.ihop-net.org/UniPub/iHOP/ iHOP - Information Hyperlinked over Proteins]
- [http://www.biochemweb.org/proteins.shtml Proteins: Biogenesis to Degradation - The Virtual Library of Biochemistry and Cell Biology]
- [http://web.mit.edu/lms/www/ MIT's Laboratory for Protein Molecular Self-Assembly]
- [http://www.puramatrix.com/pubs Numerous publications on synthetic biomimetic protein-based biomaterials]
- [http://www.westernblotting.org Protein Research: Western Blot Protocols, Troubleshooting and Theory]
- [http://www.rcsb.org The Protein Databank: The single worldwide repository for the processing and distribution of 3-D biological macromolecular structure data.]
- [http://web.indstate.edu/thcme/mwking/amino-acid-metabolism.html Amino acid metabolism]
- [http://www.biochem.szote.u-szeged.hu/astrojan/protein2.htm Protein Images] Category:Molecular biology Category:Biochemistry Category:Nutrition zh-min-nan:Nn̄g-pe̍h-chit ko:단백질 ja:蛋白質 simple:Protein th:โปรตีน

Antigens

An antigen is a substance that stimulates an immune response, especially the production of antibodies. Antigens are usually proteins or polysaccharides, but can be any type of molecule, including small molecules (haptens) coupled to a protein (carrier).

Types of antigens

- Immunogen - Any substance that provokes the immune response when introduced into the body. An immunogen is always a macromolecule (protein, polysaccharide). Its ability to provoke the immune response depends on its foreignness to the host, molecular size, chemical composition and heterogeneity (e.g. different amino acids in a protein).
- Tolerogen - An antigen that invokes a specific immune non-responsiveness due to its molecular form. If its molecular form is changed, a tolerogen can become an immunogen.
- Allergen - An allergen is a substance that causes the allergic reaction. It can be ingested, inhaled, injected or comes into contact with skin. Cells present their antigens to the environment via a histocompatibility molecule. Depending on the antigen presented and the type of the histocompatibility molecule, several types of immune cells can become activated.

Origin of antigens

We can also classify antigens according to their origin.

Exogenous antigens

Exogenous antigens are antigens that have entered the body from the outside, for example by inhalation, ingestion, or injection. By endocytosis or phagocytosis, these antigens are taken into the antigen-presenting cells (APCs) and processed into fragments. APCs then present the fragments to T helper cells (CD4⁺) by the use of class II histocompatibility molecules on their surface. Some T cells are specific for the peptide:MHC complex. They become activated and start to secrete cytokines. Cytokines are substances that can activate cytotoxic T lymphocytes (CTL), antibody-secreting B cells, macrophages and other cells.

Endogenous antigens

Endogenous antigens are antigens that have been generated within the cell, as a result of normal cell metabolism, or because of viral or intracellular bacterial infection. The fragments are then presented on the cell surface in the complex with class I histocompatibility molecules. If activated cytotoxic CD8⁺ T cells recognize them, the T cells begin to secrete different toxins that cause the lysis or apoptosis of the infected cell. In order to keep the cytotoxic cells from killing cells just for presenting self-proteins, self-reactive T cells are deleted from the repertoire as a result of central tolerance (also known as negative selection which occurs in the thymus). Only those CTL that do not react to self-peptides that are presented in the thymus in the context of MHC class I molecules are allowed to enter the bloodstream. There is an exception to the exogenous/endogenous antigen paradigm, called cross-presentation.

Tumor antigens

Tumor antigens are those antigens that are presented by the MHC I molecules on the surface of tumor cells. These antigens can sometimes be presented only by tumor cells and never by the normal ones. In this case, they are called tumor-specific antigens and typically result from a tumor specific mutation. More common are antigens that are presented by tumor cells and normal cells, and they are called tumor-associated antigens. Cytotoxic T lymphocytes that recognized these antigens may be able to destroy the tumor cells before they proliferate or metastasize. Tumor antigens can also be on the surface of the tumor in the form of, for example, a mutated receptor, in which case they will be recognized by B cells.

Links

National Library of Medicine/Medline (National Insititute of Health) website http://www.nlm.nih.gov/medlineplus/ency/article/002224.htm

Alternative meanings

Antigen is also the name of Canadian indie band. (http://www.antigenmusic.com/music.html) Category:Immune system Category:Immunology ko:항원 ja:抗原

Antibodies

] An antibody is a protein used by the immune system to identify and neutralize foreign objects like bacteria and viruses. Each antibody recognizes a specific antigen unique to its target. Production of antibodies is referred to as the humoral immune system.

