1.
Ancient Greek
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Ancient Greek includes the forms of Greek used in ancient Greece and the ancient world from around the 9th century BC to the 6th century AD. It is often divided into the Archaic period, Classical period. It is antedated in the second millennium BC by Mycenaean Greek, the language of the Hellenistic phase is known as Koine. Koine is regarded as a historical stage of its own, although in its earliest form it closely resembled Attic Greek. Prior to the Koine period, Greek of the classic and earlier periods included several regional dialects, Ancient Greek was the language of Homer and of fifth-century Athenian historians, playwrights, and philosophers. It has contributed many words to English vocabulary and has been a subject of study in educational institutions of the Western world since the Renaissance. This article primarily contains information about the Epic and Classical phases of the language, Ancient Greek was a pluricentric language, divided into many dialects. The main dialect groups are Attic and Ionic, Aeolic, Arcadocypriot, some dialects are found in standardized literary forms used in literature, while others are attested only in inscriptions. There are also several historical forms, homeric Greek is a literary form of Archaic Greek used in the epic poems, the Iliad and Odyssey, and in later poems by other authors. Homeric Greek had significant differences in grammar and pronunciation from Classical Attic, the origins, early form and development of the Hellenic language family are not well understood because of a lack of contemporaneous evidence. Several theories exist about what Hellenic dialect groups may have existed between the divergence of early Greek-like speech from the common Proto-Indo-European language and the Classical period and they have the same general outline, but differ in some of the detail. The invasion would not be Dorian unless the invaders had some relationship to the historical Dorians. The invasion is known to have displaced population to the later Attic-Ionic regions, the Greeks of this period believed there were three major divisions of all Greek people—Dorians, Aeolians, and Ionians, each with their own defining and distinctive dialects. Often non-west is called East Greek, Arcadocypriot apparently descended more closely from the Mycenaean Greek of the Bronze Age. Boeotian had come under a strong Northwest Greek influence, and can in some respects be considered a transitional dialect, thessalian likewise had come under Northwest Greek influence, though to a lesser degree. Most of the dialect sub-groups listed above had further subdivisions, generally equivalent to a city-state and its surrounding territory, Doric notably had several intermediate divisions as well, into Island Doric, Southern Peloponnesus Doric, and Northern Peloponnesus Doric. The Lesbian dialect was Aeolic Greek and this dialect slowly replaced most of the older dialects, although Doric dialect has survived in the Tsakonian language, which is spoken in the region of modern Sparta. Doric has also passed down its aorist terminations into most verbs of Demotic Greek, by about the 6th century AD, the Koine had slowly metamorphosized into Medieval Greek
2.
Mitosis
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In cell biology, mitosis is a part of the cell cycle when replicated chromosomes are separated into two new nuclei. Mitosis and cytokinesis together define the phase of an animal cell cycle—the division of the mother cell into two daughter cells genetically identical to each other. The process of mitosis is divided into stages corresponding to the completion of one set of activities and these stages are prophase, prometaphase, metaphase, anaphase, and telophase. During mitosis, the chromosomes, which have already duplicated, condense, the result is two genetically identical daughter nuclei. The rest of the cell may then continue to divide by cytokinesis to produce two daughter cells, producing three or more daughter cells instead of normal two is a mitotic error called tripolar mitosis or multipolar mitosis. Other errors during mitosis can induce apoptosis or cause mutations, certain types of cancer can arise from such mutations. Mitosis occurs only in eukaryotic cells, prokaryotic cells, which lack a nucleus, divide by a different process called binary fission. Most animal cells undergo a change, known as mitotic cell rounding. Most human cells are produced by cell division. Important exceptions include the gametes – sperm and egg cells – which are produced by meiosis, german zoologist Otto Bütschli might have claimed the discovery of the process presently known as mitosis, a term coined by Walther Flemming in 1882. Mitosis was discovered in frog, rabbit, and cat cornea cells in 1873, the term is derived from the Greek word μίτος mitos warp thread. The primary result of mitosis and cytokinesis is the transfer of a parent cells genome into two daughter cells, the genome is composed of a number of chromosomes—complexes of tightly coiled DNA that contain genetic information vital for proper cell function. Because each resultant daughter cell should be identical to the parent cell. This occurs during the S phase of interphase, chromosome duplication results in two identical sister chromatids bound together by cohesin proteins at the centromere. When mitosis begins, the chromosomes condense and become visible, in some eukaryotes, for example animals, the nuclear envelope, which segregates the DNA from the cytoplasm, disintegrates into small vesicles. The nucleolus, which makes ribosomes in the cell, also disappears, microtubules project from opposite ends of the cell, attach to the centromeres, and align the chromosomes centrally within the cell. The microtubules then contract to pull the chromatids of each chromosome apart. Sister chromatids at this point are called daughter chromosomes, as the cell elongates, corresponding daughter chromosomes are pulled toward opposite ends of the cell and condense maximally in late anaphase
3.
