Cytochromes P450 are proteins of the superfamily containing heme as a cofactor and, are hemeproteins. CYPs use a variety of large molecules as substrates in enzymatic reactions, they are, in general, the terminal oxidase enzymes in electron transfer chains, broadly categorized as P450-containing systems. The term "P450" is derived from the spectrophotometric peak at the wavelength of the absorption maximum of the enzyme when it is in the reduced state and complexed with carbon monoxide. CYP enzymes have been identified in all kingdoms of life: animals, fungi, bacteria, in viruses. However, they are not omnipresent. More than 50,000 distinct CYP proteins are known. Most CYPs require a protein partner to deliver one or more electrons to reduce the iron. Based on the nature of the electron transfer proteins, CYPs can be classified into several groups: Microsomal P450 systems, in which electrons are transferred from NADPH via cytochrome P450 reductase. Cytochrome b5 can contribute reducing power to this system after being reduced by cytochrome b5 reductase.
Mitochondrial P450 systems, which employ adrenodoxin reductase and adrenodoxin to transfer electrons from NADPH to P450. Bacterial P450 systems, which employ a ferredoxin reductase and a ferredoxin to transfer electrons to P450. CYB5R/cyb5/P450 systems, in which both electrons required by the CYP come from cytochrome b5. FMN/Fd/P450 systems found in Rhodococcus species, in which a FMN-domain-containing reductase is fused to the CYP. P450 only systems, which do not require external reducing power. Notable ones include thromboxane synthase, prostacyclin synthase, CYP74A; the most common reaction catalyzed by cytochromes P450 is a monooxygenase reaction, e.g. insertion of one atom of oxygen into the aliphatic position of an organic substrate while the other oxygen atom is reduced to water: RH + O2 + NADPH + H+ → ROH + H2O + NADP+ Many hydroxylation reactions use CYP enzymes. Genes encoding CYP enzymes, the enzymes themselves, are designated with the root symbol CYP for the superfamily, followed by a number indicating the gene family, a capital letter indicating the subfamily, another numeral for the individual gene.
The convention is to italicise the name. For example, CYP2E1 is the gene that encodes the enzyme CYP2E1—one of the enzymes involved in paracetamol metabolism; the CYP nomenclature is the official naming convention, although CYP450 or CYP450 is used synonymously. However, some gene or enzyme names for CYPs may differ from this nomenclature, denoting the catalytic activity and the name of the compound used as substrate. Examples include CYP5A1, thromboxane A2 synthase, abbreviated to TBXAS1, CYP51A1, lanosterol 14-α-demethylase, sometimes unofficially abbreviated to LDM according to its substrate and activity; the current nomenclature guidelines suggest that members of new CYP families share at least 40% amino acid identity, while members of subfamilies must share at least 55% amino acid identity. There are nomenclature committees that track both base gene names and allele names; the active site of cytochrome P450 contains a heme-iron center. The iron is tethered to the protein via a cysteine thiolate ligand.
This cysteine and several flanking residues are conserved in known CYPs and have the formal PROSITE signature consensus pattern - - x - - - - - C - -. Because of the vast variety of reactions catalyzed by CYPs, the activities and properties of the many CYPs differ in many aspects. In general, the P450 catalytic cycle proceeds as follows: Substrate binds in proximity to the heme group, on the side opposite to the axial thiolate. Substrate binding induces a change in the conformation of the active site displacing a water molecule from the distal axial coordination position of the heme iron, changing the state of the heme iron from low-spin to high-spin. Substrate binding induces electron transfer from NADH via cytochrome P450 reductase or another associated reductase. Molecular oxygen binds to the resulting ferrous heme center at the distal axial coordination position giving a dioxygen adduct not unlike oxy-myoglobin. A second electron is transferred, from either cytochrome P450 reductase, ferredoxins, or cytochrome b5, reducing the Fe-O2 adduct to give a short-lived peroxo state.