Definition

Immunoglobulins are glycoproteins in the immunoglobulin superfamily that function as antibodies. The terms antibody and immunoglobulin are often used interchangeably. They are found in the blood and tissue fluids, as well as many secretions. Structurally they are globulins (in the γ-region of protein electrophoresis). They are synthesized and secreted by plasma cells which are derived from the B cells of the immune system. B cells are activated upon binding to their specific antigen and differentiate into plasma cells. In some cases the interaction of the B cell with a T helper cell is also necessary.

Structure of the antibody

Immunoglobulins are heavy plasma proteins, often with added sugar chains (see glycosylation) on N-terminal (all antibodies) and occasionally O-terminal (IgA1 and IgD) amino acid residues. The basic unit of each antibody is a monomer. An antibody can be monomeric, dimeric, trimeric, tetrameric, pentameric etc. The monomer is a "Y"-shaped molecule that consists of two identical heavy chains and two identical light chains connected by disulfide bonds. There are five types of heavy chain: γ, δ, α, μ and ε. They define classes of immunoglobulins. Heavy chains α and γ have approximately 450 amino acids, while μ and ε have approximately 550 amino acids. Each heavy chain has a constant region, which is the same by all immunoglobulins of the same class, and a variable region which differs between immunoglobulins of different B cells, but is the same for all immunoglobulins produced by the same B cell. Heavy chains γ, α and δ have the constant region composed of three domains; the constant region of heavy chains μ and ε is composed of four domains. The variable domain of any heavy chain is composed of one domain. These domains are about 110 amino acids long. There are also some amino acids between constant domains. There are only two types of light chain: λ and κ. In humans they are similar, but only one type is present in each antibody. Each light chain has two successive domains: one constant and one variable domain. The approximate length of a light chain is from 211 to 217 amino acids. The monomer is composed of two heavy and two light chains. Together this gives six to eight constant domains and four variable domains. If it is cleaved with enzymes papain and pepsin, we get two Fab (fragment binding antigen) fragments and an Fc (fragment crystallizable) fragment. Each half of the forked end of the "Y" shaped monomer is called the Fab fragment. It is composed of one constant and one variable domain of each the heavy and the light chain, which together shape the antigen binding site at the amino terminal end of the monomer. The two variable domains bind the antigens they are specific for and that elicited their production. The ability to bind a wide variety of foreign antigens arises from events known as somatic recombination. This is when genes are selected (variable (V), diversity (D) and joining (J) for heavy chains, and only V and J for light chains) to form countless combinations. The main reason that the human immune system is capable of binding so many antigens is the variable region of the heavy chain. More specifically, it is the area where these V, D and J genes are found - otherwise known as the complementarity determining region 3 (CDR3). The Fc fragment is the stem of the "Y" and is composed from two heavy chains that each contribute two to three constant domains (depending on the class of the antibody). It binds to various cell receptors and complement proteins. In this way it mediates different physiological effects of antibodies (opsonization, cell lysis, mast cell, basophil and eosinophil degranulation and other processes). The variable regions of the heavy and light chains can be fused together to form a single chain variable fragment (scFv), which retains the original specificity of the parent immunoglobulin. A crude estimation of immunoglobulin levels can be made by protein electrophoresis. Here the plasma proteins are separated into albumin, alpha-globulins (1 and 2), beta-globulins (1 and 2) and gamma-globulins according to weight. Immunoglobulins are all in the gamma region. In some disease states (myeloma) a very high concentration of one particular immunoglobulin will show up as a monoclonal band.

Isotypes

According to differences in their heavy chain constant domains, immunoglobulins are grouped into five classes or isotypes: IgG, IgA, IgM, IgD, and IgE. (The isotypes are also defined with light chains, but they do not define classes, so they are often neglected.) Other immune cells partner with antibodies to eliminate pathogens depending on which IgG, IgA, IgM, IgD, and IgE constant binding domain receptors it can express on its surface. The antibodies that a single B lymphocyte produces can differ in their heavy chain and the B cell often expresses different classes of antibodies at the same time. However, they are identical in their specificity for antigen, conferred by their variable region. To achieve the large number of specificities the body needs to protect itself against many different foreign antigens, it must produce millions of B lymphoyctes. It is important to note that to produce such a diversity of antigen binding sites with a separate gene for each possible antigen, the immune system would require many more genes than exist in the genome. Instead, as Susumu Tonegawa showed in 1976, portions of the genome in B lymphocytes can recombine to form all the variation seen in the antibodies and more. Tonegawa won the Nobel Prize in Physiology or Medicine in 1987 for his discovery.