Eukaryote
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A eukaryote is any organism whose cells contain a nucleus and other organelles enclosed within membranes. Eukaryotes belong to the taxon Eukarya or Eukaryota, the presence of a nucleus gives eukaryotes their name, which comes from the Greek εὖ and κάρυον. Eukaryotic cells also contain other membrane-bound organelles such as mitochondria and the Golgi apparatus, in addition, plants and algae contain chloroplasts. Eukaryotic organisms may be unicellular or multicellular, only eukaryotes form multicellular organisms consisting of many kinds of tissue made up of different cell types. Eukaryotes can reproduce asexually through mitosis and sexually through meiosis and gamete fusion. In mitosis, one cell divides to produce two identical cells. In meiosis, DNA replication is followed by two rounds of division to produce four daughter cells each with half the number of chromosomes as the original parent cell. These act as sex cells resulting from genetic recombination during meiosis, the domain Eukaryota appears to be monophyletic, and so makes up one of the three domains of life. The two other domains, Bacteria and Archaea, are prokaryotes and have none of the above features, eukaryotes represent a tiny minority of all living things. However, due to their larger size, eukaryotes collective worldwide biomass is estimated at about equal to that of prokaryotes. Eukaryotes first developed approximately 1. 6–2.1 billion years ago, in 1905 and 1910, the Russian biologist Konstantin Mereschkowsky argued three things about the origin of nucleated cells. Firstly, plastids were reduced cyanobacteria in a symbiosis with a non-photosynthetic host, secondly, the host had earlier in evolution formed by symbiosis between an amoeba-like host and a bacteria-like cell that formed the nucleus. Thirdly, plants inherited photosynthesis from cyanobacteria, the split between the prokaryotes and eukaryotes was introduced in the 1960s. 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 1938 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 one paragraph, and the idea was effectively ignored until Chattons statement was rediscovered by Stanier. In 1967, Lynn Margulis provided microbiological evidence for endosymbiosis as the origin of chloroplasts and mitochondria in cells in her paper. In the 1970s, Carl Woese explored microbial phylogenetics, studying variations in 16S ribosomal RNA and this helped to uncover the origin of the eukaryotes and the symbiogenesis of two important eukaryote organelles, mitochondria and chloroplasts
4.
Cell cycle
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The cell cycle or cell-division cycle is the series of events that take place in a cell leading to its division and duplication of its DNA to produce two daughter cells. In bacteria, which lack a nucleus, the cell cycle is divided into the B, C. The B period extends from the end of cell division to the beginning of DNA replication, DNA replication occurs during the C period. The D period refers to the stage between the end of DNA replication and the splitting of the cell into two daughter cells. In cells with a nucleus, as in eukaryotes, the cycle is also divided into three periods, interphase, the mitotic phase, and cytokinesis. During interphase, the cell grows, accumulating nutrients needed for mitosis, preparing it for cell division, during the mitotic phase, the chromosomes separate. During the final stage, cytokinesis, the chromosomes and cytoplasm separate into two new daughter cells, to ensure the proper division of the cell, there are control mechanisms known as cell cycle checkpoints. After cell division, each of the cells begin the interphase of a new cycle. The cell cycle consists of four phases, G1 phase, S phase, G2 phase. Activation of each phase is dependent on the progression and completion of the previous one. Cells that have temporarily or reversibly stopped dividing are said to have entered a state of quiescence called G0 phase, after cell division, each of the daughter cells begin the interphase of a new cycle. G0 is a phase where the cell has left the cycle and has stopped dividing. The cell cycle starts with this phase, the word post-mitotic is sometimes used to refer to both quiescent and senescent cells. Non proliferative cells in multicellular eukaryotes generally enter the quiescent G0 state from G1 and may remain quiescent for long periods of time and this is very common for cells that are fully differentiated. Cellular senescence occurs in response to DNA damage and external stress, some cells enter the G0 phase semi-permanently, and are considered post-mitotic e. g. some liver, kidney, stomach cells. Many cells do not enter G0 and continue to divide throughout an organisms life, before a cell can enter cell division, it needs to take in nutrients. All of the preparations are done during interphase, interphase is a series of changes that takes place in a newly formed cell and its nucleus, before it becomes capable of division again. It is also called preparatory phase or intermitosis, previously it was called resting stage because there is no apparent activity related to cell division. Typically interphase lasts for at least 90% of the total time required for the cell cycle
5.
Anaphase
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Anaphase, is the stage of mitosis after the metaphase when replicated chromosomes are split and the daughter chromatids are moved to opposite poles of the cell. Chromosomes also reach their overall maximum condensation in late anaphase, to chromosome segregation. Anaphase starts when the anaphase promoting complex marks an inhibitory chaperone called securin with ubiquitin for destruction, securin is a protein which inhibits a protease known as separase. The destruction of securin unleashes separase which then breaks down cohesin, the centromeres are split, and the new daughter chromosomes are pulled toward the poles. They take on a V-shape or Y-shape as they are pulled back, while the chromosomes are drawn to each side of the cell, the non-kinetochore spindle fibers push against each other, in a ratcheting action, that stretches the cell into an oval. Once anaphase is complete, the moves into telophase. Anaphase accounts for approximately 1% of the cell cycles duration and it begins with the regulated triggering of the metaphase-to-anaphase transition. Metaphase ends with the destruction of B cyclin, B cyclin is marked with ubiquitin which flags it for destruction by proteasomes, which is required for the function of metaphase cyclin-dependent kinases. Interphase Prophase Metaphase Telophase Anaphase I Anaphase II Cdc20 Media related to Anaphase at Wikimedia Commons
6.
