Instruct: Given a question, retrieve passages that answer the question.
Query: Who first identified the process of autophagy?
Christian de Duve coined the term autophagy in 1963 whereas Ohsumi began his work in 1988. Prior to that time, less than 20 papers per year were published on this subject. During the 1990s, Ohsumi's group described the morphology of autophagy in yeast, and performed mutational screening on yeast cells that identified essential genes for cells to be capable of autophagy.
The field of oxidative phosphorylation began with the report in 1906 by Arthur Harden of a vital role for phosphate in cellular fermentation, but initially only sugar phosphates were known to be involved. However, in the early 1940s, the link between the oxidation of sugars and the generation of ATP was firmly established by Herman Kalckar, confirming the central role of ATP in energy transfer that had been proposed by Fritz Albert Lipmann in 1941. Later, in 1949, Morris Friedkin and Albert L. Lehninger proved that the coenzyme NADH linked metabolic pathways such as the citric acid cycle and the synthesis of ATP. The term "oxidative phosphorylation" was coined by in 1939.
In October 2001, Cuervo accepted a faculty position at the Albert Einstein College of Medicine in The Bronx, New York. She then began primarily focusing on chaperone-mediated autophagy and its role in aging and human disease. Her research lab focused on protein translocations across lysosomal membranes, identifying regulator proteins like glial fibrillary acidic protein. In collaboration with neuroscientist David Sulzer of Columbia University Medical Center, she published evidence of altered chaperone-mediated autophagy in Parkinson's Disease. Similar findings of disrupted autophagy was also reported when Huntington Disease was studied. Cuervo's research team also identified LRRK2, a protein enzyme that becomes mutated in Parkinson's disease, disrupts the process of translocation across lysosomal membranes.
In biology, cell theory is the historic scientific theory, now universally accepted, that living organisms are made up of cells, that they are the basic structural/organizational unit of all organisms, and that all cells come from pre-existing cells. Cells are the basic unit of structure in all organisms and also the basic unit of reproduction. With continual improvements made to microscopes over time, magnification technology advanced enough to discover cells in the 17th century. This discovery is largely attributed to Robert Hooke, and began the scientific study of cells, also known as cell biology. Over a century later, many debates about cells began amongst scientists. Most of these debates involved the nature of cellular regeneration, and the idea of cells as a fundamental unit of life. Cell theory was eventually formulated in 1839. This is usually credited to Matthias Schleiden and Theodor Schwann. However, many other scientists like Rudolf Virchow contributed to the theory. It was an important step in the movement away from spontaneous generation.
In eukaryotes, the enzymes in this electron transport system use the energy released from the oxidation of NADH to pump protons across the inner membrane of the mitochondrion. This causes protons to build up in the intermembrane space, and generates an electrochemical gradient across the membrane. The energy stored in this potential is then used by ATP synthase to produce ATP. Oxidative phosphorylation in the eukaryotic mitochondrion is the best-understood example of this process. The mitochondrion is present in almost all eukaryotes, with the exception of anaerobic protozoa such as "Trichomonas vaginalis" that instead reduce protons to hydrogen in a remnant mitochondrion called a hydrogenosome.
In August 1961, at the International Congress of Biochemistry in Moscow, Nirenberg presented his paper. The experimentation with synthetic RNA in a cell-free system was a key technical innovation. In 1961, when they announced their methods for decoding the relationship of mRNA to amino acids, there was still a lot of experimentation required before the entire code was deciphered. The scientists had to determine which bases made up each codon, then determine the sequence of bases in the codons. This proved to be a tremendous amount of work.
"mazEF", a toxin-antitoxin locus found in "E. coli" and other bacteria, was proposed to induce programmed cell death in response to starvation, specifically a lack of amino acids. This would release the cell's contents for absorption by neighbouring cells, potentially preventing the death of close relatives, and thereby increasing the inclusive fitness of the cell that perished. This would be an example of altruism and how bacterial colonies could resemble multicellular organisms. However, the ""mazEF"-mediated PCD" has largely been refuted by several studies.
