In biology, histones are alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, playing a role in gene regulation. Without histones, the unwound DNA in chromosomes would be long. For example, each human diploid cell has about 1.8 meters of DNA. When the diploid cells are duplicated and condensed during mitosis, the result is about 120 micrometers of chromosomes. Five major families of histones exist: H1/H5, H2A, H2B, H3, H4. Histones H2A, H2B, H3 and H4 are known as the core histones, while histones H1/H5 are known as the linker histones; the core histones all exist as dimers, which are similar in that they all possess the histone fold domain: three alpha helices linked by two loops. It is this helical structure that allows for interaction between distinct dimers in a head-tail fashion; the resulting four distinct dimers come together to form one octameric nucleosome core 63 Angstroms in diameter.
Around 146 base pairs of DNA wrap around this core particle 1.65 times in a left-handed super-helical turn to give a particle of around 100 Angstroms across. The linker histone H1 binds the nucleosome at the entry and exit sites of the DNA, thus locking the DNA into place and allowing the formation of higher order structure; the most basic such formation is the 10 nm fiber or beads on a string conformation. This involves the wrapping of DNA around nucleosomes with 50 base pairs of DNA separating each pair of nucleosomes. Higher-order structures include the 30 nm fiber and 100 nm fiber, these being the structures found in normal cells. During mitosis and meiosis, the condensed chromosomes are assembled through interactions between nucleosomes and other regulatory proteins. Histones are subdivided into canonical replication-dependent histones that are expressed during the S-phase of cell cycle and replication-independent histone variants, expressed during the whole cell cycle. In animals, genes encoding canonical histones are clustered along the chromosome, lack introns and use a stem loop structure at the 3’ end instead of a polyA tail.
Genes encoding histone variants are not clustered, have introns and their mRNAs are regulated with polyA tails. Complex multicellular organisms have a higher number of histone variants providing a variety of different functions. Recent data are accumulating about the roles of diverse histone variants highlighting the functional links between variants and the delicate regulation of organism development. Histone variants from different organisms, their classification and variant specific features can be found in "HistoneDB 2.0 - Variants" database. The following is a list of human histone proteins: The nucleosome core is formed of two H2A-H2B dimers and a H3-H4 tetramer, forming two nearly symmetrical halves by tertiary structure; the H2A-H2B dimers and H3-H4 tetramer show pseudodyad symmetry. The 4'core' histones are similar in structure and are conserved through evolution, all featuring a'helix turn helix turn helix' motif, they share the feature of long'tails' on one end of the amino acid structure - this being the location of post-translational modification.
Archaeal histone only contains a H3-H4 like dimeric structure made out of the same protein. Such dimeric structures can stack into a tall superhelix onto which DNA coils in a manner similar to nucleosome spools. Only some archaeal histones have tails, it has been proposed that histone proteins are evolutionarily related to the helical part of the extended AAA+ ATPase domain, the C-domain, to the N-terminal substrate recognition domain of Clp/Hsp100 proteins. Despite the differences in their topology, these three folds share a homologous helix-strand-helix motif. Using an electron paramagnetic resonance spin-labeling technique, British researchers measured the distances between the spools around which eukaryotic cells wind their DNA, they determined the spacings range from 59 to 70 Å. In all, histones make five types of interactions with DNA: Helix-dipoles form alpha-helixes in H2B, H3, H4 cause a net positive charge to accumulate at the point of interaction with negatively charged phosphate groups on DNA Hydrogen bonds between the DNA backbone and the amide group on the main chain of histone proteins Nonpolar interactions between the histone and deoxyribose sugars on DNA Salt bridges and hydrogen bonds between side chains of basic amino acids and phosphate oxygens on DNA Non-specific minor groove insertions of the H3 and H2B N-terminal tails into two minor grooves each on the DNA moleculeThe basic nature of histones, aside from facilitating DNA-histone interactions, contributes to their water solubility.
