HeLa is an immortal cell line used in scientific research. It is the oldest and most used human cell line; the line was derived from cervical cancer cells taken on February 8, 1951 from Henrietta Lacks, a patient who died of cancer on October 4, 1951. The cell line was found to be remarkably durable and prolific which warrants its extensive use in scientific research; the cells from Lacks's cancerous cervical tumor were taken without her consent. Cell biologist George Otto Gey found that they could be kept alive, isolated one specific cell, multiplied it, developed a cell line. Cells cultured from other human cells would only survive for a few days. Scientists would spend more time trying to keep the cells alive than performing actual research on them. Cells from Lacks's tumor behaved differently; as was custom for Gey's lab assistant, she labeled the culture'HeLa', the first two letters of the patient's first and last name. These were the first human cells grown in a lab that were "immortal", meaning that they do not die after a set number of cell divisions.
These cells could be used for conducting a multitude of medical experiments—if the cells died, they could be discarded and the experiment attempted again on fresh cells from the culture. This represented an enormous boon to medical and biological research, as stocks of living cells were limited and took significant effort to culture; the stable growth of HeLa enabled a researcher at the University of Minnesota hospital to grow polio virus, enabling the development of a vaccine, by 1952, Jonas Salk developed a vaccine for polio using these cells. To test Salk's new vaccine, the cells were put into mass production in the first-ever cell production factory. In 1953, HeLa cells were the first human cells cloned and demand for the HeLa cells grew in the nascent biomedical industry. Since the cells' first mass replications, they have been used by scientists in various types of investigations including disease research, gene mapping, effects of toxic substances on organisms, radiation on humans. Additionally, HeLa cells have been used to test human sensitivity to tape, glue and many other products.
Scientists have grown an estimated 50 million metric tons of HeLa cells, there are 11,000 patents involving these cells. The HeLa cell lines are notorious for invading other cell cultures in laboratory settings; some have estimated that HeLa cells have contaminated 10–20% of all cell lines in use. The cells were propagated by George Otto Gey shortly before Lacks died of her cancer in 1951; this was the first human cell line to prove successful in vitro, a scientific achievement with profound future benefit to medical research. Gey donated these cells along with the tools and processes that his lab developed to any scientist requesting them for the benefit of science. Neither Lacks nor her family gave permission to harvest the cells but, at that time, permission was neither required nor customarily sought; the cells were commercialized, although never patented in their original form. There was no requirement at that time to inform patients or their relatives about such matters because discarded material or material obtained during surgery, diagnosis, or therapy was the property of the physician or the medical institution.
This issue and Lacks' situation were brought up in the Supreme Court of California case of Moore v. Regents of the University of California; the court ruled that a person's discarded tissue and cells are not his or her property and can be commercialized. At first, the HeLa cell line was said to be named after a "Helen Lane" or "Helen Larson.” Starting in the 1970s the Lacks family was contacted by researchers trying to find out why the HeLa cells had contaminated other cell lines in laboratories. These cells are treated as cancer cells, as they are descended from a biopsy taken from a visible lesion on the cervix as part of Lacks' diagnosis of cancer. HeLa cells, like other cell lines, are termed "immortal" in that they can divide an unlimited number of times in a laboratory cell culture plate as long as fundamental cell survival conditions are met. There are many strains of HeLa cells as they continue to mutate in cell cultures, but all HeLa cells are descended from the same tumor cells removed from Lacks.
The total number of HeLa cells that have been propagated in cell culture far exceeds the total number of cells that were in Henrietta Lacks' body. HeLa cells were used by Jonas Salk to test the first polio vaccine in the 1950s, they were observed to be infected by poliomyelitis, causing infected cells to die. This made HeLa cells desirable for polio vaccine testing since results could be obtained. A large volume of HeLa cells were needed for the testing of Salk's polio vaccine, prompting the National Foundation for Infantile Paralysis to find a facility capable of mass-producing HeLa cells. In the spring of 1953, a cell culture factory was established at Tuskegee University to supply Salk and other labs with HeLa cells. Less than a year Salk's vaccine was ready for human trials. HeLa cells were the first human cells to be cloned in 1953 by Theodore Puck and Philip I Marcus at the University of Colorado, Denver. Since that time, HeLa cells have "continually been used for research into cancer, AIDS, the effects of radiation and toxic substances, gene mapping, countless other scientific pursuits."