The peroxo group formed in step 4 is protonated twice, releasing one molecule of water and forming the reactive species referred to as P450 Compound 1. This reactive intermediate was isolated in 2010, P450 Compound 1 is an iron oxo species with an additional oxidizing equivalent delocalized over the porphyrin and thiolate ligands. Evidence for the alternative perferryl iron-oxo is lacking. Depending on the substrate and enzyme involved, P450 enzymes can catalyze any of a wide variety of reactions. A hypothetical hydroxylation is shown in this illustration. After the product has been released from the active site, the enzyme returns to its original state, with a water molecule returning to occupy the distal coordination position of the iron nucleus. An alternative route for mono-oxygenation is via the "peroxide shunt"; this pathway entails oxidation of the ferric-substrate complex with oxygen-atom donors such as peroxides and hypochlorites. A hypothetical peroxide "XOOH" is shown in the di
Aspergillus nidulans is one of many species of filamentous fungi in the phylum Ascomycota. It has been an important research organism for studying eukaryotic cell biology for over 50 years, being used to study a wide range of subjects including recombination, DNA repair, cell cycle control, chromatin, pathogenesis and experimental evolution, it is one of the few species in its genus able to form sexual spores through meiosis, allowing crossing of strains in the laboratory. A. nidulans is a homothallic fungus, meaning it is able to self-fertilize and form fruiting bodies in the absence of a mating partner. It has septate hyphae with white mycelia; the green colour of wild-type colonies is due to pigmentation of the spores, while mutations in the pigmentation pathway can produce other spore colours. The A. nidulans genome was sequenced in a collaboration between the Broad Institute. A sequence with 13-fold coverage was publicly released in March 2003, it is 30 million base pairs in size and is predicted to contain around 9,500 protein-coding genes on eight chromosomes.
Several caspase-like proteases were isolated from A. nidulans samples under which programmed cell death had been induced. Findings such as these play a key role in determining the evolutionary conservation of the mitochondrion within the eukaryotic cell, its role as an ancient proteobacterium capable of inducing cell death. Sexual reproduction occurs in two fundamentally different ways; this is by outcrossing, in which two distinct individuals contribute nuclei, or by homothallic sex or self-fertilization in which both nuclei are derived from the same individual. Selfing in A. nidulans involves activation of the same mating pathways characteristic of sex in outcrossing species, i.e. self-fertilization does not bypass required pathways for outcrossing sex but instead requires activation of these pathways within a single individual. Fusion of haploid nuclei occurs within reproductive structures termed “cleistothecia,” in which the diploid zygote undergoes meiotic divisions to yield haploid ascospores.
Anidulafungin is a semisynthetic lipopeptide antifungal drug of echinocandin B subclass, derived from a fermentation product of A. nidulans var. echinulatus strain A 32204, was discovered in Germany in 1974. Aspergillus nidulans genome CADRE Fungal Genetics Stock Center
Echinocandins are a new class of antifungal drugs that inhibit the synthesis of β-glucan in the fungal cell wall via noncompetitive inhibition of the enzyme 1,3-β glucan synthase. The class has been termed the "penicillin of antifungals," along with the related papulacandins, as their mechanism of action resembles that of penicillin in bacteria. Β-glucans are carbohydrate polymers that are cross-linked with other fungal cell wall components, equivalent to bacterial peptidoglycan. Caspofungin and anidulafungin are semisynthetic echinocandin derivatives with clinical use due to their solubility, antifungal spectrum, pharmacokinetic properties. Drugs and drug candidates in this class are fungicidal against some yeasts. Echinocandins have displayed activity against Candida biofilms in synergistic activity with amphotericin B and additive activity with fluconazole. Echinocandins are fungistatic against some molds, modestly or minimally active against dimorphic fungi; these have some activity against the spores of the fungus Pneumocystis jirovecii known as Pneumocystis carinii.
Caspofungin is used in the treatment of febrile neutropenia and as salvage therapy for the treatment of invasive aspergillosis. Micafungin is used as prophylaxis against Candida infections in hematopoietic stem cell transplantation patients. All three agents are well tolerated, with the most common adverse effects being fever, rash and phlebitis at the infusion site, they can cause a histamine-like reaction when infused too rapidly. Toxicity is uncommon, its use has been associated with alkaline phosphatase levels. The present-day clinically used echinocandins are semisynthetic pneumocandins, which are chemically lipopeptide in nature, consisting of large cyclic peptoid. Caspofungin and anidulafungin are similar cyclic hexapeptide antibiotics linked to long modified N-linked acyle fatty acid chains; the chains act. Due to their limited oral bioavailability, echinocandins are administered through intravenous infusion. Echinocandins noncompetitively inhibit beta-1,3-D-glucan synthase enzyme complex in susceptible fungi to disturb fungal cell glucan synthesis.
