Falkow's Criteria
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Falkow's Criteria
Molecular Koch's postulates are a set of experimental criteria that must be satisfied to show that a gene found in a pathogenic microorganism encodes a product that contributes to the disease caused by the pathogen. Genes that satisfy molecular Koch's postulates are often referred to as virulence factors. The postulates were formulated by the microbiologist Stanley Falkow in 1988 and are based on Koch's postulates. As per Falkow's original descriptions, the three postulates are: # "The phenotype or property under investigation should be associated with pathogenic members of a genus or pathogenic strains of a species. # Specific inactivation of the gene(s) associated with the suspected virulence trait should lead to a measurable loss in pathogenicity or virulence. # Reversion or allelic replacement of the mutated gene should lead to restoration of pathogenicity." To apply the molecular Koch's postulates to human diseases, researchers must identify which microbial genes are potential ...
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Gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a basic unit of heredity and the molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and noncoding genes. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic traits. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes (many different genes) as well as gen ...
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Transcription (biology)
Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules called non-coding RNAs (ncRNAs). mRNA comprises only 1–3% of total RNA samples. Less than 2% of the human genome can be transcribed into mRNA ( Human genome#Coding vs. noncoding DNA), while at least 80% of mammalian genomic DNA can be actively transcribed (in one or more types of cells), with the majority of this 80% considered to be ncRNA. Both DNA and RNA are nucleic acids, which use base pairs of nucleotides as a complementary language. 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 ...
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Microbiology
Microbiology () is the scientific study of microorganisms, those being unicellular (single cell), multicellular (cell colony), or acellular (lacking cells). Microbiology encompasses numerous sub-disciplines including virology, bacteriology, protistology, mycology, immunology, and parasitology. Eukaryotic microorganisms possess membrane-bound organelles and include fungi and protists, whereas prokaryotic organisms—all of which are microorganisms—are conventionally classified as lacking membrane-bound organelles and include Bacteria and Archaea. Microbiologists traditionally relied on culture, staining, and microscopy. However, less than 1% of the microorganisms present in common environments can be cultured in isolation using current means. Microbiologists often rely on molecular biology tools such as DNA sequence based identification, for example the 16S rRNA gene sequence used for bacteria identification. Viruses have been variably classified as organisms, as they have ...
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Epidemiology
Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and determinants of health and disease conditions in a defined population. It is a cornerstone of public health, and shapes policy decisions and evidence-based practice by identifying risk factors for disease and targets for preventive healthcare. Epidemiologists help with study design, collection, and statistical analysis of data, amend interpretation and dissemination of results (including peer review and occasional systematic review). Epidemiology has helped develop methodology used in clinical research, public health studies, and, to a lesser extent, basic research in the biological sciences. Major areas of epidemiological study include disease causation, transmission, outbreak investigation, disease surveillance, environmental epidemiology, forensic epidemiology, occupational epidemiology, screening, biomonitoring, and comparisons of treatment effects such as in clinical trials. ...
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In Situ Hybridization
''In situ'' hybridization (ISH) is a type of hybridization that uses a labeled complementary DNA, RNA or modified nucleic acids strand (i.e., probe) to localize a specific DNA or RNA sequence in a portion or section of tissue (''in situ'') or if the tissue is small enough (e.g., plant seeds, ''Drosophila'' embryos), in the entire tissue (whole mount ISH), in cells, and in circulating tumor cells (CTCs). This is distinct from immunohistochemistry, which usually localizes proteins in tissue sections. In situ hybridization is used to reveal the location of specific nucleic acid sequences on chromosomes or in tissues, a crucial step for understanding the organization, regulation, and function of genes. The key techniques currently in use include ''in situ'' hybridization to mRNA with oligonucleotide and RNA probes (both radio-labeled and hapten-labeled), analysis with light and electron microscopes, whole mount ''in situ'' hybridization, double detection of RNAs and RNA plus prote ...
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Microbial Pathogenesis
Microbial pathogenesis is a field of microbiology started at least as early as 1988, with the identification of the triune Falkow's criteria aka molecular Koch's postulates. In 1996 Fredricks and Relman proposed a seven-point list of "Molecular Guidelines for Establishing Microbial Disease Causation", because of "the discovery of nucleic acids" by Watson and Crick "as the source of genetic information and as the basis for precise characterization of an organism In biology, an organism () is any living system that functions as an individual entity. All organisms are composed of cells ( cell theory). Organisms are classified by taxonomy into groups such as multicellular animals, plants, and fu ...." The subsequent development of the "ability to detect and manipulate these nucleic acid molecules in microorganisms has created a powerful means for identifying previously unknown microbial pathogens and for studying the host-parasite relationship." __TOC__ Postulates for t ...