Credit for developing cell theory is usually given to two scientists: Theodor Schwann and Matthias Jakob Schleiden. While Rudolf Virchow contributed to the theory, he is not as credited for his attributions toward it. In 1839, Schleiden suggested that every structural part of a plant was made up of cells or the result of cells. He also suggested that cells were made by a crystallization process either within other cells or from the outside. However, this was not an original idea of Schleiden. He claimed this theory as his own, though Barthelemy Dumortier had stated it years before him. This crystallization process is no longer accepted with modern cell theory. In 1839, Theodor Schwann states that along with plants, animals are composed of cells or the product of cells in their structures. This was a major advancement in the field of biology since little was known about animal structure up to this point compared to plants. From these conclusions about plants and animals, two of the three tenets of cell theory were postulated.
Extracellular digestion is a process in which saprobionts feed by secreting enzymes through the cell membrane onto the food. The enzymes catalyze the digestion of the food into molecules small enough to be taken up by passive diffusion, transport, or phagocytosis. Since digestion occurs outside the cell, it is said to be extracellular. It takes place either in the lumen of the digestive system, in a gastric cavity or other digestive organ, or completely outside the body.
The discovery of a role for the pancreas in diabetes is generally ascribed to Joseph von Mering and Oskar Minkowski, who in 1889 found that dogs whose pancreas was removed developed all the signs and symptoms of diabetes and died shortly afterwards. In 1910, Sir Edward Albert Sharpey-Schafer suggested that people with diabetes were deficient in a single chemical that was normally produced by the pancreas—he proposed calling this substance insulin, from the Latin "insula", meaning island, in reference to the insulin-producing islets of Langerhans in the pancreas. The endocrine role of the pancreas in metabolism, and indeed the existence of insulin, was further clarified in 1921, when Sir Frederick Grant Banting and Charles Herbert Best repeated the work of Von Mering and Minkowski, and went further to demonstrate they could reverse induced diabetes in dogs by giving them an extract from the pancreatic islets of Langerhans of healthy dogs. The islets of Langerhans was discovered in 1869 by an anatomist named Paul Langerhans. He identified the keys cells in the pancreas which produce the main substance that controls glucose levels in the body.
Cell, developmental, and reproductive biology have been a central part of the MBL's programs since the 1890s. Important discoveries in these fields at the MBL reach back to 1899, when Jacques Loeb demonstrated artificial parthenogenesis in sea urchin eggs; to 1905, when Edwin Grant Conklin first identified egg cytoplasmic regions that are programmed to form certain tissues or organs; to 1916, when Frank Rattray Lillie identified circulating hormones that influence sexual differentiation (Lillie, 1944). In the MBL's first two decades, cytologists Edmund Beecher Wilson, Nettie Stevens and others made connections between the chromosomes and Mendelian heredity, while Wilson's colleague at both the MBL and Columbia University, Thomas Hunt Morgan, launched the field of experimental genetics (Pauly, 2000:158). Keith R. Porter, considered by many to be a founder of modern cell biology due to his pioneering work on the fine structure of cells, including the discovery of microtubules, carried out research at the MBL starting in 1937 and directed the laboratory from 1975-77 (Barlow et al., 1993: 95-115).
In biochemistry and metabolism, beta-oxidation is the catabolic process by which fatty acid molecules are broken down in the cytosol in prokaryotes and in the mitochondria in eukaryotes to generate acetyl-CoA, which enters the citric acid cycle, and NADH and FADH, which are co-enzymes used in the electron transport chain. It is named as such because the beta carbon of the fatty acid undergoes oxidation to a carbonyl group. Beta-oxidation is primarily facilitated by the mitochondrial trifunctional protein, an enzyme complex associated with the inner mitochondrial membrane, although very long chain fatty acids are oxidized in peroxisomes.
Mitochondrial DNA was discovered in the 1960s by Margit M. K. Nass and Sylvan Nass by electron microscopy as DNase-sensitive threads inside mitochondria, and by Ellen Haslbrunner, Hans Tuppy and Gottfried Schatz by biochemical assays on highly purified mitochondrial fractions.