Chromosome
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A chromosome is a DNA molecule with part or all of the genetic material of an organism. Prokaryotes usually have one single circular chromosome, whereas most eukaryotes are diploid, chromosomes in eukaryotes are composed of chromatin fiber. Chromatin fiber is made of nucleosomes, a nucleosome is a histone octamer with part of a longer DNA strand attached to and wrapped around it. Chromatin fiber, together with associated proteins is known as chromatin, chromatin is present in most cells, with a few exceptions, for example, red blood cells. Occurring only in the nucleus of cells, chromatin contains the vast majority of DNA, except for a small amount inherited maternally. Chromosomes are normally visible under a microscope only when the cell is undergoing the metaphase of cell division. Before this happens every chromosome is copied once, and the copy is joined to the original by a centromere resulting in an X-shaped structure, the original chromosome and the copy are now called sister chromatids. During metaphase, when a chromosome is in its most condensed state, in this highly condensed form chromosomes are easiest to distinguish and study. In prokaryotic cells, chromatin occurs free-floating in cytoplasm, as these cells lack organelles, the main information-carrying macromolecule is a single piece of coiled double-helix DNA, containing many genes, regulatory elements and other noncoding DNA. The DNA-bound macromolecules are proteins that serve to package the DNA, chromosomes vary widely between different organisms. Some species such as certain bacteria also contain plasmids or other extrachromosomal DNA and these are circular structures in the cytoplasm that contain cellular DNA and play a role in horizontal gene transfer. Chromosomal recombination during meiosis and subsequent sexual reproduction plays a significant role in genetic diversity. In prokaryotes and viruses, the DNA is often densely packed and organized, in the case of archaea, by homologs to eukaryotic histones, small circular genomes called plasmids are often found in bacteria and also in mitochondria and chloroplasts, reflecting their bacterial origins. Some use the term chromosome in a sense, to refer to the individualized portions of chromatin in cells. However, others use the concept in a sense, to refer to the individualized portions of chromatin during cell division. The word chromosome comes from the Greek χρῶμα and σῶμα, describing their strong staining by particular dyes, schleiden, Virchow and Bütschli were among the first scientists who recognized the structures now so familiar to everyone as chromosomes. The term was coined by von Waldeyer-Hartz, referring to the term chromatin, in a series of experiments beginning in the mid-1880s, Theodor Boveri gave the definitive demonstration that chromosomes are the vectors of heredity. His two principles were the continuity of chromosomes and the individuality of chromosomes and it is the second of these principles that was so original
7.
Nucleic acid sequence
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A nucleic acid sequence is a succession of letters that indicate the order of nucleotides within a DNA or RNA molecule. By convention, sequences are presented from the 5 end to the 3 end. For DNA, the strand is used. Because nucleic acids are linear polymers, specifying the sequence is equivalent to defining the covalent structure of the entire molecule. For this reason, the nucleic acid sequence is also termed the primary structure, the sequence has capacity to represent information. Biological deoxyribonucleic acid represents the information which directs the functions of a living thing, nucleic acids also have a secondary structure and tertiary structure. Primary structure is sometimes referred to as primary sequence. Conversely, there is no concept of secondary or tertiary sequence. Nucleic acids consist of a chain of linked units called nucleotides, each nucleotide consists of three subunits, a phosphate group and a sugar make up the backbone of the nucleic acid strand, and attached to the sugar is one of a set of nucleobases. The nucleobases are important in base pairing of strands to form secondary and tertiary structure such as the famed double helix. The possible letters are A, C, G, and T, in the typical case, the sequences are printed abutting one another without gaps, as in the sequence AAAGTCTGAC, read left to right in the 5 to 3 direction. With regards to transcription, a sequence is on the strand if it has the same order as the transcribed RNA. One sequence can be complementary to sequence, meaning that they have the base on each position in the complementary. For example, the sequence to TTAC is GTAA. If one strand of the double-stranded DNA is considered the sense strand, then the other strand, considered the antisense strand, will have the complementary sequence to the sense strand. Apart from adenine, cytosine, guanine, thymine and uracil, in DNA, the most common modified base is 5-methylcytidine. In RNA, there are many modified bases, including pseudouridine, dihydrouridine, inosine, ribothymidine and 7-methylguanosine, hypoxanthine and xanthine are two of the many bases created through mutagen presence, both of them through deamination. Hypoxanthine is produced from adenine, xanthine from guanine, similarly, deamination of cytosine results in uracil
8.
Cell (biology)
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The cell is the basic structural, functional, and biological unit of all known living organisms. A cell is the smallest unit of life that can replicate independently, the study of cells is called cell biology. Cells consist of cytoplasm enclosed within a membrane, which contains many such as proteins. Organisms can be classified as unicellular or multicellular, while the number of cells in plants and animals varies from species to species, humans contain more than 10 trillion cells. Most plant and animal cells are only under a microscope. The cell was discovered by Robert Hooke in 1665, who named the unit for its resemblance to cells inhabited by Christian monks in a monastery. Cells emerged on Earth at least 3.5 billion years ago, Cells are of two types, eukaryotic, which contain a nucleus, and prokaryotic, which do not. Prokaryotes are single-celled organisms, while eukaryotes can be either single-celled or multicellular, prokaryotic cells were the first form of life on Earth, characterised by having vital biological processes including cell signaling and being self-sustaining. They are simpler and smaller than eukaryotic cells, and lack membrane-bound organelles such as the nucleus, prokaryotes include two of the domains of life, bacteria and archaea. The DNA of a prokaryotic cell consists of a chromosome that is in direct contact with the cytoplasm. The nuclear region in the cytoplasm is called the nucleoid, most prokaryotes are the smallest of all organisms ranging from 0.5 to 2.0 µm in diameter. Though most prokaryotes have both a cell membrane and a wall, there are exceptions such as Mycoplasma and Thermoplasma which only possess the cell membrane layer. The envelope gives rigidity to the cell and separates the interior of the cell from its environment, the cell wall consists of peptidoglycan in bacteria, and acts as an additional barrier against exterior forces. It also prevents the cell from expanding and bursting from osmotic pressure due to a hypotonic environment, some eukaryotic cells also have a cell wall. Inside the cell is the region that contains the genome, ribosomes. The genetic material is found in the cytoplasm. Prokaryotes can carry extrachromosomal DNA elements called plasmids, which are usually circular, linear bacterial plasmids have been identified in several species of spirochete bacteria, including members of the genus Borrelia notably Borrelia burgdorferi, which causes Lyme disease. Though not forming a nucleus, the DNA is condensed in a nucleoid, plasmids encode additional genes, such as antibiotic resistance genes
9.
