Cryogenic electron microscopyCryogenic electron microscopy (cryo-EM) is a cryomicroscopy technique applied on samples cooled to cryogenic temperatures. For biological specimens, the structure is preserved by embedding in an environment of vitreous ice. An aqueous sample solution is applied to a grid-mesh and plunge-frozen in liquid ethane or a mixture of liquid ethane and propane. While development of the technique began in the 1970s, recent advances in detector technology and software algorithms have allowed for the determination of biomolecular structures at near-atomic resolution.
Transmission electron cryomicroscopyTransmission electron cryomicroscopy (CryoTEM), commonly known as cryo-EM, is a form of cryogenic electron microscopy, more specifically a type of transmission electron microscopy (TEM) where the sample is studied at cryogenic temperatures (generally liquid-nitrogen temperatures). Cryo-EM is gaining popularity in structural biology. The utility of transmission electron cryomicroscopy stems from the fact that it allows the observation of specimens that have not been stained or fixed in any way, showing them in their native environment.
AmyloidAmyloids are aggregates of proteins characterised by a fibrillar morphology of typically 7–13 nm in diameter, a 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 within and around cells.
Amyloid betaAmyloid beta (Aβ or Abeta) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid-beta precursor protein (APP), which is cleaved by beta secretase and gamma secretase to yield Aβ in a cholesterol-dependent process and substrate presentation. Aβ molecules can aggregate to form flexible soluble oligomers which may exist in several forms.
Transmission electron microscopyTransmission electron microscopy (TEM) is a microscopy technique in which a beam of electrons is transmitted through a specimen to form an image. The specimen is most often an ultrathin section less than 100 nm thick or a suspension on a grid. An image is formed from the interaction of the electrons with the sample as the beam is transmitted through the specimen. The image is then magnified and focused onto an imaging device, such as a fluorescent screen, a layer of photographic film, or a sensor such as a scintillator attached to a charge-coupled device.
PrionA prion ˈpriːɒn is a misfolded protein that can transmit its misfoldedness to normal variants of the same protein and trigger cellular death. Prions cause prion diseases known as transmissible spongiform encephalopathies (TSEs) that are transmissible, fatal neurodegenerative diseases in humans and animals. The proteins may misfold sporadically, due to genetic mutations, or by exposure to an already misfolded protein. The consequent abnormal three-dimensional structure confers on them the ability to cause misfolding of other proteins.
Scanning transmission electron microscopyA scanning transmission electron microscope (STEM) is a type of transmission electron microscope (TEM). Pronunciation is [stɛm] or [ɛsti:i:ɛm]. As with a conventional transmission electron microscope (CTEM), images are formed by electrons passing through a sufficiently thin specimen. However, unlike CTEM, in STEM the electron beam is focused to a fine spot (with the typical spot size 0.05 – 0.2 nm) which is then scanned over the sample in a raster illumination system constructed so that the sample is illuminated at each point with the beam parallel to the optical axis.
Electron microscopeAn electron microscope is a microscope that uses a beam of electrons as a source of illumination. They use electron optics that are analogous to the glass lenses of an optical light microscope. As the wavelength of an electron can be up to 100,000 times shorter than that of visible light, electron microscopes have a higher resolution of about 0.1 nm, which compares to about 200 nm for light microscopes.
Amyloid plaquesAmyloid 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.
Transmissible spongiform encephalopathyTransmissible spongiform encephalopathies (TSEs) also known as prion diseases, are a group of progressive, incurable, and fatal conditions that are associated with prions and affect the brain and nervous system of many animals, including humans, cattle, and sheep. According to the most widespread hypothesis, they are transmitted by prions, though some other data suggest an involvement of a Spiroplasma infection. Mental and physical abilities deteriorate and many tiny holes appear in the cortex causing it to appear like a sponge when brain tissue obtained at autopsy is examined under a microscope.