Dynein is a family of cytoskeletal motor proteins that move along microtubules in cells. They convert. Dynein transports various cellular cargos, provides forces and displacements important in mitosis, drives the beat of eukaryotic cilia and flagella. All of these functions rely on dynein's ability to move towards the minus-end of the microtubules, known as retrograde transport, they are called "minus-end directed motors". In contrast, kinesin motor proteins move toward the microtubules' plus end. Dyneins can be divided into two groups: cytoplasmic dyneins and axonemal dyneins, which are called ciliary or flagellar dyneins. Axonemal heavy chain: DNAH1, DNAH2, DNAH3, DNAH5, DNAH6, DNAH7, DNAH8, DNAH9, DNAH10, DNAH11, DNAH12, DNAH13, DNAH14, DNAH17 intermediate chain: DNAI1, DNAI2 light intermediate chain: DNALI1 light chain: DNAL1, DNAL4 cytoplasmic heavy chain: DYNC1H1, DYNC2H1 intermediate chain: DYNC1I1, DYNC1I2 light intermediate chain: DYNC1LI1, DYNC1LI2, DYNC2LI1 light chain: DYNLL1, DYNLL2, DYNLRB1, DYNLRB2, DYNLT1, DYNLT3 Axonemal dynein causes sliding of microtubules in the axonemes of cilia and flagella and is found only in cells that have those structures.
Cytoplasmic dynein, found in all animal cells and plant cells as well, performs functions necessary for cell survival such as organelle transport and centrosome assembly. Cytoplasmic dynein moves processively along the microtubule. Cytoplasmic dynein helps to position the Golgi other organelles in the cell, it helps transport cargo needed for cell function such as vesicles made by the endoplasmic reticulum and lysosomes. Dynein is involved in the movement of chromosomes and positioning the mitotic spindles for cell division. Dynein carries organelles and microtubule fragments along the axons of neurons toward the cell body in a process called retrograde axoplasmic transport. Cytoplasmic dynein positions the spindle at the site of cytokinesis by anchoring to the cell cortex and pulling on astral microtubules emanating from centrosome. Budding yeast have been a powerful model organism to study this process and has shown that dynein is targeted to plus ends of astral microtubules and delivered to the cell cortex via an offloading mechanism.
Dynein and Kinesin can both be exploited by viruses to mediate the viral replication process. Many viruses use the microtubule transport system to transport nucleic acid/protein cores to intracellular replication sites after invasion past the cell membrane. Not much is known about virus' motor-specific binding sites, but it is known that some viruses contain proline-rich sequences which, when removed, reduces dynactin binding, axon transport, neuroinvasion in vivo; this suggests. Each molecule of the dynein motor is a complex protein assembly composed of many smaller polypeptide subunits. Cytoplasmic and axonemal dynein contain some of the same components, but they contain some unique subunits. Cytoplasmic dynein, which has a molecular mass of about 1.5 megadaltons, is a dimer of dimers, containing twelve polypeptide subunits: two identical "heavy chains", 520 kDa in mass, which contain the ATPase activity and are thus responsible for generating movement along the microtubule. The force-generating ATPase activity of each dynein heavy chain is located in its large doughnut-shaped "head", related to other AAA proteins, while two projections from the head connect it to other cytoplasmic structures.
One projection, the coiled-coil stalk, binds to and "walks" along the surface of the microtubule via a repeated cycle of detachment and reattachment. The other projection, the extended tail, binds to the light intermediate and light chain subunits which attach dynein to its cargo; the alternating activity of the paired heavy chains in the complete cytoplasmic dynein motor enables a single dynein molecule to transport its cargo by "walking" a considerable distance along a microtubule without becoming detached. Yeast dynein can walk along microtubules without detaching, however in metazoans, cytoplasmic dynein must be activated by the binding of dynactin, another multisubunit protein, essential for mitosis, a cargo adaptor; the tri-complex, which includes dynein, dynactin and a cargo adaptor, is ultra-processive and can walk long distances without detaching in order to reach the cargo's intracellular destination. Cargo adaptors identified thus far include Hook3, FIP3 and Spindly; the light intermediate chain, a member of the Ras superfamily, mediates the attachment of several cargo adaptors to the dynein motor.