Histones are subject to post translational modification by enzymes on their N-terminal tails, but in their globular domains. Such modifications include methylation, acetylation, phosphorylation, SUMOylation, ADP-ribosylation; this affects their function of gene regulation. In general, genes that are active have less bound histone, while inactive genes are associated with histones during interphase, it a
A cilium is an organelle found on eukaryotic cells and are slender protuberances that project from the much larger cell body. There are two types of cilia: motile cilia and non-motile, or primary, which serve as sensory organelles. In eukaryotes, motile cilia and flagella together make up a group of organelles known as undulipodia. Eukaryotic cilia are structurally identical to eukaryotic flagella, although distinctions are sometimes made according to function and/or length. Biologists have various ideas about. Cilia can be divided into motile forms. In animals, primary cilia are found on nearly every cell. In comparison to motile cilia, non-motile cilia occur one per cell. In addition, examples of specialized primary cilia can be found in human sensory organs such as the eye and the nose: The outer segment of the rod photoreceptor cell in the human eye is connected to its cell body with a specialized non-motile cilium; the dendritic knob of the olfactory neuron, where the odorant receptors are located contains non-motile cilia.
Although the primary cilium was discovered in 1898, it was ignored for a century. Only has great progress been made in understanding the function of the primary cilium; until the 1990s, the prevailing view of the primary cilium was that it was a vestigial organelle without important function. Recent findings regarding its physiological roles in chemical sensation, signal transduction, control of cell growth, have led scientists to acknowledge its importance in cell function, with the discovery of its role in diseases not recognized to involve the dysgenesis and dysfunction of cilia, such as polycystic kidney disease, congenital heart disease, an emerging group of genetic ciliopathies, it is known that the cilium must be disassembled before mitosis can occur. However, the mechanisms that control this process are still unknown; the primary cilium is now known to play an important role in the function of many human organs. The current scientific understanding of primary cilia views them as "sensory cellular antennae that coordinate a large number of cellular signaling pathways, sometimes coupling the signaling to ciliary motility or alternatively to cell division and differentiation.".
The primary non-motile cilia is divided into subdomains. The entire structure is enclosed by a plasma membrane continuous with the plasma membrane of the cell; the basal body, where the cilia originates, is located within the ciliary pocket. The cilium membrane and the basal body microtubules are connected by transition fibers. Vesicles carrying molecules for the cilia dock at the transition fibers; the transition fibers form a transition zone where entry and exit of molecules is regulated to and from the cilia. Molecules can move to the tip of the cilia with the aid of anterograde IFT particles and the kinesin-2 motor. Molecules can use retrograde IFT particles and the cytoplasmic dynein motor to move toward the basal body; some of the signaling with these cilia occur through ligand binding such as Hedgehog signaling. Other forms of signaling include G-coupled receptors including the somatostatin receptor 3 in neuronal cells. Larger eukaryotes, such as mammals, have motile cilia as well. Motile cilia are present on a cell's surface in large numbers and beat in coordinated waves.
In humans, for example, motile cilia are found in the lining of the trachea, where they sweep mucus and dirt out of the lungs. In female mammals, the beating of cilia in the Fallopian tubes moves the ovum from the ovary to the uterus; the functioning of motile cilia is dependent on the maintenance of optimal levels of fluid bathing the cilia. Epithelial sodium channels ENaC that are expressed along the entire length of cilia serve as sensors that regulate fluid level surrounding the cilia. Ciliates are microscopic organisms that possess motile cilia and use them for either locomotion or to move liquid over their surface. Inside cilia and flagella is a microtubule-based cytoskeleton called the axoneme; the axoneme of primary cilia has a ring of nine outer microtubule doublets, the axoneme of a motile cilium has two central microtubule singlets in addition to the nine outer doublets. The axonemal cytoskeleton acts as a scaffolding for various protein complexes and provides binding sites for molecular motor proteins such as kinesin II, that help carry proteins up and down the microtubules.
On the outside of cilia is a membrane like the plasma membrane, but compositionally distinct due to a blocking ring around the base, distinct in its population of receptors and other integral proteins. The ciliary rootlet is a cytoskeleton-like structure that originates from the basal body at the proximal end of a cilium, it extends proximally toward the cell nucleus. Rootlets are 80-100 nm in diameter and contain cross striae distributed at regular intervals of 55-70 nm. According to the Gene Ontology, the following proteins localize to the ciliary rootlet: amyloid precursor protein, rootletin and presenilins. Though they have been given different names, motile cilia and flagella have nearly identical structures and have the same purpose: motion; the movement of the appendage can be described as a wave. The wave tends to originate from the cilium base and can be described in terms of frequency and wave length; the beating motion is creat
A peroxisome is a type of organelle known as a microbody, found in all eukaryotic cells. They are involved in catabolism of long chain fatty acids, branched chain fatty acids, D-amino acids, polyamines, reduction of reactive oxygen species – hydrogen peroxide – and biosynthesis of plasmalogens, i.e. ether phospholipids critical for the normal function of mammalian brains and lungs. They contain 10% of the total activity of two enzymes in the pentose phosphate pathway, important for energy metabolism, it is vigorously debated whether peroxisomes are involved in isoprenoid and cholesterol synthesis in animals. Other known peroxisomal functions include the glyoxylate cycle in germinating seeds, photorespiration in leaves, glycolysis in trypanosomes, methanol and/or amine oxidation and assimilation in some yeasts. Peroxisomes were identified as organelles by the Belgian cytologist Christian de Duve in 1967 after they had been first described by a Swedish doctoral student, J. Rhodin in 1954. A major function of the peroxisome is the breakdown of long chain fatty acids through beta oxidation.
