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BACE1-AS
''BACE1-AS'', also known as BACE1 antisense RNA ( non-protein coding), is a human gene at 11q23.3 encoding a long noncoding RNA molecule. It is transcribed from the opposite strand to ''BACE1'' and is upregulated in patients with Alzheimer's disease. BACE1-AS regulates the expression of BACE1 by increasing BACE1 mRNA stability and generating additional BACE1 through a post-transcriptional feed-forward mechanism. By the same mechanism it also raises concentrations of beta amyloid, the main constituent of senile plaques. BACE1-AS concentrations are elevated in subjects with Alzheimer's disease and in amyloid precursor protein transgenic mice A genetically modified mouse or genetically engineered mouse model (GEMM) is a mouse (''Mus musculus'') that has had its genome altered through the use of genetic engineering techniques. Genetically modified mice are commonly used for research or .... Knocking down BACE1-AS reduces amyloid production and plaque deposition. References E ...
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Non-coding RNA
A non-coding RNA (ncRNA) is a functional RNA molecule that is not translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally important types of non-coding RNAs include transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), as well as small RNAs such as microRNAs, siRNAs, piRNAs, snoRNAs, snRNAs, exRNAs, scaRNAs and the long ncRNAs such as Xist and HOTAIR. The number of non-coding RNAs within the human genome is unknown; however, recent transcriptomic and bioinformatic studies suggest that there are thousands of non-coding transcripts. Many of the newly identified ncRNAs have not been validated for their function. There is no consensus in the literature on how much of non-coding transcription is functional. Some researchers have argued that many ncRNAs are non-functional (sometimes referred to as "junk RNA"), spurious transcriptions. Others, however, disagree, arguing instead ...
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Human
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, and language. Humans are highly social and tend to live in complex social structures composed of many cooperating and competing groups, from families and kinship networks to political states. Social interactions between humans have established a wide variety of values, social norms, and rituals, which bolster human society. Its intelligence and its desire to understand and influence the environment and to explain and manipulate phenomena have motivated humanity's development of science, philosophy, mythology, religion, and other fields of study. Although some scientists equate the term ''humans'' with all members of the genus ''Homo'', in common usage, it generally refers to ''Homo sapiens'', the only Extant taxon, extant member. A ...
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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 g ...
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Long Noncoding RNA
Long non-coding RNAs (long ncRNAs, lncRNA) are a type of RNA, generally defined as transcripts more than 200 nucleotides that are not translated into protein. This arbitrary limit distinguishes long ncRNAs from small non-coding RNAs, such as microRNAs (miRNAs), small interfering RNAs (siRNAs), Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), and other short RNAs. Long intervening/intergenic noncoding RNAs (lincRNAs) are sequences of lncRNA which do not overlap protein-coding genes. Long non-coding RNAs include intergenic lincRNAs, intronic ncRNAs, and sense and antisense lncRNAs, each type showing different genomic positions in relation to genes and exons. Abundance In 2007 a study found only one-fifth of transcription across the human genome is associated with protein-coding genes, indicating at least four times more long non-coding than coding RNA sequences. Large-scale complementary DNA (cDNA) sequencing projects such as FANTOM reveal the complexity of this ...
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Beta-secretase 1
Beta-secretase 1, also known as beta-site amyloid precursor protein cleaving enzyme 1, beta-site APP cleaving enzyme 1 (BACE1), membrane-associated aspartic protease 2, memapsin-2, aspartyl protease 2, and ASP2, is an enzyme that in humans is encoded by the ''BACE1'' gene. Expression of BACE1 is observed mainly in neurons. BACE1 is an aspartic acid protease important in the formation of myelin sheaths in peripheral nerve cells: in mice the expression of BACE1 is high in the postnatal stages, when myelination occurs. * The transmembrane protein contains two active site aspartate residues in its extracellular protein domain and may function as a dimer, its cytoplasmic tail is required for the correct maturation and an efficient intracellular trafficking, but doesn't affect the activity. It is produced as a pro-enzyme, the endoproteolitc removal occurs after BACE leaves Endoplasmic reticulum, in the Golgi apparatus. In addition the pro-peptide receives additional sugars to increase ...
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Alzheimer's Disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term memory, remembering recent events. As the disease advances, symptoms can include primary progressive aphasia, problems with language, Orientation (mental), disorientation (including easily getting lost), mood swings, loss of motivation, self-neglect, and challenging behaviour, behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the typical life expectancy following diagnosis is three to nine years. The cause of Alzheimer's disease is poorly understood. There are many environmental and genetic risk factors associated with its development. The strongest genetic risk factor is from an alle ...