Prometaphase
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Prometaphase is the phase of mitosis following prophase and preceding metaphase, in eukaryotic somatic cells. Prometaphase is sometimes included as part of the end of prophase. In prometaphase, the nuclear membrane breaks apart into numerous membrane vesicles, kinetochore microtubules emerging from the centrosomes at the poles of the spindle reach the chromosomes and attach to the kinetochores, throwing the chromosomes into agitated motion. Other spindle microtubules make contact with microtubules coming from the opposite pole, forces exerted by protein motors associated with spindle microtubules move the chromosomes toward the center of the cell. The microtubules are composed of two types, kinetochore microtubules and non-kinetochore microtubules, kinetochore microtubules begin searching for kinetochores to attach to. A number of microtubules or polar microtubules find and interact with corresponding nonkinetochore microtubules from the opposite centrosome to form the mitotic spindle. The role of prometaphase is completed all of the kinetochore microtubules have attached to their kinetochores. An unattached kinetochore, and thus a non-aligned chromosome, even when most of the chromosomes have lined up. This prevents premature progression into anaphase by inhibiting the complex until all kinetochores are attached. Media related to Prometaphase at Wikimedia Commons
10.
Microtubule
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Microtubules are a component of the cytoskeleton, found throughout the cytoplasm. These tubular polymers of tubulin can grow as long as 50 micrometres and are highly dynamic, the outer diameter of a microtubule is about 24 nm while the inner diameter is about 12 nm. They are found in cells, as well as some bacteria. Microtubules are very important in a number of cellular processes and they are involved in maintaining the structure of the cell and, together with microfilaments and intermediate filaments, they form the cytoskeleton. They also make up the structure of cilia and flagella. They are also involved in chromosome separation, and are the constituents of mitotic spindles. There are many proteins bind to microtubules, including the motor proteins kinesin and dynein, severing proteins like katanin. Recently an actin-like protein has found in a gram-positive bacterium Bacillus thuringiensis. Tubulin and microtubule-mediated processes, like cell locomotion, were seen by early microscopists, in eukaryotes, microtubules are long, hollow cylinders made up of polymerised α- and β-tubulin dimers. The inner space of the hollow microtubule cylinders is referred to as the lumen, the α and β-tubulin subunits are approximately 50% identical at the amino acid level, and each have a molecular weight of approximately 50 kDa. These α/β-tubulin dimers polymerize end-to-end into linear protofilaments that associate laterally to form a single microtubule, typically, microtubules are formed by the parallel association of thirteen protofilaments, although microtubules composed of fewer or more protofilaments have been observed in vitro. Microtubules have a polarity that is critical for their biological function. Tubulin polymerizes end to end, with the β-subunits of one tubulin dimer contacting the α-subunits of the next dimer, therefore, in a protofilament, one end will have the α-subunits exposed while the other end will have the β-subunits exposed. These ends are designated the and ends, respectively, while microtubule elongation can occur at both the and ends, it is significantly more rapid at the end. The lateral association of the protofilaments generates a pseudo-helical structure, with one turn of the helix containing 13 tubulin dimers, each from a different protofilament. In the most common 13-3 architecture, the 13th tubulin dimer interacts with the tubulin dimer with a vertical offset of 3 tubulin monomers due to the helicity of the turn. There are other alternative architectures, such as 11-3, 12-3, 14-3, 15-4, or 16-4, Microtubules can also morph into other forms such as helical filaments, which are observed in protist organisms like foraminifera. There are two types of interactions that can occur between the subunits of lateral protofilaments within the microtubule called the A-type and B-type lattices
11.
Prophase
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Prophase, is a stage of Mitosis. This is when the chromatin condenses into two rod-shaped structures called chromosomes in which the chromatin becomes visible and this process, known as chromatin condensation, is involved with the condensin complex. Since the genetic material has been replicated in the interphase of the cell cycle. Those copies are called sister chromatids and they are attached to each other at a DNA element present on every chromosome called the centromere, also during prophase, giemsa staining can be applied to elicit G-banding in chromosomes. An important organelle in mitosis is the centrosome, the organizing center in metazoans. During prophase, the two centrosomes, which replicate independently of mitosis, have their microtubule-activity increased due to the recruitment of γ-tubulin, the centrosomes will be pushed apart to opposite ends of the cell nucleus by the action of molecular motors acting on the microtubules. At the end of prophase, the tiny nucleolus within the nucleus dissolves, the nucleolus starts moving towards the nuclear membrane at the beginning of prophase, and its disintegration occurs near the nuclear envelope. Its contents are dispersed in masses, basically, the chromatin in the nucleus coils into chromosomes. The centrosomes move to opposite poles of the cell, forming a bridge of spindle fibers, at the end of prophase, the nucleolus disperses. In prometaphase, the step of mitosis, the nuclear membrane breaks apart. Interphase Metaphase Anaphase Telophase Farhan Phase Media related to Prophase at Wikimedia Commons
12.
Kinetochore
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Kinetochore, protein structure found at the centromere of a chromatid to which microtubules attach to during cell division. The kinetochore is a structure on chromatids where the spindle fibers attach during cell division to pull sister chromatids apart. Their proteins help to hold the sister chromatids together and also play a role in chromosome editing, the kinetochore forms in eukaryotes, assembles on the centromere and links the chromosome to microtubule polymers from the mitotic spindle during mitosis and meiosis. Monocentric organisms, including vertebrates, fungi, and most plants, have a single region on each chromosome which assembles one kinetochore. Holocentric organisms, such as nematodes and some plants, assemble a kinetochore along the length of a chromosome. Kinetochores start, control, and supervise the movements of chromosomes during cell division. Thus, the kinetochore is essential for the segregation that is classically associated with mitosis and meiosis. Even the simplest kinetochores consist of more than 19 different proteins, many of these proteins are conserved between eukaryotic species, including a specialized histone H3 variant which helps the kinetochore associate with DNA. Other proteins in the kinetochore attach it to the microtubules of the mitotic spindle, there are also motor proteins, including both dynein and kinesin, which generate forces that move chromosomes during mitosis. On the other hand, MTs are metastable polymers made of α- and β-tubulin, MTs are highly dynamic structures, whose behavior is integrated with kinetochore function to control chromosome movement and segregation. The kinetochore is composed of layers, observed initially by conventional fixation and staining methods of electron microscopy. The deepest layer in the kinetochore is the plate, which is organized on a chromatin structure containing nucleosomes presenting a specialized histone, auxiliary proteins. DNA organization in the centromere is one of the least known aspects in vertebrate kinetochores, the inner plate appears like a discrete heterochromatin domain throughout the cell cycle. Outside the inner plate we find the outer plate, composed mostly by proteins and this structure is assembled in the surface of the chromosomes when the nuclear envelope breaks down. The outer plate in vertebrate kinetochores contains about 20 anchoring sites for MTs ends, the outermost domain in the kinetochore forms a fibrous corona, which can be visualized by conventional microscopy, yet only in absence of MTs. This corona is formed by a network of resident and temporary proteins implicated in the spindle checkpoint, in MTs anchoring. During mitosis, each sister chromatid forming the complete chromosome has its own kinetochore, distinct sister kinetochores can be observed at first at the end of G2 phase in cultured mammalian cells. These early kinetochores show a mature laminar structure before the nuclear envelope breaks down, yet no simple linear route can describe the data obtained so far
13.