In animal cells, the long fatty acids are converted to medium chain fatty acids, which are subsequently shuttled to mitochondria where they are broken down to carbon dioxide and water. In yeast and plant cells, this process is carried out in peroxisomes; the first reactions in the formation of plasmalogen in animal cells occur in peroxisomes. Plasmalogen is the most abundant phospholipid in myelin. Deficiency of plasmalogens causes profound abnormalities in the myelination of nerve cells, one reason why many peroxisomal disorders affect the nervous system. Peroxisomes play a role in the production of bile acids important for the absorption of fats and fat-soluble vitamins, such as vitamins A and K. Skin disorders are features of genetic disorders affecting peroxisome function as a result. Peroxisomes contain oxidative enzymes, such as uric acid oxidase; however the last enzyme is absent in humans, explaining the disease known as gout, caused by the accumulation of uric acid. Certain enzymes within the peroxisome, by using molecular oxygen, remove hydrogen atoms from specific organic substrates, in an oxidative reaction, producing hydrogen peroxide: R H 2 + O 2 → R + H 2 O 2 Catalase, another peroxisomal enzyme, uses this H2O2 to oxidize other substrates, including phenols, formic acid and alcohol, by means of the peroxidation reaction: H 2 O 2 + R ′ H 2 → R ′ + 2 H 2 O, thus eliminating the poisonous hydrogen peroxide in the process.
This reaction is important in liver and kidney cells, where the peroxisomes detoxify various toxic substances that enter the blood. About 25% of the ethanol alcohol humans drink is oxidized to acetaldehyde in this way. In addition, when excess H2O2 accumulates in the cell, catalase converts it to H2O through this reaction: 2 H 2 O 2 → 2 H 2 O + O 2 In higher plants, peroxisomes contain a complex battery of antioxidative enzymes such as superoxide dismutase, the components of the ascorbate-glutathione cycle, the NADP-dehydrogenases of the pentose-phosphate pathway, it has been demonstrated that peroxisomes generate nitric oxide radicals. The peroxisome of plant cells is polarised. Infection causes a glucosinolate molecule to play an antifungal role to be made and delivered to the outside of the cell through the action of the peroxisomal proteins. Peroxisomes can be replicate by fission. Peroxisome matrix proteins are translated in the cytoplasm prior to import. Specific amino acid sequences at the C-terminus or N-terminus of peroxisomal matrix proteins signals them to be imported into the organelle.
There are at least 32 known peroxisomal proteins, called peroxins, which participate in the process of peroxisome assembly. Proteins do not have to unfold to be imported into the peroxisome; the protein receptors, the peroxins PEX5 and PEX7, accompany their cargoes all the way into the peroxisome where they release the cargo and return to the cytosol – a step named recycling. A model describing the import cycle is referred to as the extended shuttle mechanism. There is now evidence. Ubiquitination appears to be crucial for the export of PEX5 from the peroxisome, to the cytosol. Peroxisomal disorders are a class of medical conditions that affect the human nervous system as well as many other organ systems. Two common examples are X-linked peroxisome biogenesis disorders. PEX genes encode the protein machinery required for proper perox
Dynein is a family of cytoskeletal motor proteins that move along microtubules in cells. They convert. Dynein transports various cellular cargos, provides forces and displacements important in mitosis, drives the beat of eukaryotic cilia and flagella. All of these functions rely on dynein's ability to move towards the minus-end of the microtubules, known as retrograde transport, they are called "minus-end directed motors". In contrast, kinesin motor proteins move toward the microtubules' plus end. Dyneins can be divided into two groups: cytoplasmic dyneins and axonemal dyneins, which are called ciliary or flagellar dyneins. Axonemal heavy chain: DNAH1, DNAH2, DNAH3, DNAH5, DNAH6, DNAH7, DNAH8, DNAH9, DNAH10, DNAH11, DNAH12, DNAH13, DNAH14, DNAH17 intermediate chain: DNAI1, DNAI2 light intermediate chain: DNALI1 light chain: DNAL1, DNAL4 cytoplasmic heavy chain: DYNC1H1, DYNC2H1 intermediate chain: DYNC1I1, DYNC1I2 light intermediate chain: DYNC1LI1, DYNC1LI2, DYNC2LI1 light chain: DYNLL1, DYNLL2, DYNLRB1, DYNLRB2, DYNLT1, DYNLT3 Axonemal dynein causes sliding of microtubules in the axonemes of cilia and flagella and is found only in cells that have those structures.