The other tail subunits may help facilitate this interaction as evidenced in a low resolution structure of dynein-dynactin-BicD2. One major form of motor regulation within cells for dynein is dynactin, it may be required for all cytoplasmic dynein functions. It is the best studied dynein partner. Dynactin is a protein that aids in intracellular transport throughout the cell by linking to cytoplasmic dynein. Dynactin can function as a scaffold for other proteins to bind to, it functions as a recruiting factor that localizes dynein to where it should be. There is some evidence suggesting that it may regulate kinesin-2; the dynactin complex is composed of more than 20 subunits, of which p150 is the
BBC News is an operational business division of the British Broadcasting Corporation responsible for the gathering and broadcasting of news and current affairs. The department is the world's largest broadcast news organisation and generates about 120 hours of radio and television output each day, as well as online news coverage; the service maintains 50 foreign news bureaus with more than 250 correspondents around the world. Fran Unsworth has been Director of News and Current Affairs since January 2018; the department's annual budget is in excess of £350 million. BBC News' domestic and online news divisions are housed within the largest live newsroom in Europe, in Broadcasting House in central London. Parliamentary coverage is broadcast from studios in Millbank in London. Through the BBC English Regions, the BBC has regional centres across England, as well as national news centres in Northern Ireland and Wales. All nations and English regions produce their own local news programmes and other current affairs and sport programmes.
The BBC is a quasi-autonomous corporation authorised by Royal Charter, making it operationally independent of the government, who have no power to appoint or dismiss its director-general, required to report impartially. As with all major media outlets it has been accused of political bias from across the political spectrum, both within the UK and abroad; the British Broadcasting Company broadcast its first radio bulletin from radio station.2LO In 14 November 1922. Wishing to avoid competition, newspaper publishers persuaded the government to ban the BBC from broadcasting news before 7:00 pm, to force it to use wire service copy instead of reporting on its own. On Easter weekend in 1930, this reliance on newspaper wire services left the radio news service with no information to report after saying There is no news today. Piano music was played instead; the BBC gained the right to edit the copy and, in 1934, created its own news operation. However, it could not broadcast news before 6 PM until World War II.
Gaumont British and Movietone cinema newsreels had been broadcast on the TV service since 1936, with the BBC producing its own equivalent Television Newsreel programme from January 1948. A weekly Children's Newsreel was inaugurated on 23 April 1950, to around 350,000 receivers; the network began simulcasting its radio news on television in 1946, with a still picture of Big Ben. Televised bulletins began on 5 July 1954, broadcast from leased studios within Alexandra Palace in London; the public's interest in television and live events was stimulated by Elizabeth II's coronation in 1953. It is estimated that up to 27 million people viewed the programme in the UK, overtaking radio's audience of 12 million for the first time; those live pictures were fed from 21 cameras in central London to Alexandra Palace for transmission, on to other UK transmitters opened in time for the event. That year, there were around two million TV Licences held in the UK, rising to over three million the following year, four and a half million by 1955.
Television news, although physically separate from its radio counterpart, was still under radio news' control – correspondents provided reports for both outlets–and that first bulletin, shown on 5 July 1954 on the BBC television service and presented by Richard Baker, involved his providing narration off-screen while stills were shown. This was followed by the customary Television Newsreel with a recorded commentary by John Snagge, it was revealed that this had been due to producers fearing a newsreader with visible facial movements would distract the viewer from the story. On-screen newsreaders were introduced a year in 1955 – Kenneth Kendall, Robert Dougall, Richard Baker–three weeks before ITN's launch on 21 September 1955. Mainstream television production had started to move out of Alexandra Palace in 1950 to larger premises – at Lime Grove Studios in Shepherd's Bush, west London – taking Current Affairs with it, it was from here that the first Panorama, a new documentary programme, was transmitted on 11 November 1953, with Richard Dimbleby becoming anchor in 1955.