Centromere
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The centromere is the part of a chromosome that links sister chromatids or a dyad. During mitosis, spindle fibers attach to the centromere via the kinetochore, centromeres were first thought to be genetic loci that direct the behavior of chromosomes. e. There are, broadly speaking, two types of centromeres, point centromeres bind to specific proteins that recognise particular DNA sequences with high efficiency. Any piece of DNA with the point centromere DNA sequence on it will form a centromere if present in the appropriate species. The best characterised point centromeres are those of the budding yeast, regional centromeres is the term coined to describe most centromeres, which typically form on regions of preferred DNA sequence, but which can form on other DNA sequences as well. The signal for formation of a regional centromere appears to be epigenetic, most organisms, ranging from the fission yeast Schizosaccharomyces pombe to humans, have regional centromeres. Regarding mitotic chromosome structure, centromeres represent a region of the chromosome where two identical sister chromatids are most closely in contact. When cells enter mitosis, the chromatids are linked along their length by the action of the cohesin complex. Each chromosome has two arms, labeled p and q, many remember that the short arm p is named for the French word petit meaning small, although this explanation was shown to be apocryphal. They can be connected in either metacentric, submetacentric, acrocentric or telocentric manner and these are X-shaped chromosomes, with the centromere in the middle so that the two arms of the chromosomes are almost equal. A chromosome is metacentric if its two arms are equal in length. In a normal karyotype, five chromosomes are considered metacentric, chromosomes 1,3,16,19. In some cases, a chromosome is formed by balanced translocation. If arms lengths are unequal, the chromosome is said to be submetacentric, if the p arm is so short that it is hard to observe, but still present, then the chromosome is acrocentric. The human genome includes six acrocentric chromosomes,13,14,15,21,22, the domestic horse genome includes one metacentric chromosome that is homologous to two acrocentric chromosomes in the conspecific but undomesticated Przewalskis horse. A telocentric chromosomes centromere is located at the end of the chromosome. Telomeres may extend from both ends of the chromosome, for example, the standard house mouse karyotype has only telocentric chromosomes. Humans do not possess telocentric chromosomes, if the chromosomes centromere is located closer to its end than to its center, it may be described as subtelocentric
14.
Centrosome
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In cell biology, the centrosome is an organelle that serves as the main microtubule organizing center of the animal cell as well as a regulator of cell-cycle progression. The centrosome is thought to have evolved only in the lineage of eukaryotic cells. Fungi and plants lack centrosomes and therefore use other MTOC structures to organize their microtubules, although the centrosome has a key role in efficient mitosis in animal cells, it is not essential in certain fly and flatworm species. Centrosomes are composed of two orthogonally arranged centrioles surrounded by a mass of protein termed the pericentriolar material. The PCM contains proteins responsible for microtubule nucleation and anchoring including γ-tubulin, pericentrin and ninein, in general, each centriole of the centrosome is based on a nine triplet microtubule assembled in a cartwheel structure, and contains centrin, cenexin and tektin. In many cell type the Centrosome is replaced by a Cilium during cellular difrentiation, however, once the cell start to divide, the cilium is replaced back by the Centrosome. It was discovered by Edouard Van Beneden in 1883, and later described and named in 1888 by Theodor Boveri, centrosomes are associated with the nuclear membrane during prophase of the cell cycle. In mitosis the nuclear membrane breaks down and the centrosome nucleated microtubules can interact with the chromosomes to build the mitotic spindle, the mother centriole, the older of the two in the centriole pair, also has a central role in making cilia and flagella. The centrosome is copied once per cell cycle so that each daughter cell inherits one centrosome. The centrosome replicates during the S phase of the cell cycle, during the prophase in the process of cell division called mitosis, the centrosomes migrate to opposite poles of the cell. The mitotic spindle forms between the two centrosomes. Upon division, each daughter cell receives one centrosome, aberrant numbers of centrosomes in a cell have been associated with cancer. Doubling of a centrosome is similar to DNA replication in two respects, the nature of the process and the action of cdk2 as a regulator of the process. But the processes are different in that centrosome doubling does not occur by template reading. The mother centriole just aids in the accumulation of materials required for the assembly of the daughter centriole, interestingly, centrioles are not required for the progression of mitosis. When the centrioles are irradiated by a laser, mitosis proceeds normally with a morphologically normal spindle, moreover, development of the fruit fly Drosophila is largely normal when centrioles are absent due to a mutation in a gene required for their duplication. In the absence of the centrioles the microtubules of the spindle are focused by motors allowing the formation of a bipolar spindle, many cells can completely undergo interphase without centrioles. Unlike centrioles, centrosomes are required for survival of the organism, acentrosomal cells lack radial arrays of astral microtubules
15.