According to author Rebecca Skloot, by 2009, "more than 60,000 scientific articles had been published about research done on HeLa, that nu
In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may be considered ligands which display both agonistic and antagonistic effects—when both a full agonist and partial agonist are present, the partial agonist acts as a competitive antagonist, competing with the full agonist for receptor occupancy and producing a net decrease in the receptor activation observed with the full agonist alone. Clinically, partial agonists can be used to activate receptors to give a desired submaximal response when inadequate amounts of the endogenous ligand are present, or they can reduce the overstimulation of receptors when excess amounts of the endogenous ligand are present; some common drugs that have been classed as partial agonists at particular receptors include buspirone, buprenorphine and norclozapine. Examples of ligands activating peroxisome proliferator-activated receptor gamma as partial agonists are honokiol and falcarindiol.
Delta 9-tetrahydrocannabivarin is a partial agonist at CB2 receptors and this activity might be implicated in ∆9-THCV-mediated anti-inflammatory effects. Competitive antagonist Intrinsic sympathomimetic activity of beta blockers Inverse agonist Mixed agonist/antagonist
Simplified molecular-input line-entry system
The simplified molecular-input line-entry system is a specification in the form of a line notation for describing the structure of chemical species using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules; the original SMILES specification was initiated in the 1980s. It has since been extended. In 2007, an open standard called. Other linear notations include the Wiswesser line notation, ROSDAL, SYBYL Line Notation; the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. Acknowledged for their parts in the early development were "Gilman Veith and Rose Russo and Albert Leo and Corwin Hansch for supporting the work, Arthur Weininger and Jeremy Scofield for assistance in programming the system." The Environmental Protection Agency funded the initial project to develop SMILES. It has since been modified and extended by others, most notably by Daylight Chemical Information Systems.
In 2007, an open standard called "OpenSMILES" was developed by the Blue Obelisk open-source chemistry community. Other'linear' notations include the Wiswesser Line Notation, ROSDAL and SLN. In July 2006, the IUPAC introduced the InChI as a standard for formula representation. SMILES is considered to have the advantage of being more human-readable than InChI; the term SMILES refers to a line notation for encoding molecular structures and specific instances should be called SMILES strings. However, the term SMILES is commonly used to refer to both a single SMILES string and a number of SMILES strings; the terms "canonical" and "isomeric" can lead to some confusion when applied to SMILES. The terms are not mutually exclusive. A number of valid SMILES strings can be written for a molecule. For example, CCO, OCC and CC all specify the structure of ethanol. Algorithms have been developed to generate the same SMILES string for a given molecule; this SMILES is unique for each structure, although dependent on the canonicalization algorithm used to generate it, is termed the canonical SMILES.
These algorithms first convert the SMILES to an internal representation of the molecular structure. Various algorithms for generating canonical SMILES have been developed and include those by Daylight Chemical Information Systems, OpenEye Scientific Software, MEDIT, Chemical Computing Group, MolSoft LLC, the Chemistry Development Kit. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database; the original paper that described the CANGEN algorithm claimed to generate unique SMILES strings for graphs representing molecules, but the algorithm fails for a number of simple cases and cannot be considered a correct method for representing a graph canonically. There is no systematic comparison across commercial software to test if such flaws exist in those packages. SMILES notation allows the specification of configuration at tetrahedral centers, double bond geometry; these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES.
A notable feature of these rules is. The term isomeric SMILES is applied to SMILES in which isotopes are specified. In terms of a graph-based computational procedure, SMILES is a string obtained by printing the symbol nodes encountered in a depth-first tree traversal of a chemical graph; the chemical graph is first trimmed to remove hydrogen atoms and cycles are broken to turn it into a spanning tree. Where cycles have been broken, numeric suffix labels are included to indicate the connected nodes. Parentheses are used to indicate points of branching on the tree; the resultant SMILES form depends on the choices: of the bonds chosen to break cycles, of the starting atom used for the depth-first traversal, of the order in which branches are listed when encountered. Atoms are represented by the standard abbreviation of the chemical elements, in square brackets, such as for gold. Brackets may be omitted in the common case of atoms which: are in the "organic subset" of B, C, N, O, P, S, F, Cl, Br, or I, have no formal charge, have the number of hydrogens attached implied by the SMILES valence model, are the normal isotopes, are not chiral centers.
