Instruct: Given a question, retrieve relevant passages that answer the question.
Query: How was microglia discovered?
The ability to view and characterize different neural cells including microglia began in 1880 when Nissl staining was developed by Franz Nissl. Franz Nissl and F. Robertson first described microglial cells during their histology experiments. The cell staining techniques in the 1880s showed that microglia are related to macrophages. The activation of microglia and formation of ramified microglial clusters was first noted by Victor Babeş while studying a rabies case in 1897. Babeş noted the cells were found in a variety of viral brain infections but did not know what the clusters of microglia he saw were. Pío del Río Hortega, a student of Santiago Ramón y Cajal, first called the cells "microglia" around 1920. He went on to characterize microglial response to brain lesions in 1927 and note the "fountains of microglia" present in the corpus callosum and other perinatal white matter areas in 1932. After many years of research Rio-Hortega became generally considered as the "Father of Microglia." For a long period of time little improvement was made in our knowledge of microglia. Then, in 1988, Hickey and Kimura showed that perivascular microglial cells are bone-marrow derived, and express high levels of MHC class II proteins used for antigen presentation. This confirmed Pio Del Rio-Hortega's postulate that microglial cells functioned similarly to macrophages by performing phagocytosis and antigen presentation.
This implied neuroplasticity during the critical period. However, Merzenich argued that neuroplasticity could occur beyond the critical period. His first encounter with adult plasticity came when he was engaged in a postdoctoral study with Clinton Woosley. The experiment was based on observation of what occurred in the brain when one peripheral nerve was cut and subsequently regenerated. The two scientists micromapped the hand maps of monkey brains before and after cutting a peripheral nerve and sewing the ends together. Afterwards, the hand map in the brain that they expected to be jumbled was nearly normal. This was a substantial breakthrough. Merzenich asserted that, "If the brain map could normalize its structure in response to abnormal input, the prevailing view that we are born with a hardwired system had to be wrong. The brain had to be plastic." Merzenich received the 2016 Kavli Prize in Neuroscience "for the discovery of mechanisms that allow experience and neural activity to remodel brain function."
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.
The cells were first observed by Karl Wilhelm von Kupffer in 1876. The scientist called them "Sternzellen" (star cells or hepatic stellate cell) but thought, inaccurately, that they were an integral part of the endothelium of the liver blood vessels and that they originated from it. In 1898, after several years of research, Tadeusz Browicz identified them, correctly, as macrophages.
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).
A French Army physician Charles Louis Alphonse Laveran discovered that malaria was caused by microscopic parasite (now called "Plasmodium falciparum") in 1880. But scientists were sceptical until Golgi intervened. It was Golgi who helped him prove that malarial parasite was a microscopic protozoan. From 1885, Golgi studied the malarial parasite and its transmission. He established two types of malaria, tertian and quartan fevers caused by "Plasmodium vivax" and "Plasmodium malariae" respectively. In 1886, he discovered that malarial fever (paroxysm) was produced by the asexual stage in the human blood (called erythocytic cycle, or Golgi cycle). In 1889-1890, Golgi and Ettore Marchiafava described the differences between benign tertian malaria and malignant tertian malaria (the latter caused by "P. falciparum"). By 1898, along with Giovanni Battista Grassi, Amico Bignami, Giuseppe Bastianelli, Angelo Celli and Marchiafava, he confirmed that malaria was transmitted by "Anopheline" mosquito.
The Microbiology Society (previously the Society for General Microbiology) is a learned society based in the United Kingdom with a worldwide membership based in universities, industry, hospitals, research institutes and schools. It is the largest learned microbiological society in Europe. Interests of its members include basic and applied aspects of viruses, prions, bacteria, rickettsiae, mycoplasma, fungi, algae and protozoa, and all other aspects of microbiology. Its headquarters in Charles Darwin House, London. The society's current president is Prof. Neil Gow. The Society is a member of the Science Council.
Moudgal's early researches at the University of Madras were on the biochemistry of thyroid hormones but he shifted his focus to pituitary gonadotropins during his days at Choh Hao Li's laboratory at the University of California, Berkeley when he established that the hormones generated immune response in living beings and the discovery was reported to be a significant one as the belief till then was the principal function of the hormones was reproduction. Later, at Rodney Porter's laboratory in London, he worked on the role of cellulose as a carrier for immobilization of antibodies. Back in India, he expanded the scope of his researches to cover wider aspects of reproductive biology for which he established a Primate Research Laboratory at IISc in 1965, which was the largest primate house in the country at that time. Working on the macaques in his primate house, he discovered that sialidase from the kidney of the primate acted as an inhibitor of follicle stimulating hormone (FSH), a hormone responsible for pubertal development. He conducted elaborate studies on the molecular mechanism of Luteinizing Hormone (LH), a hormone which has significant role in ovulation and testosterone production, and elucidated the "unfolding of LH binding to LH receptors in the target cell" which was detailed in one of his articles, "Effect of ICSH on Early Pregnancy in Hypophysectomized Pregnant Rats", published in Nature in 1969. He discovered that neutralizing LH resulted in neutralization of several reproductive functions such as ovulation, implantation, and gestational progress and the discovery opened a new methodology in immunocontraceptive technology. Later, he furthered his investigations on hormone actions by using antibodies as probes. His findings reportedly prompted R. O. Greep of Harvard University to invite him for collaborative research and Moudgal supervised the work of Greep's Group at his laboratory. At Harvard, he also collaborated with W. R. Moyle and established the presence of Luteinizing hormone/choriogonadotropin receptors on tumor cells in the testicles for the first time, which they revealed in an article, "Specific binding of luteinizing hormone to Leydig tumor cells", published in the Journal of Biological Chemistry in 1971. He used these tumor cells for further investigations on Hormone-Receptor interactions, Cyclic adenosine monophosphate (cyclic AMP) production and steroidogenesis and experimentally demonstrated the extent of coupling and response with regard to cyclic AMP production and steroid output.