Major Alfred Whitmore (1876–1946) was an English pathologist who, together with C.S. Krishnaswami, identified "Burkholderia pseudomallei", the causative agent of melioidosis (also known as "Whitmore's disease") in opium addicts in Rangoon in 1911. He differentiated it from "Burkholderia mallei", the causative agent of glanders, by clinical and microbiological features.
The New Latin word "autismus" (English translation "autism") was coined by the Swiss psychiatrist Eugen Bleuler in 1910 as he was defining symptoms of schizophrenia. He derived it from the Greek word "autós" (αὐτός, meaning "self"), and used it to mean morbid self-admiration, referring to "autistic withdrawal of the patient to his fantasies, against which any influence from outside becomes an intolerable disturbance". A Soviet child psychiatrist, Grunya Sukhareva, described a similar syndrome that was published in Russian in 1925, and in German in 1926.
Secretin was the first hormone to be identified. In 1902, William Bayliss and Ernest Starling were studying how the nervous system controls the process of digestion. It was known that the pancreas secreted digestive juices in response to the passage of food (chyme) through the pyloric sphincter into the duodenum. They discovered (by cutting all the nerves to the pancreas in their experimental animals) that this process was not, in fact, governed by the nervous system. They determined that a substance secreted by the intestinal lining stimulates the pancreas after being transported via the bloodstream. They named this intestinal secretion "secretin". Secretin was the first such "chemical messenger" identified. This type of substance is now called a hormone, a term coined by Bayliss in 1905.
Michigan State University, Kellogg Biological Station: Eminent Ecologist (1992)
The history of biochemistry can be said to have started with the ancient Greeks who were interested in the composition and processes of life, although biochemistry as a specific scientific discipline has its beginning around the early 19th century. Some argued that the beginning of biochemistry may have been the discovery of the first enzyme, diastase (today called amylase), in 1833 by Anselme Payen, while others considered Eduard Buchner's first demonstration of a complex biochemical process alcoholic fermentation in cell-free extracts to be the birth of biochemistry. Some might also point to the influential work of Justus von Liebig from 1842, "Animal chemistry, or, Organic chemistry in its applications to physiology and pathology", which presented a chemical theory of metabolism, or even earlier to the 18th century studies on fermentation and respiration by Antoine Lavoisier.
The first model known as the "syntrophic model" proposes that a symbiotic relationship between the archaea and bacteria created the nucleus-containing eukaryotic cell. (Organisms of the Archaea and Bacteria domain have no cell nucleus.) It is hypothesized that the symbiosis originated when ancient archaea, similar to modern methanogenic archaea, invaded and lived within bacteria similar to modern myxobacteria, eventually forming the early nucleus. This theory is analogous to the accepted theory for the origin of eukaryotic mitochondria and chloroplasts, which are thought to have developed from a similar endosymbiotic relationship between proto-eukaryotes and aerobic bacteria. The archaeal origin of the nucleus is supported by observations that archaea and eukarya have similar genes for certain proteins, including histones. Observations that myxobacteria are motile, can form multicellular complexes, and possess kinases and G proteins similar to eukarya, support a bacterial origin for the eukaryotic cell.
Anselme Payen discovered in 1833 the first enzyme who called diastase and in 1878 German physiologist Wilhelm Kühne (1837–1900) coined the term "enzyme", which comes from Greek "ενζυμον" "in leaven", to describe this process. The word "enzyme" was used later to refer to nonliving substances such as pepsin, and the word "ferment" used to refer to chemical activity produced by living organisms.