IgG

1987 IgG is a monomeric immunoglobulin, built of two heavy chains γ and two light chains. Each molecule has two antigen binding sites. This is the most abundant immunoglobulin and is approximately equally distributed in blood and in tissue liquids. This is the only isotype that can pass through the placenta, thereby providing protection to the fetus in its first weeks of life before its own immune system has developed. It can bind to many kinds of pathogens, for example viruses, bacteria, and fungi and protects the body against them by complement activation (classic pathway), opsonization for phagocytosis and neutralisation of their toxins. There are 4 subclasses: IgG1 (66%), IgG2 (23%), IgG3 (7%) and IgG4 (4%). IgG1,IgG2,IgG3 fix the complement but not IgG4.

IgA

IgA represent about 15 to 20% of immunoglobulins in the blood although it is primarily secreted across the mucosal tract into the stomach and intestines. It is also found in maternal milk, tears and saliva. This immunoglobulin helps to fight against pathogens that contact the body surface, ingested, or inhaled. It does not activate complement and opsonises only weakly. Its heavy chains are of the type α. It exists in two forms, IgA1 (90%) and IgA2 (10%) that differ in the structure. IgA1 is composed like other proteins, however in IgA2 the heavy and light chains are not linked with disulfide but with noncovalent bonds.Though IgA2 is less in serum,it accounts for major secretory antibody. The IgA found in secretions have a special form. They are dimeric molecules, linked by two additional chains. One of these is the J chain (from join), which is a polypeptide of molecular mass 1,5 kD, rich with cysteine and structurally completely different from other immunoglobulin chains. This chain is formed in the antibodies secreting cells. The dimeric form of IgA in the outer secretions has also a polypeptide of the same molecular mass (1,5 kD) that is called the secretory chain and is produced by the epithelial cells. It is also possible to find trimeric and even tetrameric IgA.

IgM

IgM forms polymers where multiple immunoglobulins are covalently linked together with disulfide bonds, usually as a pentamer or a hexamer. It has a large molecular mass of approximately 900 kD. The J chain is attached to most pentamers, while hexamers do not possess the J chain due to space constraints in the complex. Because each monomer has two antigen binding sites, an IgM has 10 of them, however it cannot bind 10 antigens at the same time because they hinder each other. Because it is a large molecule, it cannot diffuse well, and is found in the interstitium only in very low quantities. IgM is primarly found in serum, however of the J chain it is also important as a secretory immunoglobulin. Due to its polymeric nature, IgM possesses high avidity, and is particularly effective at complement activation. It is also a so-called "natural antibody": it is found in the serum without any evidence of prior contact with antigen. In germline cells, the gene segment encoding the μ constant region of the heavy chain is positioned first among other constant region gene segments. For this reason, IgM is the first immunoglobulin expressed by mature B cells.

IgD

IgD makes up about 1% in the plasma membranes in B-lymphocytes. It is monomeric with the δ heavy chain. While IgD's function is not yet completely understood, it is often coexpressed with IgM and is used as a marker of mature, naive B cells. It may also be involved in the differentiation of B cells into plasma and memory cells.

IgE

IgE is a monomeric immunoglobulin with the heavy chain ε. It contains a high proportion of carbohydrates. Its molecular mass is 190 kD. It can be found on the surface of the plasma membrane of basophils and mast cells of connective tissue. IgE plays a role in immediate hypersensitivity and the defense against parasites such as worms. The IgE antibodies are present also in outer excretions. They do not activate complement. Only IgE is heat labile.

Function

The antibodies have two primary functions:
- they bind antigens -- see below
- they combine with different immunoglobulin receptors specific for them and exert effector functions. These receptors are isotype specific, which gives a great flexibility to the immune system, because this enables that in different situations only certain immune mechanisms respond to antigens.

The humoral immune response

When a macrophage ingests a pathogen, it attaches parts of the pathogen's proteins to a class II MHC protein. This complex is moved to the outside of the cell membrane, where it can be recognized by a T lymphocyte, which compares it to similar structures on the cell membrane of a B lymphocyte. If it finds a matching pair, the T lymphocyte activates the B lymphocyte, which starts producing antibodies. A B lymphocyte can only produce antibodies against the structure it presents on its surface. Antibodies exist freely in the bloodstream or bound to cell membranes. They are part of the humoral immune system. Antibodies exist in clonal lines that are specific to only one antigen, e.g., a virus hull protein. In binding to such antigens, they can cause agglutination and precipitation of antibody-antigen products prime for phagocytosis by macrophages and other cells, block viral receptors and stimulate other immune responses such as the complement pathway. Antibodies that recognize viruses can block these directly by their sheer size. The virus will be unable to dock to a cell and infect it, hindered by the antibody. They can also agglutinate them so the phagocytes can capture them. Antibodies that recognize bacteria mark them for ingestion by macrophages. Together with the plasma component complement, antibodies can kill bacteria directly. They neutralize toxins by binding with them. It is important to note that antibodies cannot attack pathogens within cells, and certain viruses "hide" inside cells (as part of the lysogenic cycle) for long periods of time to avoid them. This is the reason for the chronic nature of many minor skin diseases (such as cold sores); any given outbreak is quickly suppressed by the immune system, but the infection is never truly eradicated because some cells retain viruses that will resume it later.