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Gene Knock-in
In molecular cloning and biology, a gene knock-in (abbreviation: KI) refers to a genetic engineering method that involves the one-for-one substitution of DNA sequence information in a genetic locus or the insertion of sequence information not found within the locus. Typically, this is done in mice since the technology for this process is more refined and there is a high degree of shared sequence complexity between mice and humans. The difference between knock-in technology and traditional transgenic techniques is that a knock-in involves a gene inserted into a specific locus, and is thus a "targeted" insertion. It is the opposite of gene knockout. A common use of knock-in technology is for the creation of disease models. It is a technique by which scientific investigators may study the function of the regulatory machinery (e.g. promoters) that governs the expression of the natural gene being replaced. This is accomplished by observing the new phenotype of the organism in question. T ...
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Gene Knockout
A gene knockout (abbreviation: KO) is a genetic technique in which one of an organism's genes is made inoperative ("knocked out" of the organism). However, KO can also refer to the gene that is knocked out or the organism that carries the gene knockout. Knockout organisms or simply knockouts are used to study gene function, usually by investigating the effect of gene loss. Researchers draw inferences from the difference between the knockout organism and normal individuals. The KO technique is essentially the opposite of a gene knock-in. Knocking out two genes simultaneously in an organism is known as a double knockout (DKO). Similarly the terms triple knockout (TKO) and quadruple knockouts (QKO) are used to describe three or four knocked out genes, respectively. However, one needs to distinguish between heterozygous and homozygous KOs. In the former, only one of two gene copies (alleles) is knocked out, in the latter both are knocked out. Methods Knockouts are accomplished throu ...
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Virulence
Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to cause disease—is determined by its virulence factors. In the specific context of gene for gene systems, often in plants, virulence refers to a pathogen's ability to infect a resistant host. The noun ''virulence'' derives from the adjective ''virulent'', meaning disease severity. The word ''virulent'' derives from the Latin word ''virulentus'', meaning "a poisoned wound" or "full of poison." From an ecological standpoint, virulence is the loss of fitness induced by a parasite upon its host. Virulence can be understood in terms of proximate causes—those specific traits of the pathogen that help make the host ill—and ultimate causes—the evolutionary pressures that lead to virulent traits occurring in a pathogen strain. Virulent ba ...
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Microorganism
A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in older texts. The informal synonym ''microbe'' () comes from μικρός, mikrós, "small" and βίος, bíos, "life". is an organism of microscopic size, which may exist in its single-celled form or as a colony of cells. The possible existence of unseen microbial life was suspected from ancient times, such as in Jain scriptures from sixth century BC India. The scientific study of microorganisms began with their observation under the microscope in the 1670s by Anton van Leeuwenhoek. In the 1850s, Louis Pasteur found that microorganisms caused food spoilage, debunking the theory of spontaneous generation. In the 1880s, Robert Koch discovered that microorganisms caused the diseases tuberculosis, cholera, diphtheria, and anthrax. Because mi ...
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Species
In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriate sexes or mating types can produce fertile offspring, typically by sexual reproduction. Other ways of defining species include their karyotype, DNA sequence, morphology, behaviour or ecological niche. In addition, paleontologists use the concept of the chronospecies since fossil reproduction cannot be examined. The most recent rigorous estimate for the total number of species of eukaryotes is between 8 and 8.7 million. However, only about 14% of these had been described by 2011. All species (except viruses) are given a two-part name, a "binomial". The first part of a binomial is the genus to which the species belongs. The second part is called the specific name or the specific epithet (in botanical nomenclature, also sometimes i ...
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Phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological properties, its behavior, and the products of behavior. An organism's phenotype results from two basic factors: the expression of an organism's genetic code, or its genotype, and the influence of environmental factors. Both factors may interact, further affecting phenotype. When two or more clearly different phenotypes exist in the same population of a species, the species is called polymorphic. A well-documented example of polymorphism is Labrador Retriever coloring; while the coat color depends on many genes, it is clearly seen in the environment as yellow, black, and brown. Richard Dawkins in 1978 and then again in his 1982 book ''The Extended Phenotype'' suggested that one can regard bird nests and other built structures such as cad ...
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