The Greek physician Hippocrates, the founder of scientific medicine, was the first to deal with the anatomy and the pathology of human spine. Galen developed an interest in anatomy from his studies of Herophilus and Erasistratus. The concept of studying disease through the methodical dissection and examination of diseased bodies, organs, and tissues may seem obvious today, but there are few if any recorded examples of true autopsies performed prior to the second millennium. Though the pathology of contagion was understood by Muslim physicians since the time of Avicenna (980–1037) who described it in "The Canon of Medicine" (c. 1020), the first physician known to have made postmortem dissections was the Arabian physician Avenzoar (1091–1161) who proved that the skin disease scabies was caused by a parasite, followed by Ibn al-Nafis (b. 1213) who used dissection to discover pulmonary circulation in 1242. In the 15th century, anatomic dissection was repeatedly used by the Italian physician Antonio Benivieni (1443-1502) to determine cause of death. Antonio Benivieni is also credited with having introduced necropsy to the medical field. Perhaps the most famous early gross pathologist was Giovanni Morgagni (1682-1771). His magnum opus, "De Sedibus et Causis Morborum per Anatomem Indagatis", published in 1761, describes the findings of over 600 partial and complete autopsies, organised anatomically and methodically correlated with the symptoms exhibited by the patients prior to their demise. Although the study of normal anatomy was already well advanced at this date, "De Sedibus" was one of the first treatises specifically devoted to the correlation of diseased anatomy with clinical illness. By the late 1800s, an exhaustive body of literature had been produced on the gross anatomical findings characteristic of known diseases. The extent of gross pathology research in this period can be epitomized by the work of the Viennese pathologist (originally from Hradec Kralove in the Czech Rep.) Carl Rokitansky (1804-1878), who is said to have performed 20,000 autopsies, and supervised an additional 60,000, in his lifetime.
The field of autophagy research experienced accelerated growth at the turn of the 21st century. Knowledge of ATG genes provided scientists more convenient tools to dissect functions of autophagy in human health and disease. In 1999, a landmark discovery connecting autophagy with cancer was published by Beth Levine's group. To this date, relationship between cancer and autophagy continues to be a main theme of autophagy research. The roles of autophagy in neurodegeneration and immune defense also received considerable attention. In 2003, the first Gordon Research Conference on autophagy was held at Waterville. In 2005, Daniel J Klionsky launched "Autophagy", a scientific journal dedicated to this field. The first Keystone Symposia Conference on autophagy was held in 2007 at Monterey. In 2008, Carol A Mercer created a BHMT fusion protein (GST-BHMT), which showed starvation-induced site-specific fragmentation in cell lines. The degradation of betaine homo-cysteine methyltransferase (BHMT), a metabolic enzyme, could be used to assess autophagy flux in mammalian cells.
Autophagy (Greek: ‘self-eating’) was initially identified as a catabolic process for the unselective degradation of cellular content in lysosomes under starvation conditions. However, autophagy also comprises selective degradation pathways, which depend on ubiquitin conjugation to initiate sorting to lysosomes. In the case of chaperone-assisted selective autophagy, dysfunctional, nonnative proteins are recognized by molecular chaperones and become ubiquitinated by chaperone-associated ubiquitin ligases. The ubiquitinated proteins are enclosed in autophagosomes, which eventually fuse with lysosomes, leading to the degradation of the dysfunctional proteins. Chaperone-assisted selective autophagy is a vital part of the cellular protein quality control system. It is essential for protein homeostasis (proteostasis) in neurons and in mechanically strained cells and tissues such as skeletal muscle, heart and lung.
The first autophagy genes were identified by genetic screens conducted in "Saccharomyces cerevisiae". Following their identification those genes were functionally characterized and their orthologs in a variety of different organisms were identified and studied.
Autophagy is the process by which the cells in an organism destroy non-functional or unnecessary self-components. Specifically, autophagy is a catabolic process involving the degradation of a cell's own components through the lysosomal machinery. Autophagy is also crucial for instances of starvation and removal of potentially dangerous cellular materials, indicating its necessity in maintaining life. As seen in the associated figure "Autophagy", cellular products are degraded by destructive cellular components, such as lysosomes, to produce new materials for the cell to use. Research into autophagy and its related processes has exploded over recent years, however, many of these processes processes are not completely understood and homologs have not been found in different species for many of these proteins. Its molecular mechanisms have not been fully elucidated, despite dramatic advances in the field as evidenced by hundreds of autophagy-related genes and proteins reported. As such, there was a demonstrated need for a database to characterize human autophagy proteins and components and/or their homologs, as well as orthologs in other species.