Medical applications

Detection of particular antibodies is a very common form of medical diagnostics. Serology depends on these methods. Autoimmune disorders can often be traced to antibodies that bind the body's own epitopes; many can be detected through blood tests. "Designed" monoclonal antibody therapy is already being employed in a number of diseases (including rheumatoid arthritis) and in some forms of cancer. Presently, many antibody-related therapies are undergoing extensive clinical trials for use in practice.

Biochemical applications

In biochemistry, antibodies are used for immunological identification of proteins, using the Western blot method. A similar technique is used in ELISPOT and ELISA assays, in which detection antibodies are used to detect cell secretions such as cytokines or antibodies. Antibodies are also used to separate proteins (and anything bound to them) from the other molecules in a cell lysate. These purified antibodies are often produced by injecting the antigen into a small mammal, such as a mouse or rabbit. Blood isolated from these animals contains polyclonal antibodies -- multiple antibodies that stick to the same antigen. The serum (=blood from which blood-clotting proteins and red-blood cells were removed), also known as the antiserum, because it now contains the desired antibodies, is commonly purified with Protein A/G purification or antigen affinity chromatography. If the lymphocytes that produce the antibodies can be isolated and immortalized, then a monoclonal antibody can be obtained.

References

- Rhoades, Rodney and Richard Pflanzer (2002). Human Physiology (4^th ed.). Brooks/Cole. ISBN 0534421741

External links

- [http://www.ihcworld.com/ihcmall Search and Find Antibodies]
- [http://www.immunoportal.com Antibody Search & Antibody Staining Protocols]
- [http://www.ihcworld.com/antibody_staining.htm Antibody Staining Protocol Database]
- [http://www.cellsalive.com/antibody.htm How Lymphocytes Produce Antibody]
- [http://www.lymphomation.org/tests-immunoglobulins.htm Lymphomation: Immunoglobulins]
- [http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0000016 Recombination and the Evolution of the Adaptive Immune System] Category:Immune system Category:Immunology Category:Glycoproteins ko:항체 ja:抗体

Endoplasmic reticulum

The endoplasmic reticulum or ER (endoplasmic means "within the cytoplasm," reticulum means "little net") is an organelle found in all eukaryotic cells. It is a continuation of the membrane. The ER modifies proteins, makes macromolecules, and transfers substances throughout the cell. Prokaryotic organisms do not have membrane-bound organelles, and thus do not have an ER (and other integral membrane proteins) as well as proteins that are to be secreted or "exocytosed" from the cell (e.g., digestive enzymes). In more depth, there are two different types of ER, Smooth ER (or agranular ER) and Rough ER (or granular ER). The Smooth ER synthesizes lipids, metabolizes carbohydrates and detoxifies drugs and poisons, whereas the Rough ER makes secretory proteins and produces membranes. The Smooth ER does not have ribosomes attached to it as the Rough ER does.

Functions

The endoplasmic reticulum serves many general functions, including the facilitation of protein folding, and the transport of proteins. Correct folding of newly made proteins is made possible by several ER proteins including: PDI, Hsp70 family, calnexin, calreticulin, and the peptidylpropyl isomerase family. Properly folded proteins are then transported from the ER to the Golgi complex for further maturation and sorting.

Transport of proteins

Secretory proteins are moved across the ER membrane. Proteins that are transported by the ER and from there throughout the cell are marked with an address tag that are called a signal sequence. The N-terminus (one end) of a polypeptide chain (e.g., a protein) contains a few amino acids that work as an address tag, which are removed when the polypeptide reaches its destination. Proteins that are destined for places outside the ER are packed into transport vesicles and moved along the cytoskeleton toward their destination. The ER is also part of a protein-sorting path

Other functions

- Insertion of proteins into the ER membrane. Integral proteins need to be inserted into the ER membrane after they are synthesized. Insertion into the ER membrane requires the correct topogenic sequences.
- Glycosylation. Glycosylation involves the attachment of oligosaccharides.
- Disulfide bond formation and rearrangement. Disulfide bonds stabilize the tertiary and quaternary structure of many proteins. Category:Organelles ja:小胞体

Cytoplasm

Cytoplasm is a homogeneous, generally clear jelly-like material that fills cells. The cytoplasm consists of cytosol and the cellular organelles, except the nucleus. The cytosol is made up of water, salts, organic molecules and many enzymes that catalyze reactions. The cytoplasm plays an important role in a cell, serving as a "molecular soup" in which the organelles are suspended and held together by a fatty membrane. It is found within the plasma membrane of a cell and surrounds the nuclear envelope and the cytoplasmic organelles.