On 18 February 1957, the topical early-evening programme Tonight, hosted by Cliff Michelmore and designed to fill the airtime provided by the abolition of the Toddlers' Truce, was broadcast from Marconi's Viking Studio in St Mary Abbott's Place, Kensington – with the programme moving into a Lime Grove studio in 1960, where it maintained its production office. On 28 October 1957, the Today programme, a morning radio programme, was launched in central London on the Home Service. In 1958, Hugh Carleton Greene became head of Current Affairs, he set up a BBC study group whose findings, published in 1959, were critical of what the television news operation had become under his predecessor, Tahu Hole. The report proposed that the head of television news should take control, that the television service should have a proper newsroom of its own, with an editor-of-the-day. On 1 January 1960, Greene became Director-General and brought about big changes at BBC Television and BBC Television News. BBC Television News had been created in 1955, in response to the founding of ITN.
The changes made by Greene were aimed at making BBC reporting more similar to ITN, rated by study groups held by Greene. A newsroom was created at Alexandra Palace, television reporters were recruited and given the opportunity to write and voice their own scripts–without the "impossible burden" of having to cover stories for radio too. In 1987 thirty years John B
William E. Moerner
William Esco Moerner is an American physical chemist and chemical physicist with current work in the biophysics and imaging of single molecules. He is credited with achieving the first optical detection and spectroscopy of a single molecule in condensed phases, along with his postdoc, Lothar Kador. Optical study of single molecules has subsequently become a used single-molecule experiment in chemistry and biology. In 2014, he was awarded the Nobel Prize in Chemistry. Moerner was born in Pleasanton, California, in 1953 June 24 the son of Bertha Frances and William Alfred Moerner, he became an Eagle Scout. He attended Washington University in St. Louis for undergraduate studies as an Alexander S. Langsdorf Engineering Fellow, obtained three degrees: a B. S. in physics with Final Honors, a B. S. in electrical engineering with Final Honors, an A. B. in mathematics summa cum laude in 1975. This was followed by graduate study supported by a National Science Foundation Graduate Fellowship, at Cornell University in the group of Albert J. Sievers III.
Here he received an M. S. degree and a Ph. D. degree in physics in 1978 and 1982, respectively. His doctoral thesis was on vibrational relaxation dynamics of an IR-laser-excited molecular impurity mode in alkali halide lattices. Throughout his school years, Moerner was a straight A student from 1963 to 1982, won both the Dean's Award for Unusually Exceptional Academic Achievement as well as the Ethan A. H. Shepley Award for Outstanding Achievement when he graduated from college. Moerner worked at the IBM Almaden Research Center in San Jose, California, as a Research Staff Member from 1981 to 1988, a Manager from 1988 to 1989, Project Leader from 1989 to 1995. After an appointment as Visiting Guest Professor of Physical Chemistry at ETH Zurich, he assumed the Distinguished Chair in Physical Chemistry in the Department of Chemistry and Biochemistry at the University of California, San Diego, from 1995 to 1998. In 1997 he was named the Robert Burns Woodward Visiting Professor at Harvard University.
His research group moved to Stanford University in 1998 where he became Professor of Chemistry, Harry S. Mosher Professor, Professor, by courtesy, of Applied Physics. Moerner was appointed Department Chair for Chemistry from 2011 to 2014, his current areas of research and interest include: single-molecule spectroscopy and super-resolution microscopy, physical chemistry, chemical physics, nanoparticle trapping, photorefractive polymers, spectral hole-burning. As of May 2014, Moerner was listed as a faculty advisor in 26 theses written by Stanford graduate students; as of May 16, 2014, there are 386 publications listed in Moerner's full CV. Recent editorial and advisory boards Moerner has served on include: Member of the Board of Scientific Counselors for the National Institute of Biomedical Imaging and Bioengineering. Moerner is the recipient of a number of honors, they include: National Winner of the Outstanding Young Professional Award for 1984, from the electrical engineering honorary society, Eta Kappa Nu, April 22, 1985.