All other elements must be enclosed in brackets, have charges and hydrogens shown explicitly. For instance, the SMILES for water may be written as either O or. Hydrogen may be written as a separate atom; when brackets are used, the symbol H is added if the atom in brackets is bonded to one or more hydrogen, followed by the number of hydrogen atoms if greater than 1 by the sign + for a positive charge or by - for a negative charge. For example, for ammonium. If there is more than one charge, it is written as digit.
European Chemicals Agency
The European Chemicals Agency is an agency of the European Union which manages the technical and administrative aspects of the implementation of the European Union regulation called Registration, Evaluation and Restriction of Chemicals. ECHA is the driving force among regulatory authorities in implementing the EU's chemicals legislation. ECHA helps companies to comply with the legislation, advances the safe use of chemicals, provides information on chemicals and addresses chemicals of concern, it is located in Finland. The agency headed by Executive Director Bjorn Hansen, started working on 1 June 2007; the REACH Regulation requires companies to provide information on the hazards and safe use of chemical substances that they manufacture or import. Companies register this information with ECHA and it is freely available on their website. So far, thousands of the most hazardous and the most used substances have been registered; the information is technical but gives detail on the impact of each chemical on people and the environment.
This gives European consumers the right to ask retailers whether the goods they buy contain dangerous substances. The Classification and Packaging Regulation introduces a globally harmonised system for classifying and labelling chemicals into the EU; this worldwide system makes it easier for workers and consumers to know the effects of chemicals and how to use products safely because the labels on products are now the same throughout the world. Companies need to notify ECHA of the labelling of their chemicals. So far, ECHA has received over 5 million notifications for more than 100 000 substances; the information is available on their website. Consumers can check chemicals in the products. Biocidal products include, for example, insect disinfectants used in hospitals; the Biocidal Products Regulation ensures that there is enough information about these products so that consumers can use them safely. ECHA is responsible for implementing the regulation; the law on Prior Informed Consent sets guidelines for the import of hazardous chemicals.
Through this mechanism, countries due to receive hazardous chemicals are informed in advance and have the possibility of rejecting their import. Substances that may have serious effects on human health and the environment are identified as Substances of Very High Concern 1; these are substances which cause cancer, mutation or are toxic to reproduction as well as substances which persist in the body or the environment and do not break down. Other substances considered. Companies manufacturing or importing articles containing these substances in a concentration above 0,1% weight of the article, have legal obligations, they are required to inform users about the presence of the substance and therefore how to use it safely. Consumers have the right to ask the retailer whether these substances are present in the products they buy. Once a substance has been identified in the EU as being of high concern, it will be added to a list; this list is available on ECHA's website and shows consumers and industry which chemicals are identified as SVHCs.
Substances placed on the Candidate List can move to another list. This means that, after a given date, companies will not be allowed to place the substance on the market or to use it, unless they have been given prior authorisation to do so by ECHA. One of the main aims of this listing process is to phase out SVHCs where possible. In its 2018 substance evaluation progress report, ECHA said chemical companies failed to provide “important safety information” in nearly three quarters of cases checked that year. "The numbers show a similar picture to previous years" the report said. The agency noted that member states need to develop risk management measures to control unsafe commercial use of chemicals in 71% of the substances checked. Executive Director Bjorn Hansen called non-compliance with REACH a "worry". Industry group CEFIC acknowledged the problem; the European Environmental Bureau called for faster enforcement to minimise chemical exposure. European Chemicals Bureau Official website
Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development and reproduction of all known organisms and many viruses. DNA and ribonucleic acid are nucleic acids; the two DNA strands are known as polynucleotides as they are composed of simpler monomeric units called nucleotides. Each nucleotide is composed of one of four nitrogen-containing nucleobases, a sugar called deoxyribose, a phosphate group; the nucleotides are joined to one another in a chain by covalent bonds between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone. The nitrogenous bases of the two separate polynucleotide strands are bound together, according to base pairing rules, with hydrogen bonds to make double-stranded DNA; the complementary nitrogenous bases are divided into two groups and purines. In DNA, the pyrimidines are cytosine. Both strands of double-stranded DNA store the same biological information.