Components of the cytoplasm

The aqueous component of the cytoplasm (making up 80 percent of it) is composed of ions and soluble macromolecules like enzymes, carbohydrates, different salts and proteins, as well as a great proportion of RNA. The cytoplasm's watery component is also known as hyaloplasm. The watery component can be more or less gel-like or liquid depending on the milieu's conditions and the activity phases of the cell. In the first case, it is named cytogel and is a viscid solid mass. In the second case, called cytosol, is a liquid in movement. In general, margin regions of the cell are gel-like and the cell's interior is liquid. The insoluble constituents of the cytoplasm are organelles (such as the mitochondria, the chloroplast, lysosomes, peroxysomes, ribosomes), several vacuoles, cytoskeletons as well as complex membrane structures (e.g. endoplasmic reticulums or the golgi apparatus). Image:Cytoplasm.jpg

Differences between animal and vegetal cytoplasm

While all cells possess a cytoplasm, cells from different biological domains can differ widely in the characteristics of their cytoplasms. In the animal kingdom, cytoplasm occupies nearly half the cell's volume while in plant cells, the cytoplasm occupies much less space because of the presences of vacuoles.

Function

The cytoplasm plays a mechanical role, that is, to maintain the shape and consistency of the cell, and to provide suspension to the organelles. It is also a storage place for chemical substances indispensable to life, which are involved in vital metabolic reactions, such as anaerobic glycolysis and protein synthesis. Category: Cell biology ms:Sitoplasma ja:細胞質

Nuclear membrane

The nuclear envelope refers to the double membrane of the nucleus that encloses genetic material in eukaryotic cells. It separates the contents of the nucleus (DNA in particular) from the cytosol. The space between the two membranes that make up the nuclear envelope is called the perinuclear space, and is usually about 20 - 100 nm wide. The outer membrane is continuous with the rough endoplasmic reticulum. Numerous nuclear pores are present on the nuclear envelope to facilitate and regulate the exchange of materials (for example, proteins and mRNA) between the nucleus and the cytoplasm. The inner membrane is erected upon the nuclear lamina, a network of intermediate filaments made of lamin, that plays a role in mitosis and meiosis. The nuclear envelope may also play a role in the disposition of chromatin inside the nucleus.

Disintegration during Mitosis in Metazoans

During prophase in mitosis, the chromotids begin replicating to form chromosomes, and the nuclear envelope begins to disintegrate. During metaphase, the nuclear envelope is completely disintegrated, and the chromosomes can be pulled apart as chromotins by the spindle fibers. Other Eukaryotes such as yeast undergo closed mitosis, where the chromosomes segregate within the nuclear envelope, which then buds as the two daughter cells divide. Synonyms: karyotheca, nuclear membrane, nucleolemma, perinuclear envelope ja:核膜

Influenza virus

Influenza (or as it is commonly known, the flu or the grippe) is a contagious disease of the lungs and upper airways, caused by an RNA virus of the orthomyxoviridae family. It rapidly spreads around the world in seasonal epidemics, imposing considerable economic burden, in the form of health care costs and lost productivity. Three influenza pandemics in the 20^th century each following a major genetic change in the virus, killed millions of people. Hybridization of a human Flu virus with the current H5N1 avian influenza has been identified as the most likely source of the next pandemic. The term influenza has its origins in 15th century Italy, where the cause of the disease was ascribed to unfavorable astrological influences. Evolution in medical thought led to its modification to "influenza di freddo" (meaning "influence of the cold"), which by the 18th century became the prevalent terminology in the English-speaking world as well. The latter term underlies the persistent, though unsubstantiated, popular belief that influenza is influenced or caused by exposure to the cold.