Moerner holds more than a dozen patents. His honorary memberships include Senior Member, IEEE, June 17, 1988, Member, National Academy of Sciences, 2007, he is a Fellow of the Optical Society of America, May 28, 1992. Moerner was born on June 1953, at Parks Air Force Base in Pleasanton, California. From birth, his family called him by his initials W. E. as a way to distinguish him from his father and grandfather who are named William. He grew up in Texas, he participated in many activities during high school: Band and Debate, Math and Science Contest Team, Bi-Phy-Chem and Gavel, National Honor Society, Boy Scouts, Amateur Radio Club, Russian Club, Forum Social Club, Toastmasters, "On the Spot" Team and Editor of Each has Spoken. Moerner and his wife, have one son, Daniel. Chemistry Tree: William E. Moerner Details Faculty Page at Stanford's Chemistry Department Moerner Laboratory Homepage W. E. Moerner | Stanford University Profiles NIH Biosketch for W. E. Moerner Google Scholar Profile for W. E. Moerner Microsoft Academic Search pagefor W. E. Moerner List of Nobel laureates affiliated with Washington University in St. Louis Description of Moerner's work: Alumni Alumni Achievement Award from Washington University
Robert Eric Betzig is an American physicist based at the Janelia Farm Research Campus in Ashburn, Virginia. He has worked to develop the field of fluorescence microscopy and photoactivated localization microscopy, he was awarded the 2014 Nobel Prize in Chemistry for "the development of super-resolved fluorescence microscopy" along with Stefan Hell and fellow Cornell alumnus William E. Moerner. Betzig was born in Ann Arbor, Michigan in 1960, the son of Robert Betzig, an engineer, Helen Betzig. Aspiring to work in the aerospace industry, Betzig studied Physics at the California Institute of Technology and graduated with a BS degree in 1983, he went on to study at Cornell University where he was advised by Aaron Lewis and Michael Isaacson. There he obtained an MS degree and a PhD degree in Applied and Engineering physics in 1985 and 1988, respectively. For his PhD he focused on developing high resolution optical microscopes that could see past the theoretical limit of.2 micrometers. After receiving his doctorate, Betzig was hired by AT&T Bell Laboratories in the Semiconductor Physics Research Department in 1989.
That year Betzig's colleague, William E. Moerner, developed the first optical microscope that could see past the.2 micrometer limit, known as the Abbe limit, but it could only function at temperatures near absolute zero. Betzig was awarded the William L. McMillan Award in 1992. Inspired by Moerner's research, he became the first person to image individual fluorescent molecules at room temperature while determining their positions to more than.2 micrometers in 1993. For this he received the William O. Baker Award for Initiatives in Research, at the time, the National Academy of Sciences Award for Initiatives in Research. In 1994, Betzig became frustrated with the academic community and the uncertainty of the corporate structure of Bell Laboratories causing him to leave both, he spent some years as a house husband before reentering the workforce. At his father's wish, in 1996 he took up the position of vice president of research and development at Ann Arbor Machine Company owned by the Betzig family.
Here he developed Flexible Adaptive Servohydraulic Technology and after spending millions of dollars on development, sold a total of two devices which did not allow him to achieve commercial success. In 2002, Betzig returned to the field of microscopy by founding a firm known as New Millennium Research, in Okemos, Michigan. Inspired by the work of Mike Davidson and his fluorescent proteins, he developed photoactivated localization microscopy, a method of controlling fluorescent proteins using pulses of light to create images of a higher resolution than thought possible. In the living room of his old Bell Labs collaborator, Harald Hess, they developed the first optical microscope based on this technology, they built their first prototype in less than two months. In October of that year, Janelia hired him. In early 2006, he formally joined the Howard Hughes Medical Institute's Janelia Farm Research Campus as a group leader to work on developing super high-resolution fluorescence microscopy techniques.
He used this technique to study the division of cells in human embryos. In 2010, he was offered the Max Delbruck Prize, but he declined it allowing Xiaowei Zhuang to receive the award. In 2014, Betzig was jointly awarded the Nobel Prize in Chemistry along with Stefan Hell and William E. Moerner. In the summer of 2017, Betzig joined the faculty of UC Berkeley with a joint appointment at Lawrence Berkeley National Laboratory. Eric Betzig talk: Developing PALM Microscopy Eric Betzig, SPIE Photonics West plenary presentation: Single molecules and super-resolution optics Eric Betzig, Beyond the Nobel Prize -- New approaches to microscopy
A flagellum is a lash-like appendage that protrudes from the cell body of certain bacteria and eukaryotic cells termed as flagellates. A flagellate can have several flagella; the primary function of a flagellum is that of locomotion, but it often functions as a sensory organelle, being sensitive to chemicals and temperatures outside the cell. The similar structure in the archaea functions in the same way but is structurally different and has been termed the archaellum. Flagella are organelles defined by function rather than structure. Flagella vary greatly. Both prokaryotic and eukaryotic flagella can be used for swimming but they differ in protein composition and mechanism of propulsion; the word flagellum in Latin means whip. An example of a flagellated bacterium is the ulcer-causing Helicobacter pylori, which uses multiple flagella to propel itself through the mucus lining to reach the stomach epithelium. An example of a eukaryotic flagellate cell is the mammalian sperm cell, which uses its flagellum to propel itself through the female reproductive tract.