Beta-glucan destruction prevents resistance against osmotic forces. They have fungistatic activity against Aspergillus species, and fungicidal activity against most Candida spp. including strains that are fluconazole-resistant. In vitro and mouse models show echinocandins may enhance host immune responses by exposing antigenic beta-glucan epitopes that can accelerate host cellular recognition and inflammatory responses. Echinocandin resistance is rare. However, case studies have shown some resistance in C. albicans, C. glabrata, C. lusitaniae, C. tropicalis, C. parapsilosis. Resistance patterns include alterations in the glucan synthase, overexpression of efflux pumps, strengthening of cell wall by increased chitin production, upregulation of stress-response pathways. Due to the large molecular weight of echinocandins, they have poor oral bioavailability and are administered by intravenous infusion. In addition, their large structures limit penetration into cerebrospinal fluid and eyes. In plasma, echinocandins have a high affinity to serum proteins.
Echinocandins do not have primary interactions with P-glycoprotein pumps. Caspofungin has triphasic nonlinear pharmacokinetics, while micafungin and anidulafungin have linear elimination. Younger patients exhibit a faster rate of elimination of caspofungin. Caspofungin has some interference with ciclosporin metabolism, micafungin has some interference with sirolimus, but anidulafungin needs no dose adjustments when given with ciclosporin, tacrolimus, or voriconazole. Advantages of echinocandins: broad range, thus can be given empirically in febrile neutropenia and stem cell transplant can be used in case of azole-resistant Candida or use as a second-line agent for refractory aspergillosis long half-life low toxicity: only histamine release, fever and vomiting, phlebitis at the injection site rarely allergy and anaphylaxis not an inhibitor, inducer, or substrate of the cytochrome P450 system, or P-glycoprotein, thus minimal drug interactions lack of interference from renal failure and hemodialysis no dose adjustment is necessary based on age, race better than amphotericin B and fluconazole against yeast infections Disadvantages of echinocandins: embryotoxic in animal studies thus should be avoided if possible in pregnancy needs dose adjustment in liver disease poor ocular penetration in fungal endophthalmitis List of echinocandins: Pneumocandins Echinocandin B not clinically used, risk of hemolysis Cilofungin withdrawn from trials due to solvent toxicity Caspofungin Micafungin Anidulafungin Rezafungin CD101 IV, Rezafungin is considered to be safest echinocandins which acts longest.
It is developed by Cidara Therapeutics
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.
Aspergillus is a genus consisting of a few hundred mold species found in various climates worldwide. Aspergillus was first catalogued in 1729 by biologist Pier Antonio Micheli. Viewing the fungi under a microscope, Micheli was reminded of the shape of an aspergillum, from Latin spargere, named the genus accordingly. Aspergillum is an asexual spore-forming structure common to all Aspergillus species. Aspergillus consists of a few hundred species. Aspergillus is defined as a group of conidial fungi --; some of them, are known to have a teleomorph in the Ascomycota, so with DNA evidence forthcoming, members of the genus Aspergillus can tentatively be considered members of the Ascomycota. Members of the genus possess the ability to grow. Aspergillus species are aerobic and are found in all oxygen-rich environments, where they grow as molds on the surface of a substrate, as a result of the high oxygen tension. Fungi grow on carbon-rich substrates like monosaccharides and polysaccharides. Aspergillus species are common contaminants of starchy foods, grow in or on many plants and trees.
In addition to growth on carbon sources, many species of Aspergillus demonstrate oligotrophy where they are capable of growing in nutrient-depleted environments, or environments with a complete lack of key nutrients. Aspergillus niger is a prime example of this. Aspergillus are found in millions in pillows. Species of Aspergillus are important medically and commercially; some species can cause infection in other animals. Some infections found in animals have been studied for years, while other species found in animals have been described as new and specific to the investigated disease, others have been known as names in use for organisms such as saprophytes. More than 60 Aspergillus species are medically relevant pathogens. For humans, a range of diseases such as infection to the external ear, skin lesions, ulcers classed as mycetomas are found. Other species are important in commercial microbial fermentations. For example, alcoholic beverages such as Japanese sake are made from rice or other starchy ingredients, rather than from grapes or malted barley.