Types

There are three genera of the virus, identified by antigenic differences in their nucleoprotein and matrix protein:
- Influenza A viruses that infect mammals and birds (see also avian influenza)
- Influenza B viruses that infect only humans
- Influenza C viruses that infect only humans The A type of influenza virus is the type most likely to cause epidemics and pandemics. This is because the influenza A virus can undergo antigenic shift and present a new, immune target to susceptible people. Populations tend to have more resistance to influenza B and C, because they only undergo antigenic drift, and have more similarity with previous strains. Influenza A viruses can be further classified, based on the viral surface proteins hemagglutinin (HA or H) and neuraminidase (NA or N) that are essential to the virus' life cycle. Sixteen H subtypes and nine N subtypes have been identified for influenza A virus. Only one H subtype and one N subtype have been identified for influenza B virus. At present, the most common antigenic variants of influenza A virus are H1N1 and H3N2. (Yohannes et al., 2004) Yet further variation exists; thus, specific influenza strain isolates are identified by a standard nomenclature specifying virus type, geographical location where first isolated, year of isolation, sequential number of isolation, and HA and NA subtype (Yohannes et al 2004) Examples of the nomenclature are A/Moscow/10/99 (H3N2) and B/Hong Kong/330/2001. The term superflu is used to refer to a strain of flu that spreads unusually quickly, is unusually virulent, or for which the host is uncommonly unresponsive to treatment— the kinds of strains which cause epidemics or pandemics. There is no exact scientific definition of a superflu.

Genetics

Influenza A viruses contain their genome in eight separate linear segments of negative-sense RNA. Each segment contains a single gene, but some can be read twice at different starting points to create two distinct proteins. The segmented nature of the genome also allows for the exchange of entire genes between different viral strains when they cohabitate the same cell. The 8 genes are:
- HA gene encoding hemagglutinin which produces about 500 copies
- NA gene encoding neuraminidase which produces about 100 copies
- NP gene encoding nucleoprotein. Influenza A, B, and C are distinguished by their nucleoproteins
- M gene encoding two matrix proteins (the M1 and the M2) by using different reading frames from the same RNA segment
- NS gene encoding two distinct non-structural proteins by using different reading frames from the same RNA segment
- PA gene encoding an RNA polymerase
- PB1 gene encoding an RNA polymerase
- PB2 gene encoding an RNA polymerase The genome segments have common terminal sequences, and the ends of the RNA strands are partially complementary, allowing them to bond to each other by hydrogen bonds. After transcription from negative-sense to positive-sense RNA the +RNA strands get the cellular 5' cap added, allowing its processing as messenger RNA by ribosomes. The +RNA strands also serve for synthesis of -RNA strands for new virions. The RNA synthesis and its assembly with the nucleoprotein takes place in the cell nucleus, the synthesis of proteins takes place in the cytoplasm. The assembled virion cores leave the nucleus and migrate towards the cell membrane, with patches of viral transmembrane proteins (hemagglutinin, neuraminidase and M2 proteins) and an underlying layer of the M1 protein, and bud through these patches, releasing finished enveloped viruses into the extracellular fluid.

History

There were several serious outbreaks of influenza in the 20th century. The most famous (and the most lethal) was the so-called Spanish Flu pandemic (type A influenza, H1N1 strain), which lasted from 1918 to 1919, and is believed to have killed more people in total than World War I. While the war casualties accumulated over several years, the pandemic took most of its toll over a period of weeks. Lesser flu epidemics included the 1957 Asian Flu (type A, H2N2 strain) and the 1968 Hong Kong Flu (type A, H3N2 strain).

Known epidemics and pandemics - overview

In our times, some half a million people die of flu each year.
- 1918–20 – Spanish Flu, 500 million ill, 20 to 25 million died (pandemic)
- 1957–58 – Asian Flu, 1 to 1.5 million died (epidemic)
- 1969–69 – Hong Kong Flu, 3/4 to 1 million died (epidemic) Although there were scares in New Jersey in 1976 (the Swine Flu), worldwide in 1977 (the Russian Flu), and in Hong Kong (as well as in other Asian countries, namely continental China, as became known later) in 1997 (Avian influenza), there have been no major pandemics subsequent to the 1968 infection. Increased immunity from antibodies, and the development of flu vaccines have limited the spread of the virus, and so far prevented any further pandemics.