Cyclin
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Cyclins are a family of proteins that control the progression of cells through the cell cycle by activating cyclin-dependent kinase enzymes. Cyclins were originally discovered by R. Timothy Hunt in 1982 while studying the cell cycle of sea urchins, in an interview for The Life Scientific hosted by Jim Al-Khalili, R. Timothy Hunt explained that the name cyclin was originally named after his hobby cycling. It was only after the naming did its importance in the cell cycle become apparent, as it was appropriate the name stuck. R. Timothy Hunt, By the way, the cyclin, which I coined, was really a joke, its because I liked cycling so much at the time. Cyclins were originally named because their concentration varies in a fashion during the cell cycle. A cyclin forms a complex with Cdk, which begins to activate the Cdk, complex formation results in activation of the Cdk active site. Cyclins themselves have no enzymatic activity but have binding sites for some substrates, Cyclins, when bound with the dependent kinases, such as the p34/cdc2/cdk1 protein, form the maturation-promoting factor. MPFs activate other proteins through phosphorylation and these phosphorylated proteins, in turn, are responsible for specific events during cycle division such as microtubule formation and chromatin remodeling. Cyclins can be divided into four classes based on their behavior in the cycle of vertebrate somatic cells and yeast cells, G1 cyclins, G1/S cyclins, S cyclins. This division is useful when talking about most cell cycles, G1/S Cyclins rise in late G1 and fall in early S phase. The Cdk- G1/S cyclin complex begins to induce the initial processes of DNA replication, the cyclins also promote other activities to progress the cell cycle, such as centrosome duplication in vertebrates or spindle pole body in yeast. The rise in presence of G1/S cyclins is paralleled by a rise in S cyclins, G1 cyclins do not behave like the other cyclins, in that the concentrations increase gradually, throughout the cell cycle based on cell growth and the external growth-regulatory signals. The presence of G cyclins coordinate cell growth with the entry to a new cell cycle, S cyclins bind to Cdk and the complex directly induces DNA replication. The levels of S cyclins remain high, not only throughout S phase, M cyclin concentrations rise as the cell begins to enter mitosis and the concentrations peak at metaphase. Cell changes in the cell cycle like the assembly of mitotic spindles, the destruction of M cyclins during metaphase and anaphase, after the Spindle Assembly Checkpoint is satisfied, causes the exit of mitosis and cytokinesis. Cyclins are generally different from each other in primary structure. However, all members of the family are similar in 100 amino acids that make up the cyclin box. Cyclins contain two domains of a similar fold, the first located at the N-terminus and the second at the C-terminus
16.
Spindle checkpoint
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During the process of cell division, the spindle checkpoint prevents separation of the duplicated chromosomes until each chromosome is properly attached to the spindle apparatus. In order to preserve the identity and proper function, it is necessary to maintain the appropriate number of chromosomes after each cell division. An error in generating daughter cells with fewer or greater number of chromosomes than expected, may lead in best case to cell death, or alternatively it may generate catastrophic phenotypic results. In humans, Down syndrome appears in children carrying in their cells one extra copy of chromosome 21 and this defect will generate a gamete with an extra chromosome 21. After fertilisation, this gamete will generate an embryo with three copies of chromosome 21, the mechanisms verifying that all the requirements to pass to the next phase in the cell cycle have been fulfilled are called checkpoints. All along the cycle, there are different checkpoints. The checkpoint ensuring that chromosome segregation is correct is termed spindle assembly checkpoint, during mitosis or meiosis, the spindle checkpoint prevents anaphase onset until all chromosomes are properly attached to the spindle. To achieve proper segregation, the two kinetochores on the sister chromatids must be attached to spindle poles. Only this pattern of attachment will ensure that daughter cell receives one copy of the chromosome. Therefore, when the division process will end, each daughter cell will receive a complete set of organelles. At the same time, during S phase all cells must duplicate their DNA very precisely, the structure formed by the centrosomes and the microtubules is named mitotic spindle, due to its characteristic shape, holding the chromosomes between the two centrosomes. Both sister chromatids stay together until anaphase, at this moment they separate from each other, in this way, when the two daughter cells separate at the end of the division process, each one will receive a complete set of chromatids. The mechanism responsible for the distribution of sister chromatids during cell division is named chromosome segregation. To ensure that chromosome segregation takes place correctly, cells have developed a precise, during S phase, the centrosome starts to duplicate. Just at the beginning of mitosis, both centrioles achieve their maximal length, recruit additional material and their capacity to nucleate microtubules increases, as mitosis progresses, both centrosomes separate to generate the mitotic spindle. In this way, the spindle has two poles emanating microtubules. Each chromatid has a region, named the centromere, on top of which is assembled a proteic structure termed kinetochore. The chromosome plays an role in the attachment of kinetochores to the spindle
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Securin
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Securin is a protein involved in control of the metaphase-anaphase transition and anaphase onset. Securin is initially present in the cytoplasm and binds to separase, separase is vital for onset of anaphase. This securin-separase complex is maintained when securin is phosphorylated by Cdk1, when bound to securin, separase is not functional. In addition, both securin and separase are well-conserved proteins, note that separase cannot function without initially forming the securin-separase complex. This is because securin helps properly fold separase into the functional conformation, however, yeast does not appear to require securin to form functional separase as anaphase occurs in yeast with a securin deletion mutation. Securin has 5 known phosphorylation sites that are targets of Cdk1,2 sites at the N-terminal in the Ken-Box and D-box region are known to affect APC recognition and ubiquitination, to initiate the onset of anaphase, securin is dephosphorylated by Cdc14 and other phosphatases. Dephosphorylated securin is recognized by the Anaphase-Promoting Complex bound primarily to Cdc20, the APCCdc20 complex ubiquitinates securin and targets it for degradation. This results in free separase that is able to destroy cohesin and it is thought that securin integrates multiple regulatory inputs to make separase activation switch-like, resulting in sudden, coordinated anaphase. This likely involves a network with several loops, including positive feedback which leads to switch-like behavior. One proposed signaling pathway generating switch-like behavior contains a positive feedback loop for activation of Cdc14 by separase, in addition, these mutant strains exhibited very high rates of mis-segregation compared to normal behavior. Switch-like characteristics are necessary to trigger quick, coordinated chromosomal segregation in anaphase and this means that strong inactivation of separase by securin followed by sudden, rapid destruction of securin and activation of separase is vital for proper anaphase. Overall, securin and separase act in an anaphase-regulating network, figure 4 depicts a potential network diagram