Studies were completed consistently throughout Molaison's lifetime to discover more about amnesia. Researchers did a 14-year follow-up study on Molaison. They studied him for a period of two weeks to learn more about his amnesia. After 14 years, Molaison still could not recall things that had happened since his surgery. However, he could still remember things that had happened prior to the operation. Researchers also found that, when asked, Molaison could answer questions about national or international events, but he could not remember his own personal memories. After his death Molaison donated his brain to science, where they were able to discover the areas of the brain that had the lesions which caused his amnesia. This case study provided important insight to the areas of the brain that are affected in anterograde amnesia, as well as how amnesia works.
The genus "Neisseria" is named after the German bacteriologist Albert Neisser, who in 1879 discovered its first example, "Neisseria gonorrheae", the pathogen which causes the human disease gonorrhea. Neisser also codiscovered the pathogen that causes leprosy, "Mycobacterium leprae". These discoveries were made possible by the development of new staining techniques which he helped to develop.
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.
The Microwave Research Institute (MRI) was founded in 1945 by Ernst Weber at the Polytechnic Institute of Brooklyn (which later became the Polytechnic Institute of New York University). Research conducted at the institute included work in the areas of "electromagnetic theory, antennas and radiation, network theory and microwave networks, microwave components and devices." MRI was internationally regarded as one of the foremost centers of research on microwave field theory in the world. In 1985 it was renamed the Weber Research Institute in honor of its founder.Among its most prominent members were Nathan Marcuvitz, Leo B. Felsen, Dante C. Youla and Arthur A. Oliner, all fellows of IEEE and members of the National Academy of Engineering. The institute has attracted researchers from all over the world, including Alexander Graham Bell Medal winner Tsuneo Nakahara, who in 1961 was a visiting research associate of the institute, and who went on to be vice chairman of the Sumitomo Electric Company, and Dr. Oguchi, who became chief engineer of Nippon Telegraph and Telephone. Another faculty member closely associated with MRI was KunMo Chung, Director of the Plasma Physics Laboratory from 1967 to 1975, who served as Minister of Science and Technology of South Korea two times and who was associated with numerous international science and technology agencies.
The eye's fundus is the only part of the human body where the microcirculation can be observed directly. The diameter of the blood vessels around the optic disc is about 150 μm, and an ophthalmoscope allows observation of blood vessels with diameters as small as 10 μm.
Autophagy was first observed by Keith R. Porter and his student Thomas Ashford at the Rockefeller Institute. In January 1962 they reported an increased number of lysosomes in rat liver cells after the addition of glucagon, and that some displaced lysosomes towards the centre of the cell contained other cell organelles such as mitochondria. They called this autolysis after Christian de Duve and Alex B. Novikoff. However Porter and Ashford wrongly interpreted their data as lysosome formation (ignoring the pre-existing organelles). Lysosomes could not be cell organelles, but part of cytoplasm such as mitochondria, and that hydrolytic enzymes were produced by microbodies. In 1963 Hruban, Spargo and colleagues published a detailed ultrastructural description of "focal cytoplasmic degradation," which referenced a 1955 German study of injury-induced sequestration. Hruban, Spargo and colleagues recognized three continuous stages of maturation of the sequestered cytoplasm to lysosomes, and that the process was not limited to injury states that functioned under physiological conditions for "reutilization of cellular materials," and the "disposal of organelles" during differentiation. Inspired by this discovery, de Duve christened the phenomena "autophagy". Unlike Porter and Ashford, de Duve conceived the term as a part of lysosomal function while describing the role of glucagon as a major inducer of cell degradation in the liver. With his student Russell Deter, he established that lysosomes are responsible for glucagon-induced autophagy. This was the first time the fact that lysosomes are the sites of intracellular autophagy are established.
On July 24, 2009, the first publication of a successful breakthrough in Stem cell research was released, where Chinese researchers from the Shanghai Stem Cell Institute, led by Professor Fanyi Zeng, successfully reprogrammed adult stem cells to be able to differentiate into any body cell, as in the case with standard embryonic stem cells, the cells in question known as "induced pluripotent stem cells" (IPS cells). The IPS cells were obtained by genetically reprogramming the skin cells of mice to acts like embryonic stem cells, which then were able to differentiate into all forms of body tissue. The researchers have managed to use the IPS cells to create every type of cell in a mouse, creating entire mouse pups using the technique. This is the first time the technique has been used to make an entire mouse.