This information is replicated as and when the two strands separate. A large part of DNA is non-coding, meaning that these sections do not serve as patterns for protein sequences; the two strands of DNA are thus antiparallel. Attached to each sugar is one of four types of nucleobases, it is the sequence of these four nucleobases along the backbone. RNA strands are created using DNA strands as a template in a process called transcription. Under the genetic code, these RNA strands specify the sequence of amino acids within proteins in a process called translation. Within eukaryotic cells, DNA is organized into long structures called chromosomes. Before typical cell division, these chromosomes are duplicated in the process of DNA replication, providing a complete set of chromosomes for each daughter cell. Eukaryotic organisms store most of their DNA inside the cell nucleus as nuclear DNA, some in the mitochondria as mitochondrial DNA, or in chloroplasts as chloroplast DNA. In contrast, prokaryotes store their DNA only in circular chromosomes.
Within eukaryotic chromosomes, chromatin proteins, such as histones and organize DNA. These compacting structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed. DNA was first isolated by Friedrich Miescher in 1869, its molecular structure was first identified by Francis Crick and James Watson at the Cavendish Laboratory within the University of Cambridge in 1953, whose model-building efforts were guided by X-ray diffraction data acquired by Raymond Gosling, a post-graduate student of Rosalind Franklin. DNA is used by researchers as a molecular tool to explore physical laws and theories, such as the ergodic theorem and the theory of elasticity; the unique material properties of DNA have made it an attractive molecule for material scientists and engineers interested in micro- and nano-fabrication. Among notable advances in this field are DNA origami and DNA-based hybrid materials. DNA is a long polymer made from repeating units called nucleotides.
The structure of DNA is dynamic along its length, being capable of coiling into tight loops and other shapes. In all species it is composed of two helical chains, bound to each other by hydrogen bonds. Both chains are coiled around the same axis, have the same pitch of 34 angstroms; the pair of chains has a radius of 10 angstroms. According to another study, when measured in a different solution, the DNA chain measured 22 to 26 angstroms wide, one nucleotide unit measured 3.3 Å long. Although each individual nucleotide is small, a DNA polymer can be large and contain hundreds of millions, such as in chromosome 1. Chromosome 1 is the largest human chromosome with 220 million base pairs, would be 85 mm long if straightened. DNA does not exist as a single strand, but instead as a pair of strands that are held together; these two long strands coil in the shape of a double helix. The nucleotide contains both a segment of the backbone of a nucleobase. A nucleobase linked to a sugar is called a nucleoside, a base linked to a sugar and to one or more phosphate groups is called a nucleotide.
A biopolymer comprising multiple linked nucleotides is called a polynucleotide. The backbone of the DNA strand is made from alternating sugar residues; the sugar in DNA is 2-deoxyribose, a pentose sugar. The sugars are joined together by phosphate groups that form phosphodiester bonds between the third and fifth carbon atoms of adjacent sugar rings; these are known as the 3′-end, 5′-end carbons, the prime symbol being used to distinguish these carbon atoms from those of the base to which the deoxyribose forms a glycosidic bond. When imagining DNA, each phosphoryl is considered to "belong" to the nucleotide whose 5′ carbon forms a bond therewith. Any DNA strand therefore has one end at which there is a phosphoryl attached to the 5′ carbon of a ribose and another end a
Xenopus is a genus of aquatic frogs native to sub-Saharan Africa. Twenty species are described within it; the two best-known species of this genus are Xenopus laevis and Xenopus tropicalis, which are studied as model organisms for developmental biology, cell biology, toxicology and for modelling human disease and birth defects. The genus is known for its polyploidy, with some species having up to 12 sets of chromosomes. All species of Xenopus have flattened, somewhat egg-shaped and streamlined bodies, slippery skin; the frog's skin is smooth, but with a lateral line sensory organ. The frogs are all excellent swimmers and have powerful webbed toes, though the fingers lack webbing. Three of the toes on each foot have conspicuous black claws; the frog's eyes are on top of the head. The pupils are circular, they have tongues or eardrums. Unlike most amphibians, they have no haptoglobin in their blood. Xenopus species are aquatic, though they have been observed migrating on land to nearby bodies of water during times of drought or in heavy rain.