Cytoplasmic dynein, found in all animal cells and plant cells as well, performs functions necessary for cell survival such as organelle transport and centrosome assembly. Cytoplasmic dynein moves processively along the microtubule. Cytoplasmic dynein helps to position the Golgi other organelles in the cell, it helps transport cargo needed for cell function such as vesicles made by the endoplasmic reticulum and lysosomes. Dynein is involved in the movement of chromosomes and positioning the mitotic spindles for cell division. Dynein carries organelles and microtubule fragments along the axons of neurons toward the cell body in a process called retrograde axoplasmic transport. Cytoplasmic dynein positions the spindle at the site of cytokinesis by anchoring to the cell cortex and pulling on astral microtubules emanating from centrosome. Budding yeast have been a powerful model organism to study this process and has shown that dynein is targeted to plus ends of astral microtubules and delivered to the cell cortex via an offloading mechanism.
Dynein and Kinesin can both be exploited by viruses to mediate the viral replication process. Many viruses use the microtubule transport system to transport nucleic acid/protein cores to intracellular replication sites after invasion past the cell membrane. Not much is known about virus' motor-specific binding sites, but it is known that some viruses contain proline-rich sequences which, when removed, reduces dynactin binding, axon transport, neuroinvasion in vivo; this suggests. Each molecule of the dynein motor is a complex protein assembly composed of many smaller polypeptide subunits. Cytoplasmic and axonemal dynein contain some of the same components, but they contain some unique subunits. Cytoplasmic dynein, which has a molecular mass of about 1.5 megadaltons, is a dimer of dimers, containing twelve polypeptide subunits: two identical "heavy chains", 520 kDa in mass, which contain the ATPase activity and are thus responsible for generating movement along the microtubule. The force-generating ATPase activity of each dynein heavy chain is located in its large doughnut-shaped "head", related to other AAA proteins, while two projections from the head connect it to other cytoplasmic structures.
One projection, the coiled-coil stalk, binds to and "walks" along the surface of the microtubule via a repeated cycle of detachment and reattachment. The other projection, the extended tail, binds to the light intermediate and light chain subunits which attach dynein to its cargo; the alternating activity of the paired heavy chains in the complete cytoplasmic dynein motor enables a single dynein molecule to transport its cargo by "walking" a considerable distance along a microtubule without becoming detached. Yeast dynein can walk along microtubules without detaching, however in metazoans, cytoplasmic dynein must be activated by the binding of dynactin, another multisubunit protein, essential for mitosis, a cargo adaptor; the tri-complex, which includes dynein, dynactin and a cargo adaptor, is ultra-processive and can walk long distances without detaching in order to reach the cargo's intracellular destination. Cargo adaptors identified thus far include Hook3, FIP3 and Spindly; the light intermediate chain, a member of the Ras superfamily, mediates the attachment of several cargo adaptors to the dynein motor.
The other tail subunits may help facilitate this interaction as evidenced in a low resolution structure of dynein-dynactin-BicD2. One major form of motor regulation within cells for dynein is dynactin, it may be required for all cytoplasmic dynein functions. It is the best studied dynein partner. Dynactin is a protein that aids in intracellular transport throughout the cell by linking to cytoplasmic dynein. Dynactin can function as a scaffold for other proteins to bind to, it functions as a recruiting factor that localizes dynein to where it should be. There is some evidence suggesting that it may regulate kinesin-2; the dynactin complex is composed of more than 20 subunits, of which p150 is the
Homologous recombination is a type of genetic recombination in which nucleotide sequences are exchanged between two similar or identical molecules of DNA. It is most used by cells to repair harmful breaks that occur on both strands of DNA, known as double-strand breaks. Homologous recombination produces new combinations of DNA sequences during meiosis, the process by which eukaryotes make gamete cells, like sperm and egg cells in animals; these new combinations of DNA represent genetic variation in offspring, which in turn enables populations to adapt during the course of evolution. Homologous recombination is used in horizontal gene transfer to exchange genetic material between different strains and species of bacteria and viruses. Although homologous recombination varies among different organisms and cell types, most forms involve the same basic steps. After a double-strand break occurs, sections of DNA around the 5' ends of the break are cut away in a process called resection. In the strand invasion step that follows, an overhanging 3' end of the broken DNA molecule "invades" a similar or identical DNA molecule, not broken.