Symptoms

The virus attacks the respiratory tract, is transmitted from person to person by saliva droplets expelled by coughing, and causes the following [http://www.arrestflu.com/symptoms-of-bird-flu.html symptoms]:
- Fever
- Headache
- Fatigue/Sore joints (can be extreme)
- Dry cough
- Sore throat
- Nasal congestion
- Sneezing
- Irritated eyes
- Body aches
- Extreme coldness Influenza's effects are much more severe, and last longer than those of the "cold". Recovery takes about one to two weeks. Influenza can be deadly, especially for the weak, old or chronically ill. Some flu pandemics have killed millions of people. Most people who get influenza will recover in one to two weeks, but others will develop life-threatening complications (such as pneumonia). Millions of people in the United States (about 10% to 20% of U.S. residents) are infected with influenza each year. An average of about 36,000 people per year in the United States die from influenza, and 114,000 per year are admitted to a hospital as a result of influenza. It has been reported that 2 million people die from influenza complications in the world each year. Even healthy people can be affected, and serious problems from influenza can happen at any age. People age 65 years and older, people of any age with chronic medical conditions, and very young children are more likely to get complications from influenza. Pneumonia, bronchitis, sinus, and ear infections are four examples of such complications. The flu can make chronic health problems worse. For example, people with asthma may experience asthma attacks while they have the flu, and people with chronic congestive heart failure may have a worsening of this condition, that is triggered by the flu.
Variability
Influenza is an extremely variable disease; similar viruses are found in pigs and domestic fowl. In areas where there are high concentrations of humans, pigs and birds in close proximity, such as parts of Asia, simultaneous infections across species enable genetic material to be exchanged between the various strains of flu. This appears to be the principal method by which new infectious strains arise. It is believed that sooner or later, a recombination may occur to produce a strain as lethal as the 1918 virus. In late 1997, a new strain of avian influenza (also known as bird flu) called H5N1 originating from chickens infected 18 people in Hong Kong, of whom 6 died. This strain did not appear to be readily transmissible from human to human, but such a high mortality rate, and the possibility of a further recombination to make it more infectious, meant that the risk was considered so great that all domestic poultry in Hong Kong was slaughtered. Avian influenza transmissible to humans resurfaced in January 2004 in Cambodia, Vietnam, and Thailand.
Flu season
Influenza reaches peak prevalence in winter, and because the Northern and Southern Hemisphere have winter at different times of the year, there are actually two flu seasons each year. Hope-Simpson (1981) observed that influenza outbreaks are globally ubiquitous, and consistently occur six months following the time of maximum solar radiation in an area. Therefore, the World Health Organization makes two vaccine formulations every year; one for the Northern, and one for the Southern Hemisphere. While most influenza outbreaks in the Northern Hemisphere tend to peak in January or February, not all do. For example, the influenza pandemic of 1918 and 1919 reached peak virulence during late spring and summer worldwide, and not until October in the US. It remains unclear why outbreaks of the flu occur seasonally rather than uniformly throughout the year. One possible explanation is that, because people are indoors more often during the winter, they are in close contact more often, and this is enough to trigger the outbreak. Another is that the cold weakens the immune system; however, the virus is contracted in a warm indoor environment in which it can thrive.
Prevention
It is possible and in many cases recommended to get vaccinated against influenza with a flu vaccine. However, due to the high mutability of the virus, a particular flu vaccine formulation usually only works for about a year. The World Health Organization co-ordinates the contents of the vaccine each year, to contain the most likely strains of the virus which probably will attack the next year. The flu vaccine is usually recommended for anyone in a high-risk group, who would be likely to suffer complications from influenza. Flu vaccine is available as nasal spray vaccine (recommended for all healthy people ages 5 to 49) and as injectable vaccine.
Treatment
Antiviral treatments that have proven effective in influenza are amantadine, rimantadine, zanamivir, oseltamivir and ribavirin. As most of these substances are expensive, various healthcare organisations and insurers only support their use where this would make a significant difference, e.g. in the elderly. Worryingly, investigators at the CDC in Atlanta found high rates of resistance to adamantane derivatives (amantadine, rimantadine) in the H3N2 strain of influenza A: China 74%, Hong Kong (70%), Taiwan (23%), South Korea (15%) (Bright et al 2005). The overall resistance rate in North America was 4%. The enormous rate of resistance in China is believed to be due to the ready availability of amantadine in over-the-counter cold remedies. A trademarked elderberry extract may aid in shortening the duration of an episode of influenza once contracted, though it has no notable preventive effects (Zakay-Rones et al 1995).
Avian influenza
The natural host for influenza virus is aquatic birds. Pandemic influenza often occurs when an avian-adapted virus infects a porcine host, which can be infected by human and avian varieties of influenza A virus. The virus may then recombine within the pig, to form a genetically new virus which is able to infect humans and be transmitted from person to person. The current avian flu threat (2005) is due to the H5N1 virus. This virus is currently still avian-adapted and cannot be transmitted from person to person, though it seems to be able to infect humans and cause mortality. It is thought likely, however, that the virus will eventually become adapted and able to spread from person to person by recombining with a human-adapted form either in a human or pig host. If this happens, a pandemic may be unavoidable, since there will be very little immunity to this genetically new virus, and international travel coupled with densely populated cities will spread the virus rapidly. Currently, governments are stockpiling anti-viral drugs such as Tamiflu, which can reduce the effects of the virus. It is difficult to design a vaccine for the virus until it has recombined into a human adapted form, but if a pandemic does occur a vaccine will be required urgently. Although the threat is very real, it is impossible to say when or if the virus will become human-adapted.
References