The name "autophagy" was coined by Belgian biochemist Christian de Duve in 1963 based on his discovery of the functions of lysosome. The identification of autophagy-related genes in yeast in the 1990s let researchers figure out the mechanisms of autophagy, which eventually led to the award of the 2016 Nobel Prize in Physiology or Medicine to Japanese researcher Yoshinori Ohsumi.
The scientific study of the nervous system increased significantly during the second half of the twentieth century, principally due to advances in molecular biology, electrophysiology, and computational neuroscience. This has allowed neuroscientists to study the nervous system in all its aspects: how it is structured, how it works, how it develops, how it malfunctions, and how it can be changed. For example, it has become possible to understand, in much detail, the complex processes occurring within a single neuron. Neurons are cells specialized for communication. They are able to communicate with neurons and other cell types through specialized junctions called synapses, at which electrical or electrochemical signals can be transmitted from one cell to another. Many neurons extrude a long thin filament of axoplasm called an axon, which may extend to distant parts of the body and are capable of rapidly carrying electrical signals, influencing the activity of other neurons, muscles, or glands at their termination points. A nervous system emerges from the assemblage of neurons that are connected to each other.
The first publicized discovery of a partial fossil mosasaur skull in 1764 by quarry workers in a subterranean gallery of a limestone quarry in Mount Saint Peter, near the Dutch city of Maastricht, preceded any major dinosaur fossil discoveries, but remained little known. However, a second find of a partial skull drew the Age of Enlightenment's attention to the existence of fossilized animals that were different from any known living creatures. When the specimen was discovered between 1770 and 1774, Johann Leonard Hoffmann, a surgeon and fossil collector, corresponded about it with the most influential scientists of his day, making the fossil famous. The original owner, though, was Godding, a canon of Maastricht cathedral.
Microbiology (from Greek , "mīkros", "small"; , "bios", "life"; and , "-logia") is the study of microorganisms, those being unicellular (single cell), multicellular (cell colony), or acellular (lacking cells). Microbiology encompasses numerous sub-disciplines including virology, parasitology, mycology and bacteriology.
Glutamate is also a neurotransmitter (see below), which makes it one of the most abundant molecules in the brain. Malignant brain tumors known as glioma or glioblastoma exploit this phenomenon by using glutamate as an energy source, especially when these tumors become more dependent on glutamate due to mutations in the gene "IDH1".
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 2012, Stevens’s team published evidence that microglia 'eat' synapses, especially those that are weak and unused. The findings pinned down a new role for microglia in wiring the brain, indicating that adult neural circuitry is determined not only by nerve cells but also by the brain’s immune cells; this helped to explain how the brain, which starts out with a surplus of neurons, trims some of the excess away. Neuron named the paper its most influential publication of 2012.
Glucocorticosteroids (GCS) are anti-inflammatory steroids that inhibit both central and peripheral cytokine synthesis and action. In a study conducted by Kalipada Pahan from the Department of Pediatrics at the Medical University of South Carolina, both lovastatin and sodium phenylacetate were found to inhibit TNF-α, IL-1β, and IL-6 in rat microglia. This shows that the mevalonate pathway plays a role in controlling the expression of cytokines in microglia and may be important in developing drugs to treat neurodegenerative diseases. Naltrexone may provide a solution to the inflammatory mediators produced by microglia. Although naltrexone's main action is to competitively bind to opioid receptors, new research shows that naltrexone, when given in low doses once per day (low-dose naltrexone), can inhibit cytokine synthesis by microglia cells. This mechanism is still being investigated, but there are already studies that indicate that it helps some patients suffering from fibromyalgia syndrome. Naltrexone shows more promise than GCSs because the GCSs inhibit immune system function more generally, increase allergic reactions and, as the name implies, increase blood glucose levels.
Many activated microglia are found to be associated with amyloid deposits in the brains of Alzheimer's patients. Microglia interact with β-amyloid plaques through cell surface receptors that are linked to tyrosine kinase based signaling cascades that induce inflammation. When microglia interact with the deposited fibrillar forms of β-amyloid it leads to the conversion of the microglia into an activated cell and results in the synthesis and secretion of cytokines and other proteins that are neurotoxic.
Microglial activation has been shown to be a reactive process in which microglia respond to signals given off by injured neurons. Because various characteristics of microgliosis occur in different time frames after the initial triggering insult, microgliosis must depend on mechanisms which fluctuate temporally based on injured neuronal signals. Studies have shown that in cases of reversible neuronal injury, such as axotomy, neuron signals cause microglia to produce trophic factors, which promote neuron survival. In cases of irreversible injury, however, microglia are induced to release neurotoxic factors that promote increased degeneration of the neuron and more rapid phagocytosis by the microglia. Such specificity of the process of microgliosis indicates that it primarily serves a beneficial purpose, selectively conserving some neural tissue while eliminating others, based on the specific initial CNS insult.