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Separase
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In humans, separin is encoded by the ESPL1 gene. In S. cerevisiae, separase is encoded by the esp1 gene, Esp1 was discovered by Kim Nasmyth and coworkers in 1998. Stable cohesion between sister chromatids before anaphase and their separation during anaphase are critical for cell division. In vertebrates, sister chromatid cohesion is released in 2 steps via distinct mechanisms, the first step involves phosphorylation of STAG1 or STAG2 in the cohesin complex. The second step involves cleavage of the cohesin subunit SCC1 by separase, in S. cerevisiae, Esp1 is coded by ESP1 and is regulated by the securin Pds1. The proteins that bind the two chromatids, disallowing any premature sister chromatid separation, are a part of the cohesin protein family. One of these cohesin proteins crucial for sister chromatid cohesion is Scc1, Esp1 is a separase protein that cleaves the cohesin subunit Scc1, allowing sister chromatids to separate at the onset of anaphase during mitosis. When the cell is not dividing, separase is prevented from cleaving cohesin through its association with another protein, securin and this provides two layers of negative regulation to prevent inappropriate cohesin cleavage. Note that separase cannot function without initially forming the complex in most organisms. This is because securin helps properly fold separase into the functional conformation, however, yeast does not appear to require securin to form functional separase because anaphase occurs in yeast even with a securin deletion. On the signal for anaphase, securin is ubiquitinated and hydrolysed, active separase can then cleave Scc1 for release of the sister chromatids. Separase initiates the activation of Cdc14 in early anaphase and Cdc14 has been found to dephosphorylate securin, the presence of this positive feedback loop offers a potential mechanism for giving anaphase a more switch-like behavior
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Karyotype
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A karyotype is the number and appearance of chromosomes in the nucleus of a eukaryotic cell. The term is used for the complete set of chromosomes in a species or in an individual organism. Karyotypes describe the chromosome count of an organism and what these chromosomes look like under a light microscope, attention is paid to their length, the position of the centromeres, banding pattern, any differences between the sex chromosomes, and any other physical characteristics. The preparation and study of karyotypes is part of cytogenetics, the study of whole sets of chromosomes is sometimes known as karyology. The chromosomes are depicted in a format known as a karyogram or idiogram, in pairs, ordered by size. The basic number of chromosomes in the cells of an individual or a species is called the somatic number and is designated 2n. In the germ-line the chromosome number is n. p28 Thus, so, in normal diploid organisms, autosomal chromosomes are present in two copies. There may, or may not, be sex chromosomes, polyploid cells have multiple copies of chromosomes and haploid cells have single copies. The study of karyotypes is important for cell biology and genetics, Karyotypes can be used for many purposes, such as to study chromosomal aberrations, cellular function, taxonomic relationships, and to gather information about past evolutionary events. Chromosomes were first observed in plant cells by Carl Wilhelm von Nägeli in 1842 and their behavior in animal cells was described by Walther Flemming, the discoverer of mitosis, in 1882. The name was coined by another German anatomist, Heinrich von Waldeyer in 1888 and it is New Latin from Ancient Greek κάρυον karyon, kernel, seed, or nucleus, and τύπος typos, general form). The next stage took place after the development of genetics in the early 20th century, lev Delaunay seems to have been the first person to define the karyotype as the phenotypic appearance of the somatic chromosomes, in contrast to their genic contents. The subsequent history of the concept can be followed in the works of C. D. Darlington, investigation into the human karyotype took many years to settle the most basic question, how many chromosomes does a normal diploid human cell contain. In 1912, Hans von Winiwarter reported 47 chromosomes in spermatogonia and 48 in oogonia, concluding an XX/XO sex determination mechanism. Painter in 1922 was not certain whether the diploid of humans was 46 or 48, at first favouring 46, but revised his opinion from 46 to 48, considering the techniques of the time, these results were remarkable. In textbooks, the number of human chromosomes remained at 48 for over thirty years, New techniques were needed to correct this error. The work took place in 1955, and was published in 1956, the karyotype of humans includes only 46 chromosomes. Rather interestingly, the apes have 48 chromosomes
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Cytogenetics
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Cytogenetics is a branch of genetics that is concerned with how the chromosomes relate to cell behaviour, particularly to their behaviour during mitosis and meiosis. Chromosomes were first observed in plant cells by Karl Wilhelm von Nägeli in 1842 and their behavior in animal cells was described by Walther Flemming, the discoverer of mitosis, in 1882. The name was coined by another German anatomist, von Waldeyer in 1888, the next stage took place after the development of genetics in the early 20th century, when it was appreciated that the set of chromosomes was the carrier of the genes. Levitsky seems to have been the first to define the karyotype as the appearance of the somatic chromosomes. Investigation into the human karyotype took many years to settle the most basic question, in 1912, Hans von Winiwarter reported 47 chromosomes in spermatogonia and 48 in oogonia, concluding an XX/XO sex determination mechanism. Painter in 1922 was not certain whether the number of man was 46 or 48. He revised his opinion later from 46 to 48, and he insisted on man having an XX/XY system. Considering their techniques, these results were quite remarkable, in science books, the number of human chromosomes remained at 48 for over thirty years. New techniques were needed to correct this error and it took until 1956 until it became generally accepted that the karyotype of man included only 46 chromosomes. The great apes have 48 chromosomes, Human chromosome 2 was formed by a merger of ancestral chromosomes, reducing the number. Barbara McClintock