After strand invasion, the further sequence of events may follow either of two main pathways discussed below. Homologous recombination that occurs during DNA repair tends to result in non-crossover products, in effect restoring the damaged DNA molecule as it existed before the double-strand break. Homologous recombination is conserved across all three domains of life as well as viruses, suggesting that it is a nearly universal biological mechanism; the discovery of genes for homologous recombination in protists—a diverse group of eukaryotic microorganisms—has been interpreted as evidence that meiosis emerged early in the evolution of eukaryotes. Since their dysfunction has been associated with increased susceptibility to several types of cancer, the proteins that facilitate homologous recombination are topics of active research. Homologous recombination is used in gene targeting, a technique for introducing genetic changes into target organisms. For their development of this technique, Mario Capecchi, Martin Evans and Oliver Smithies were awarded the 2007 Nobel Prize for Physiology or Medicine.
Researching the plasmid-induced DSB, using γ-irradiation in the 1970s-1980s, led to experiments using endonucleases to cut chromosomes for genetic engineering of mammalian cells, where nonhomologous recombination is more frequent than in yeast. In the early 1900s, William Bateson and Reginald Punnett found an exception to one of the principles of inheritance described by Gregor Mendel in the 1860s. In contrast to Mendel's notion that traits are independently assorted when passed from parent to child—for example that a cat's hair color and its tail length are inherited independent of each other—Bateson and Punnett showed that certain genes associated with physical traits can be inherited together, or genetically linked. In 1911, after observing that linked traits could on occasion be inherited separately, Thomas Hunt Morgan suggested that "crossovers" can occur between linked genes, where one of the linked genes physically crosses over to a different chromosome. Two decades Barbara McClintock and Harriet Creighton demonstrated that chromosomal crossover occurs during meiosis, the process of cell division by which sperm and egg cells are made.
Within the same year as McClintock's discovery, Curt Stern showed that crossing over—later called "recombination"—could occur in somatic cells like white blood cells and skin cells that divide through mitosis. In 1947, the microbiologist Joshua Lederberg showed that bacteria—which had been assumed to reproduce only asexually through binary fission—are capable of genetic recombination, more similar to sexual reproduction; this work established E. coli as a model organism in genetics, helped Lederberg win the 1958 Nobel Prize in Physiology or Medicine. Building on studies in fungi, in 1964 Robin Holliday proposed a model for recombination in meiosis which introduced key details of how the process can work, including the exchange of material between chromosomes through Holliday junctions. In 1983, Jack Szostak and colleagues presented a model now known as the DSBR pathway, which accounted for observations not explained by the Holliday model. During the next decade, experiments in Drosophila, budding yeast and mammalian cells led to the emergence of other models of homologous recombination, called SDSA pathways, which do not always rely on Holliday junctions.
Much of the work identifying proteins involved in the process and determining their mechanisms has been performed by a number of individuals including James Haber, Patrick Sung, Stephen Kowalczykowski, others. Homologous recombination is essential to cell division in eukaryotes like plants, animals and protists. In cells that divide through mitosis, homologous recombination repairs double-strand breaks in DNA caused by ionizing radiation or DNA-damaging chemicals. Left unrepaired, these double-strand breaks can cause large-scale rearrangement of chromosomes in somatic cells, which can in turn lead to cancer. In addition to repairing DNA, homologous recombination helps produce genetic diversity when cells divide in meiosis to become specialized gamete cells—sperm or egg cells in animals, pollen o
Eukaryotes are organisms whose cells have a nucleus enclosed within membranes, unlike prokaryotes, which have no membrane-bound organelles. Eukaryotes belong to Eukarya, their name comes from the Greek εὖ and κάρυον. Eukaryotic cells contain other membrane-bound organelles such as mitochondria and the Golgi apparatus, in addition, some cells of plants and algae contain chloroplasts. Unlike unicellular archaea and bacteria, eukaryotes may be multicellular and include organisms consisting of many cell types forming different kinds of tissue. Animals and plants are the most familiar eukaryotes. Eukaryotes can reproduce both asexually through mitosis and sexually through meiosis and gamete fusion. In mitosis, one cell divides to produce two genetically identical cells. In meiosis, DNA replication is followed by two rounds of cell division to produce four haploid daughter cells; these act as sex cells. Each gamete has just one set of chromosomes, each a unique mix of the corresponding pair of parental chromosomes resulting from genetic recombination during meiosis.