They are found in lakes, swamps, potholes in streams, man-made reservoirs. Adult frogs are both predators and scavengers, since their tongues are unusable, the frogs use their small fore limbs to aid in the feeding process. Since they lack vocal sacs, they make clicks underwater. Males establish a hierarchy of social dominance in which one male has the right to make the advertisement call; the females of many species produce a release call, Xenopus laevis females produce an additional call when sexually receptive and soon to lay eggs. The Xenopus species are active during the twilight hours. During breeding season, the males develop ridge-like nuptial pads on their fingers to aid in grasping the female; the frogs' mating embrace is inguinal. Like many other anurans, they are used in laboratory as research subjects. Xenopus embryos and eggs are a popular model system for a wide variety of biological studies; this animal is used because of its powerful combination of experimental tractability and close evolutionary relationship with humans, at least compared to many model organisms.
Xenopus has long been an important tool for in vivo studies in molecular and developmental biology of vertebrate animals. However, the wide breadth of Xenopus research stems from the additional fact that cell-free extracts made from Xenopus are a premier in vitro system for studies of fundamental aspects of cell and molecular biology. Thus, Xenopus is the only vertebrate model system that allows for high-throughput in vivo analyses of gene function and high-throughput biochemistry. Furthermore, Xenopus oocytes are a leading system for studies of ion transport and channel physiology. Xenopus is a unique system for analyses of genome evolution and whole genome duplication in vertebrates, as different Xenopus species form a ploidy series formed by interspecific hybridization. Xenbase is the Model Organism Database for both Xenopus Xenopus tropicalis. In 1931, Lancelot Hogben noted that Xenopus laevis females ovulated when injected with the urine of pregnant women; this led to a pregnancy test, refined by South African researchers Hillel Abbe Shapiro and Harry Zwarenstein.
A female Xenopus frog injected with a woman's urine was put in a jar with a little water. If eggs were in the water a day it meant the woman was pregnant. Four years after the first Xenopus test, Zwarenstein's colleague, Dr Louis Bosman, reported that the test was accurate in more than 99% of cases. From the 1930s to the 1950s, thousands of frogs were exported across the world for use in these pregnancy tests. All modes of Xenopus research are used in direct studies of human disease genes and to study the basic science underlying initiation and progression of cancer. Xenopus embryos for in vivo studies of human disease gene function: Xenopus embryos are large and manipulated, moreover, thousands of embryos can be obtained in a single day. Indeed, Xenopus was the first vertebrate animal for which methods were developed to allow rapid analysis of gene function using misexpression. Injection of mRNA in Xenopus that led to the cloning of interferon. Moreover, the use of morpholino-antisense oligonucleotides for gene knockdowns in vertebrate embryos, now used, was first developed by Janet Heasman using Xenopus.