began her career as a maize cytogeneticist, in 1931, McClintock and Harriet Creighton demonstrated that cytological recombination of marked chromosomes correlated with recombination of genetic traits. McClintock, while at the Carnegie Institution, continued studies on the mechanisms of chromosome breakage. She identified a particular chromosome breakage event that occurred at the same locus on maize chromosome 9. McClintock continued her career in studying the mechanics and inheritance of broken. During her cytogenetic work, McClintock discovered transposons, a find which led to her Nobel Prize in 1983. In the 1930s, Dobzhansky and his coworkers collected Drosophila pseudoobscura and D. persimilis from wild populations in California, using Painters technique they studied the polytene chromosomes and discovered that the wild populations were polymorphic for chromosomal inversions. All the flies look alike whatever inversions they carry, this is an example of a cryptic polymorphism, evidence rapidly accumulated to show that natural selection was responsible. Using a method invented by LHeretier and Teissier, Dobzhansky bred populations in population cages and this had the benefit of eliminating migration as a possible explanation of the results
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Mitotic inhibitor
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A mitotic inhibitor is a drug that inhibits mitosis, or cell division. These drugs disrupt microtubules, which are structures that pull the cell apart when it divides, mitotic inhibitors are used in cancer treatment, because cancer cells are able to grow and eventually spread through the body through continuous mitotic division. Thus, cancer cells are sensitive to inhibition of mitosis than normal cells. Mitotic inhibitors are used in cytogenetics, where they stop cell division at a stage where chromosomes can be easily examined. Mitotic inhibitors are derived from substances such as plant alkaloids. Microtubules are long, ropelike proteins that extend through the cell, microtubules are long polymers made of smaller units of the protein tubulin. Microtubules are created during normal cell functions by assembling tubulin components, one of the important functions of microtubules is to move and separate chromosomes and other components of the cell for cell division. Mitotic inhibitors interfere with the assembly and disassembly of tubulin into microtubule polymers and this interrupts cell division, usually during the mitosis phase of the cell cycle when two sets of fully formed chromosomes are supposed to separate into daughter cells. Examples of mitotic inhibitors used in the treatment of cancer include paclitaxel, docetaxel, vinblastine, vincristine. Colchicine and griseofulvin are mitotic inhibitors used in the treatment of gout and toenail fungus, cytogenetics, the study of chromosomal material by analysis of G-Banded chromosomes, uses mitotic inhibitors extensively. In order to prepare a slide for cytogenetic study, an inhibitor is added to the cells being studied. This stops the cells during mitosis, while the chromosomes are still visible, once the cells are centrifuged and placed in a hypotonic solution, they swell, spreading the chromosomes. After preparation, the chromosomes of the cells can be viewed under a microscope to have the banding patterns of the chromosomes examined and this experiment is crucial to many forms of cancer research. Taxanes are complex terpenes produced by the plants of the genus Taxus, originally derived from the Pacific yew tree, they are now synthesized artificially. Their principal mechanism is the disruption of the microtubule function by stabilizing microtubule formation. Microtubules are essential to mitotic reproduction, so through the inactivation of the function of a cell. Paclitaxel—used to treat cancer, ovarian cancer, breast cancer. Docetaxel—used to treat breast, ovarian, and non-small cell lung cancer, vinca alkaloids are amines produced by the hallucinogenic plant Catharanthus roseus
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Staining
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Staining is an auxiliary technique used in microscopy to enhance contrast in the microscopic image. Stains and dyes are used in biology and medicine to highlight structures in biological tissues for viewing. Stains may be used to define and examine bulk tissues, cell populations, in biochemistry it involves adding a class-specific dye to a substrate to qualify or quantify the presence of a specific compound. Staining and fluorescent tagging can serve similar purposes, biological staining is also used to mark cells in flow cytometry, and to flag proteins or nucleic acids in gel electrophoresis. Simple staining is staining with only one stain/dye, there are various kinds of multiple staining, many of which are examples of counterstaining, differential staining, or both, including double staining and triple staining. In vivo staining is the process of dyeing living tissues—in vivo means in life, by causing certain cells or structures to take on contrasting colour, their form or position within a cell or tissue can be readily seen and studied. In vitro staining involves colouring cells or structures that have removed from their biological context. Certain stains are often combined to reveal more details and features than a single stain alone, combined with specific protocols for fixation and sample preparation, scientists and physicians can use these standard techniques as consistent, repeatable diagnostic tools. A counterstain is stain that makes cells or structures more visible, for example, crystal violet stains only Gram-positive bacteria in Gram staining. A safranin counterstain is applied that stains all cells, allowing identification of Gram-negative bacteria, while ex vivo, many cells continue to live and metabolize until they are fixed. Some staining methods are based on this property and those stains excluded by the living cells but taken up by the already dead cells are called vital stains. Those that enter and stain living cells are called supravital stains, however, these stains are eventually toxic to the organism, some more so than others. To achieve desired effects, the stains are used in very dilute solutions ranging from 1,5000 to 1,500000, note that many stains may be used in both living and fixed cells. The preparatory steps involved depend on the type of analysis planned, fixation–which may itself consist of several steps–aims to preserve the shape of the cells or tissue involved as much as possible. Sometimes heat fixation is used to kill, adhere, and alter the specimen so it accepts stains, most chemical fixatives generate chemical bonds between proteins and other substances within the sample, increasing their rigidity. Common fixatives include formaldehyde, ethanol, methanol, and/or picric acid, pieces of tissue may be embedded in paraffin wax to increase their mechanical strength and stability and to make them easier to cut into thin slices. Permeabilization involves treatment of cells with a mild surfactant and this treatment dissolves cell membranes, and allows larger dye molecules into the cells interior. Mounting usually involves attaching the samples to a microscope slide for observation
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