The domain Eukaryota appears to be monophyletic, makes up one of the domains of life in the three-domain system. The two other domains and Archaea, are prokaryotes and have none of the above features. Eukaryotes represent a tiny minority of all living things. However, due to their much larger size, their collective worldwide biomass is estimated to be about equal to that of prokaryotes. Eukaryotes evolved 1.6–2.1 billion years ago, during the Proterozoic eon. The concept of the eukaryote has been attributed to the French biologist Edouard Chatton; the terms prokaryote and eukaryote were more definitively reintroduced by the Canadian microbiologist Roger Stanier and the Dutch-American microbiologist C. B. van Niel in 1962. In his 1937 work Titres et Travaux Scientifiques, Chatton had proposed the two terms, calling the bacteria prokaryotes and organisms with nuclei in their cells eukaryotes; however he mentioned this in only one paragraph, the idea was ignored until Chatton's statement was rediscovered by Stanier and van Niel.
In 1905 and 1910, the Russian biologist Konstantin Mereschkowski argued that plastids were reduced cyanobacteria in a symbiosis with a non-photosynthetic host, itself formed by symbiosis between an amoeba-like host and a bacterium-like cell that formed the nucleus. Plants had thus inherited photosynthesis from cyanobacteria. In 1967, Lynn Margulis provided microbiological evidence for endosymbiosis as the origin of chloroplasts and mitochondria in eukaryotic cells in her paper, On the origin of mitosing cells. In the 1970s, Carl Woese explored microbial phylogenetics, studying variations in 16S ribosomal RNA; this helped to uncover the origin of the eukaryotes and the symbiogenesis of two important eukaryote organelles and chloroplasts. In 1977, Woese and George Fox introduced a "third form of life", which they called the Archaebacteria. In 1979, G. W. Gould and G. J. Dring suggested that the eukaryotic cell's nucleus came from the ability of Gram-positive bacteria to form endospores. In 1987 and papers, Thomas Cavalier-Smith proposed instead that the membranes of the nucleus and endoplasmic reticulum first formed by infolding a prokaryote's plasma membrane.
In the 1990s, several other biologists proposed endosymbiotic origins for the nucleus reviving Mereschkowski's theory. Eukaryotic cells are much larger than those of prokaryotes having a volume of around 10,000 times greater than the prokaryotic cell, they have a variety of internal membrane-bound structures, called organelles, a cytoskeleton composed of microtubules and intermediate filaments, which play an important role in defining the cell's organization and shape. Eukaryotic DNA is divided into several linear bundles called chromosomes, which are separated by a microtubular spindle during nuclear division. Eukaryote cells include a variety of membrane-bound structures, collectively referred to as the endomembrane system. Simple compartments, called vesicles and vacuoles, can form by budding off other membranes. Many cells ingest food and other materials through a process of endocytosis, where the outer membrane invaginates and pinches off to form a vesicle, it is probable that most other membrane-bound organelles are derived from such vesicles.
Alternatively some products produced by the cell can leave in a vesicle through exocytosis. The nucleus is surrounded with pores that allow material to move in and out. Various tube- and sheet-like extensions of the nuclear membrane form the endoplasmic reticulum, involved in protein transport and maturation, it includes the rough endoplasmic reticulum where ribosomes are attached to synthesize proteins, which enter the interior space or lumen. Subsequently, they enter vesicles, which bud off from the smooth endoplasmic reticulum. In most eukaryotes, these protein-carrying vesicles are released and further modified in stacks of flattened vesicles, the Golgi apparatus. Vesicles may be specialized for various purposes. For instance, lysosomes contain digestive enzymes that break down most biomolecules in the cytoplasm. Peroxisomes are used to break down peroxide, otherwise toxic. Many protozoans have contractile vacuoles, which collect and expel excess water, extrusomes, which expel material used to deflect predators or capture prey.