In recent years, these approaches have played in important role in studies of human disease genes. The mechanism of action for several genes mutated in human cystic kidney disorders have been extensively studied in Xenopus embryos, shedding new light on the link between these disorders and Wnt signaling. Xenopus embryos have provided a rapid test bed for validating newly discovered disease genes. For example, studies in Xenopus confirmed and elucidated the role of PYCR1 in cutis laxa with progeroid features. Transgenic Xenopus for studying transcriptional regulation of human disease genes: Xenopus embryos develop so transgenesis in Xenopus is a rapid and effective method for analyzing genomic regulatory sequences. In a recent study, mutations in the SMAD7 locus were revealed to associate with human colorectal cancer; the mutations lay in
Transcription is the first step of gene expression, in which a particular segment of DNA is copied into RNA by the enzyme RNA polymerase. Both DNA and RNA are nucleic acids. During transcription, a DNA sequence is read by an RNA polymerase, which produces a complementary, antiparallel RNA strand called a primary transcript. Transcription proceeds in the following general steps: RNA polymerase, together with one or more general transcription factors, binds to promoter DNA. RNA polymerase creates a transcription bubble; this is done by breaking the hydrogen bonds between complementary DNA nucleotides. RNA polymerase adds RNA nucleotides. RNA sugar-phosphate backbone forms with assistance from RNA polymerase to form an RNA strand. Hydrogen bonds of the RNA–DNA helix break, freeing the newly synthesized RNA strand. If the cell has a nucleus, the RNA may be further processed; this may include polyadenylation and splicing. The RNA may exit to the cytoplasm through the nuclear pore complex; the stretch of DNA transcribed into an RNA molecule is called a transcription unit and encodes at least one gene.
If the gene encodes a protein, the transcription produces messenger RNA. Alternatively, the transcribed gene may encode for non-coding RNA such as microRNA, ribosomal RNA, transfer RNA, or enzymatic RNA molecules called ribozymes. Overall, RNA helps synthesize and process proteins. In virology, the term may be used when referring to mRNA synthesis from an RNA molecule. For instance, the genome of a negative-sense single-stranded RNA virus may be template for a positive-sense single-stranded RNA; this is because the positive-sense strand contains the information needed to translate the viral proteins for viral replication afterwards. This process is catalyzed by a viral RNA replicase. A DNA transcription unit encoding for a protein may contain both a coding sequence, which will be translated into the protein, regulatory sequences, which direct and regulate the synthesis of that protein; the regulatory sequence before the coding sequence is called the five prime untranslated region. As opposed to DNA replication, transcription results in an RNA complement that includes the nucleotide uracil in all instances where thymine would have occurred in a DNA complement.
Only one of the two DNA strands serve as a template for transcription. The antisense strand of DNA is read by RNA polymerase from the 3' end to the 5' end during transcription; the complementary RNA is created in the opposite direction, in the 5' → 3' direction, matching the sequence of the sense strand with the exception of switching uracil for thymine. This directionality is because RNA polymerase can only add nucleotides to the 3' end of the growing mRNA chain; this use of only the 3' → 5' DNA strand eliminates the need for the Okazaki fragments that are seen in DNA replication. This removes the need for an RNA primer to initiate RNA synthesis, as is the case in DNA replication; the non-template strand of DNA is called the coding strand, because its sequence is the same as the newly created RNA transcript. This is the strand, used by convention when presenting a DNA sequence. Transcription has some proofreading mechanisms, but they are fewer and less effective than the controls for copying DNA.
As a result, transcription has a lower copying fidelity than DNA replication. Transcription is divided into initiation, promoter escape and termination. Transcription begins with the binding of RNA polymerase, together with one or more general transcription factors, to a specific DNA sequence referred to as a "promoter" to form an RNA polymerase-promoter "closed complex". In the "closed complex" the promoter DNA is still double-stranded. RNA polymerase, assisted by one or more general transcription factors unwinds 14 base pairs of DNA to form an RNA polymerase-promoter "open complex". In the "open complex" the promoter DNA is unwound and single-stranded; the exposed, single-stranded DNA is referred to as the "transcription bubble."RNA polymerase, assisted by one or more general transcription factors selects a transcription start site in the transcription bubble, binds to an initiating NTP and an extending NTP complementary to the transcription start site sequence, catalyzes bond formation to yield an initial RNA product.
In bacteria, RNA polymerase holoenzyme consists of five subunits: 2 α subunits, 1 β subunit, 1 β' subunit, 1 ω subunit. In bacteria, there is one general RNA transcription factor: sigma. RNA polymerase core enzyme binds to the bacterial general transcription factor sigma to form RNA polymerase holoenzyme and binds to a promoter. In archaea and eukaryotes, RNA polymerase contains subunits homologous to each of the five RNA polymerase subunits in bacteria and contains additional subunits. In archaea and eukaryotes, the functions of the bacterial general transcription factor sigma are performed by multiple general transcription factors that work together. In archaea, there ar