Typical microorganisms used to make alcohol, such as yeasts of the genus Saccharomyces, cannot ferment these starches. Therefore, koji mold such as Aspergillus oryzae is used to first break down the starches into simpler sugars. Members of the genus are sources of natural products that can be used in the development of medications to treat human disease; the largest application of Aspergillus niger is as the major source of citric acid. A. niger is commonly used for the production of native and foreign enzymes, including glucose oxidase and lactase. In these instances, the culture is grown on a solid substrate, although this is still common practice in Japan, but is more grown as a submerged culture in a bioreactor. In this way, the most important parameters can be controlled, maximal productivity can be achieved; this process makes it far easier to separate the chemical or enzyme of importance from the medium, is therefore far more cost-effective. A. nidulans has been used as a research organism for many years and was used by Guido Pontecorvo to demonstrate parasexuality in fungi.
A. nidulans was one of the pioneering organisms to have its genome sequenced by researchers at the Broad Institute. As of 2008, a further seven Aspergillus species have had their genomes sequenced: the industrially useful A. niger, A. oryzae, A. terreus, the pathogens A. clavatus, A. fischerianus, A. flavus, A. fumigatus. A. fischerianus is hardly pathogenic, but is closely related to the common pathogen A. fumigatus. Of the 250 species of aspergilli, about 64% have no known sexual state. However, many of these species have an as yet unidentified sexual stage. Sexual reproduction occurs in two fundamentally different ways in fungi; these are outcrossing in which two different individuals contribute nuclei, self-fertilization or selfing in which both nuclei are derived from the same individual. In recent years, sexual cycles have been discovered in numerous species thought to be asexual; these discoveries reflect recent experimental focus on species of particular relevance to humans. A. fumigatus is the most common species to cause disease in immunodeficient humans.
In 2009, A. fumigatus was shown to have a heterothallic functional sexual cycle. Isolates of complementary mating types are required for sex to occur. A. flavus is the major producer of carcinogenic aflatoxins in crops worldwide. It is an opportunistic human and animal pathogen, causing aspergillosis in immunocompromised individuals. In 2009, a sexual state of this heterothallic fungus was found to arise when strains of opposite mating types were cultured together under appropriate conditions. A. Lentulus is an opportunistic human pathogen that causes invasive aspergillosis with high mortality rates. In 2013, A. lentulus was found to have a heterothallic functional sexual breeding system. A. Terreus is co
Excretion is a process by which metabolic waste is eliminated from an organism. In vertebrates this is carried out by the lungs and skin; this is in contrast with secretion, where the substance may have specific tasks after leaving the cell. Excretion is an essential process in all forms of life. For example, in mammals urine is expelled through the urethra, part of the excretory system. In unicellular organisms, waste products are discharged directly through the surface of the cell. During life activities such as cellular respiration, several chemical reactions take place in the body; these are known as metabolism. These chemical reactions produce waste products such as carbon dioxide, salts and uric acid. Accumulation of these wastes beyond a level inside the body is harmful to the body; the excretory organs remove these wastes. This process of removal of metabolic waste from the body is known as excretion. Green plants produce carbon water as respiratory products. In green plants, the carbon dioxide released during respiration gets utilized during photosynthesis.
Oxygen is a by product generated during photosynthesis, exits through stomata, root cell walls, other routes. Plants can get rid of excess water by guttation, it has been shown that the leaf acts as an'excretophore' and, in addition to being a primary organ of photosynthesis, is used as a method of excreting toxic wastes via diffusion. Other waste materials that are exuded by some plants — resin, latex, etc. are forced from the interior of the plant by hydrostatic pressures inside the plant and by absorptive forces of plant cells. These latter processes do not need added energy, they act passively. However, during the pre-abscission phase, the metabolic levels of a leaf are high. Plants excrete some waste substances into the soil around them. In animals, the main excretory products are carbon dioxide, urea, uric acid and creatine; the liver and kidneys clear many substances from the blood, the cleared substances are excreted from the body in the urine and feces. Aquatic animals excrete ammonia directly into the external environment, as this compound has high solubility and there is ample water available for dilution.