In higher plants, most of a cell's volume is taken up by a central vacuole, whi
A model organism is a non-human species, extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workings of other organisms. Model organisms are used to research human disease when human experimentation would be unfeasible or unethical; this strategy is made possible by the common descent of all living organisms, the conservation of metabolic and developmental pathways and genetic material over the course of evolution. Studying model organisms can be informative, but care must be taken when generalizing from one organism to another. In researching human disease, model organisms allow for better understanding the disease process without the added risk of harming an actual human; the species chosen will meet a determined taxonomic equivalency to humans, so as to react to disease or its treatment in a way that resembles human physiology as needed. Although biological activity in a model organism does not ensure an effect in humans, many drugs and cures for human diseases are developed in part with the guidance of animal models.
There are three main types of disease models: homologous and predictive. Homologous animals have the same causes and treatment options as would humans who have the same disease. Isomorphic animals share the same treatments. Predictive models are similar to a particular human disease in only a couple of aspects, but are useful in isolating and making predictions about mechanisms of a set of disease features; the use of animals in research dates back to ancient Greece, with Aristotle and Erasistratus among the first to perform experiments on living animals. Discoveries in the 18th and 19th centuries included Antoine Lavoisier's use of a guinea pig in a calorimeter to prove that respiration was a form of combustion, Louis Pasteur's demonstration of the germ theory of disease in the 1880s using anthrax in sheep. Research using animal models has been central to many of the achievements of modern medicine, it has contributed most of the basic knowledge in fields such as human physiology and biochemistry, has played significant roles in fields such as neuroscience and infectious disease.
For example, the results have included the near-eradication of polio and the development of organ transplantation, have benefited both humans and animals. From 1910 to 1927, Thomas Hunt Morgan's work with the fruit fly Drosophila melanogaster identified chromosomes as the vector of inheritance for genes. Drosophila became one of the first, for some time the most used, model organisms, Eric Kandel wrote that Morgan's discoveries "helped transform biology into an experimental science." D. melanogaster remains one of the most used eukaryotic model organisms. During the same time period, studies on mouse genetics in the laboratory of William Ernest Castle in collaboration with Abbie Lathrop led to generation of the DBA inbred mouse strain and the systematic generation of other inbred strains; the mouse has since been used extensively as a model organism and is associated with many important biological discoveries of the 20th and 21st centuries. In the late 19th century, Emil von Behring isolated the diphtheria toxin and demonstrated its effects in guinea pigs.
He went on to develop an antitoxin against diphtheria in animals and in humans, which resulted in the modern methods of immunization and ended diphtheria as a threatening disease. The diphtheria antitoxin is famously commemorated in the Iditarod race, modeled after the delivery of antitoxin in the 1925 serum run to Nome; the success of animal studies in producing the diphtheria antitoxin has been attributed as a cause for the decline of the early 20th-century opposition to animal research in the United States. Subsequent research in model organisms led to further medical advances, such as Frederick Banting's research in dogs, which determined that the isolates of pancreatic secretion could be used to treat dogs with diabetes; this led to the 1922 discovery of insulin and its use in treating diabetes, which had meant death. John Cade's research in guinea pigs discovered the anticonvulsant properties of lithium salts, which revolutionized the treatment of bipolar disorder, replacing the previous treatments of lobotomy or electroconvulsive therapy.
Modern general anaesthetics, such as halothane and related compounds, were developed through studies on model organisms, are necessary for modern, complex surgical operations. In the 1940s, Jonas Salk used rhesus monkey studies to isolate the most virulent forms of the polio virus, which led to his creation of a polio vaccine; the vaccine, made publicly available in 1955, reduced the incidence of polio 15-fold in the United States over the following five years. Albert Sabin improved the vaccine by passing the polio virus through animal hosts, including monkeys, it has been estimated that developing and producing the vaccines required the use of 100,000 rhesus monkeys, with 65 doses of vaccine produced from each monkey. Sabin wrote in 1992, "Without the use of animals and human beings, it would have been impossible to acquire the important knowledge needed to prevent much suffering and premature death not only among humans, but among animals."Other 20th-century medical advances and treatments that relied on research performed in animals include organ transplant techniques, the heart-lung machine and the whooping cough vaccine.
Treatments for animal diseases have been developed, including for rabies, anthrax