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Gene Expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. These products are often proteins, but in non-protein-coding genes such as transfer RNA (tRNA) and small nuclear RNA (snRNA), the product is a functional non-coding RNA. Gene expression is summarized in the central dogma of molecular biology first formulated by Francis Crick in 1958, further developed in his 1970 article, and expanded by the subsequent discoveries of reverse transcription and RNA replication. The process of gene expression is used by all known life— eukaryotes (including multicellular organisms), prokaryotes (bacteria and archaea), and utilized by viruses—to generate the macromolecular machinery for life. In genetics, gene expression is the most fundamental level at which the genotype gives rise to the phen ...
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Feed Forward (control)
A feed forward (sometimes written feedforward) is an element or pathway within a control system that passes a controlling signal from a source in its external environment to a load elsewhere in its external environment. This is often a command signal from an external operator. A control system which has only feed-forward behavior responds to its control signal in a pre-defined way without responding to the way the load reacts; it is in contrast with a system that also has feedback, which adjusts the input to take account of how it affects the load, and how the load itself may vary unpredictably; the load is considered to belong to the external environment of the system. In a feed-forward system, the control variable adjustment is not error-based. Instead it is based on knowledge about the process in the form of a mathematical model of the process and knowledge about, or measurements of, the process disturbances. Some prerequisites are needed for control scheme to be reliable ...
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Beta Amyloid
Beta (, ; uppercase , lowercase , or cursive ; grc, βῆτα, bē̂ta or ell, βήτα, víta) is the second letter of the Greek alphabet. In the system of Greek numerals, it has a value of 2. In Modern Greek, it represents the voiced labiodental fricative while in borrowed words is instead commonly transcribed as μπ. Letters that arose from beta include the Roman letter and the Cyrillic letters and . Name Like the names of most other Greek letters, the name of beta was adopted from the acrophonic name of the corresponding letter in Phoenician, which was the common Semitic word ''*bait'' ('house'). In Greek, the name was ''bêta'', pronounced in Ancient Greek. It is spelled βήτα in modern monotonic orthography and pronounced . History The letter beta was derived from the Phoenician letter beth . Uses Algebraic numerals In the system of Greek numerals, beta has a value of 2. Such use is denoted by a number mark: Β′. Computing Finance Beta is used in ...
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Senile Plaque
Amyloid plaques (also known as neuritic plaques, amyloid beta plaques or senile plaques) are extracellular deposits of the amyloid beta (Aβ) protein mainly in the grey matter of the brain. Degenerative neuronal elements and an abundance of microglia and astrocytes can be associated with amyloid plaques. Some plaques occur in the brain as a result of aging, but large numbers of plaques and neurofibrillary tangles are characteristic features of Alzheimer's disease. Abnormal neurites in amyloid plaques are tortuous, often swollen axons and dendrites. The neurites contain a variety of organelles and cellular debris, and many of them include characteristic paired helical filaments, the ultrastructural component of neurofibrillary tangles. The plaques are highly variable in shape and size; in tissue sections immunostained for Aβ, they comprise a log-normal size distribution curve with an average plaque area of 400-450 square micrometers (µm²). The smallest plaques (less than ...
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Amyloid
Amyloids are aggregates of proteins characterised by a fibrillar morphology of 7–13 nm in diameter, a beta sheet (β-sheet) secondary structure (known as cross-β) and ability to be stained by particular dyes, such as Congo red. In the human body, amyloids have been linked to the development of various diseases. Pathogenic amyloids form when previously healthy proteins lose their normal structure and physiological functions ( misfolding) and form fibrous deposits in amyloid plaques around cells which can disrupt the healthy function of tissues and organs. Such amyloids have been associated with (but not necessarily as the cause of) more than 50 human diseases, known as amyloidosis, and may play a role in some neurodegenerative diseases. Some of these diseases are mainly sporadic and only a few cases are familial. Others are only familial. Some are iatrogenic as they result from medical treatment. Prions are an infectious form of amyloids that can act as a template ...
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Transgenic Mice
A genetically modified mouse or genetically engineered mouse model (GEMM) is a mouse (''Mus musculus'') that has had its genome altered through the use of genetic engineering techniques. Genetically modified mice are commonly used for research or as animal models of human diseases, and are also used for research on genes. Together with patient-derived xenografts (PDXs), GEMMs are the most common '' in vivo'' models in cancer research. Both approaches are considered complementary and may be used to recapitulate different aspects of disease. GEMMs are also of great interest for drug development, as they facilitate target validation and the study of response, resistance, toxicity and pharmacodynamics. History In 1974 Beatrice Mintz and Rudolf Jaenisch created the first genetically modified animal by inserting a DNA virus into an early-stage mouse embryo and showing that the inserted genes were present in every cell. However, the mice did not pass the transgene to their offspring ...
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