In terrestrial animals ammonia-like compounds are converted into other nitrogenous materials as there is less water in the environment and ammonia itself is toxic. Birds excrete their nitrogenous wastes as uric acid in the form of a paste. Although this process is metabolically more expensive, it allows more efficient water retention and it can be stored more in the egg. Many avian species seabirds, can excrete salt via specialized nasal salt glands, the saline solution leaving through nostrils in the beak. In insects, a system involving Malpighian tubules is utilized to excrete metabolic waste. Metabolic waste diffuses or is transported into the tubule, which transports the wastes to the intestines; the metabolic waste is released from the body along with fecal matter. The excreted material may be called ejecta. In pathology the word ejecta is more used. UAlberta.ca, Animation of excretion Brian J Ford on leaf fall in Nature
Feces are the solid or semisolid remains of the food that could not be digested in the small intestine. Bacteria in the large intestine further break down the material. Feces contain a small amount of metabolic waste products such as bacterially altered bilirubin, the dead epithelial cells from the lining of the gut. Feces are discharged through cloaca during a process called defecation. Feces can be used as soil conditioner in agriculture, it can be burned and used as a fuel source or dried and used as a construction material. Some medicinal uses have been found. In the case of human feces, fecal transplants or fecal bacteriotherapy are in use. Urine and feces together are called excreta; the distinctive odor of feces is due to bacterial action. Gut flora produces compounds such as indole and thiols, as well as the inorganic gas hydrogen sulfide; these are the same compounds. Consumption of foods prepared with spices may result in the spices being undigested and adding to the odor of feces; the perceived bad odor of feces has been hypothesized to be a deterrent for humans, as consuming or touching it may result in sickness or infection.
Human perception of the odor may be contrasted by a non-human animal's perception of it. Feces are discharged through cloaca during a process called defecation; this process requires pressures that may reach 100 mm Hg in 450 mm Hg in penguins. The forces required to expel the feces are generated through muscular contractions and a build-up of gases inside the gut, prompting the sphincter to relieve the pressure on it and to release the feces. After an animal has digested eaten material, the remains of that material are discharged from its body as waste. Although it is lower in energy than the food from which it is derived, feces may retain a large amount of energy 50% of that of the original food; this means that of all food eaten, a significant amount of energy remains for the decomposers of ecosystems. Many organisms feed on feces, from bacteria to fungi to insects such as dung beetles, who can sense odors from long distances; some may specialize in feces. Feces serve not only as a basic food, but as a supplement to the usual diet of some animals.
This process is known as coprophagia, occurs in various animal species such as young elephants eating the feces of their mothers to gain essential gut flora, or by other animals such as dogs and monkeys. Feces and urine, which reflect ultraviolet light, are important to raptors such as kestrels, who can see the near ultraviolet and thus find their prey by their middens and territorial markers. Seeds may be found in feces. Animals who eat fruit are known as frugivores. An advantage for a plant in having fruit is that animals will eat the fruit and unknowingly disperse the seed in doing so; this mode of seed dispersal is successful, as seeds dispersed around the base of a plant are unlikely to succeed and are subject to heavy predation. Provided the seed can withstand the pathway through the digestive system, it is not only to be far away from the parent plant, but is provided with its own fertilizer. Organisms that subsist on dead organic matter or detritus are known as detritivores, play an important role in ecosystems by recycling organic matter back into a simpler form that plants and other autotrophs may absorb once again.
This cycling of matter is known as the biogeochemical cycle. To maintain nutrients in soil it is therefore important that feces return to the area from which they came, not always the case in human society where food may be transported from rural areas to urban populations and feces disposed of into a river or sea. Depending on the individual and the circumstances, human beings may defecate several times a day, every day, or once every two or three days; the extensive hardening that interrupts this routine for several days or more is called constipation. The appearance of human fecal matter varies according to health, it is semisolid, with a mucus coating. A combination of bile and bilirubin, which comes from dead red blood cells, gives feces the typical brown color. After the meconium, the first stool expelled, a newborn's feces contain only bile, which gives it a yellow-green color. Breast feeding babies expel soft, pale yellowish, not quite malodorous matter. At different times in their life, human beings will expel feces of different textures.
A stool that passes through the intestines will look greenish. The feces of animals are used as fertilizer. Dry animal dung is used as a fuel source in many countries around the world; some animal feces that of camel and cattle, are fuel sources when dried. Animals such as the giant panda and zebra possess gut bacteria capable of producing biofuel; that bacteria, called Brocadia anammoxidans, can create the rocket fuel hydrazine. A coprolite is classified as a trace fossil. In paleontology they give evidence about the diet of an animal, they were first described by William Buckland in 1829. Prior to this they were known as "fossil fir cones" and "bezoar stones", they serve a valuable purpose in paleontology because they provide direct evidence of the predation and diet of extinct organisms. Coprolites may range in size from a few millimetres to more than 60 centimetres. Palaeofeces are ancie