-
- Hope-Simpson RE (1981). The role of season in the epidemiology of influenza. J Hyg (Lond) 86 (1), 35-47. PMID 7462597
- Yohannes K, Roche P, Hampson A, Miller M, Spencer J (2004). Annual report of the National Influenza Surveillance Scheme, 2003. Commun Dis Intell 28 (2), 160-8. PMID 15460951
- Zakay-Rones Z, Varsano N, Zlotnik M, Manor O, Regev L, Schlesinger M, Mumcuoglu M. Inhibition of several strains of influenza virus in vitro and reduction of symptoms by an elderberry extract (Sambucus nigra L.) during an outbreak of influenza B Panama. J Altern Complement Med. 1995 Winter;1(4):361-9. PMID 9395631.
External links

- Some of this article was originally from the public domain CDC publication http://www.cdc.gov/
- [http://www.checkflu.com/glossary/a-terms.html Glossary of Flu and Influenza Terms]
- [http://www.pandemic-news.info Global Pandemic News] the international news site with 24 X 7 live news feeds (very popular site, international coverage and resources).
- [http://www.nhsdirect.nhs.uk/en.aspx?articleId=163§ionId=1725 NHS Direct Health encyclopedia entry]
- zh-min-nan:Liû-hêng-sèng kám-mō· ja:インフルエンザ

Hepatitis

Hepatitis is a gastroenterological disease, featuring inflammation of the liver. The clinical signs and prognosis, as well as the therapy, depend on the cause.

Signs and symptoms

Hepatitis is characterised by fatigue, malaise, joint aches, abdominal pain, vomiting 2-3 times per day for the first 5 days, loss of appetite, dark urine, fever, hepatomegaly (enlarged liver) and jaundice (icterus). Some chronic forms of hepatitis show very few of these signs and only present when the longstanding inflammation has led to the replacement of liver cells by connective tissue; the result is cirrhosis. Certain liver function tests can also indicate hepatitis.

Types of hepatitis

Viral

Most cases of acute hepatitis are due to viral infections:
- Hepatitis A
- Hepatitis B
- Hepatitis C
- D-agent (requires presence of the hepatitis B virus)
- Hepatitis E
- Hepatitis F (discredited)
- Hepatitis G :Please see the respective articles for more detailed information Hepatitis A is an enterovirus transmitted by the orofecal route, such as contaminated food. It causes an acute form of hepatitis and does not have a chronic stage. The patient's immune system makes antibodies against Hepatitis A that confer immunity against future infection. People with Hepatitis A are usually advised to rest, stay hydrated and avoid alcohol. A vaccine is available that will prevent infection from hepatitis A for life. Hepatitis B causes both acute and chronic hepatitis in some patients who are unable to eliminate the virus. Identified methods of transmission include blood (blood transfusion, now rare), tattoos (both amateur and professionally done), sexually or vertically (from mother to her unborn child). However, in about half of cases the source of infection cannot be determined. Blood contact can occur by sharing syringes in intravenous drug use, shaving accessories such as razor blades, or touching wounds on infected persons. Needle-exchange programmes have been created in many countries as a form of prevention. In the United States, 95% of patients clear their infection and develop antibodies against Hepatitis B virus. 5% of patients do not clear the infection and develop chronic infection; only these people are at risk of long term complications of Hepatitis B. Patients with chronic hepatitis B have antibodies against Hepatitis B, but these antibodies are not enough to clear the infection that establishes itself in the DNA of the affected liver cells. The continued production of virus combined with antibodies is a likely cause of immune complex disease seen in these patients. A vaccine is available that will prevent infection from hepatitis B for life. Hepatitis B infections result in 500,000 to 1,200,000 deaths per year worldwide due to the complications of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Hepatitis B is endemic in a number of (mainly South-East Asian) countries, making cirrhosis and hepatocellular carcinoma big killers. There are three, FDA-approved treatment options available for persons with a chronic hepatitis B infection: alpha-interferon, adefovir and lamivudine. In about 45% of persons on treatment achieve a sustained repsonse. Hepatitis C (originally "non-A non-B hepatitis") is probably not transmitted sexually but only by blood contact. It leads to a chronic form of hepatitis, culminating in cirrhosis. It can remain asymptomatic for 10-20 years. No vaccine is available for hepatitis C. Patients with hepatitis C are prone to severe hepatitis if they contract either hepatitis A or B, so all hepatitis C patients should be immunized against Hepatitis A and Hepatitis B if they are not already immune. Two other hepatitis viruses are known, hepatitis D and E. The D agent, an