Eukaryotic flagella are structurally identical to eukaryotic cilia, although distinctions are sometimes made according to function or length. Fimbriae and pili are thin appendages, but have different functions and are smaller. Three types of flagella have so far been distinguished: bacterial and eukaryotic; the main differences among these three types are: Bacterial flagella are helical filaments, each with a rotary motor at its base which can turn clockwise or counterclockwise. They provide two of several kinds of bacterial motility. Archaeal flagella are superficially similar to bacterial flagella, but are different in many details and considered non-homologous. Eukaryotic flagella—those of animal and protist cells—are complex cellular projections that lash back and forth. Eukaryotic flagella are classed along with eukaryotic motile cilia as undulipodia to emphasize their distinctive wavy appendage role in cellular function or motility. Primary cilia are immotile, are not undulipodia; the bacterial flagellum is made up of the protein flagellin.
Its shape is a 20-nanometer-thick hollow tube. It has a sharp bend just outside the outer membrane. A shaft runs between the hook and the basal body, passing through protein rings in the cell's membrane that act as bearings. Gram-positive organisms have two of these basal body rings, one in the peptidoglycan layer and one in the plasma membrane. Gram-negative organisms have four such rings: the L ring associates with the lipopolysaccharides, the P ring associates with peptidoglycan layer, the M ring is embedded in the plasma membrane, the S ring is directly attached to the plasma membrane; the filament ends with a capping protein. The flagellar filament is the long, helical screw that propels the bacterium when rotated by the motor, through the hook. In most bacteria that have been studied, including the Gram-negative Escherichia coli, Salmonella typhimurium, Caulobacter crescentus, Vibrio alginolyticus, the filament is made up of 11 protofilaments parallel to the filament axis; each protofilament is a series of tandem protein chains.
However, Campylobacter jejuni has seven protofilaments. The basal body has several traits in common with some types of secretory pores, such as the hollow, rod-like "plug" in their centers extending out through the plasma membrane; the similarities between bacterial flagella and bacterial secretory system structures and proteins provide scientific evidence supporting the theory that bacterial flagella evolved from the type-three secretion system. The bacterial flagellum is driven by a rotary engine made up of protein, located at the flagellum's anchor point on the inner cell membrane; the engine is powered by proton motive force, i.e. by the flow of protons across the bacterial cell membrane due to a concentration gradient set up by the cell's metabolism. The rotor transports protons across the membrane, is turned in the process; the rotor alone can operate at 6,000 to 17,000 rpm, but with the flagellar filament attached only reaches 200 to 1000 rpm. The direction of rotation can be changed by the flagellar motor switch instantaneously, caused by a slight change in the position of a protein, FliG, in the rotor.
The flagellum is energy efficient and uses little energy. The exact mechanism for torque generation is still poorly understood; because the flagellar motor has no on-off switch, the protein epsE is used as a mechanical clutch to disengage the motor from the rotor, thus stopping the flagellum and allowing the bacterium to remain in one place. The cylindrical shape of flagella is suited to locomotion of microscopic organisms; the rotational speed of flagella varies in response to the intensity of the proton motive force, thereby permitting certain forms of speed control, permitting some types of bacteria to attain remarkable speeds in proportion to their size. At such a speed, a bacterium would take about 245 days to cover 1 km. In comparison to macroscopic life forms, it is fast indeed when expressed in terms of number of body lengths p
A molecular machine, nanite, or nanomachine, refers to any discrete number of molecular components that produce quasi-mechanical movements in response to specific stimuli. In biology, macromolecular machines perform tasks essential for life such as DNA replication and ATP synthesis; the expression is more applied to molecules that mimic functions that occur at the macroscopic level. The term is common in nanotechnology where a number of complex molecular machines have been proposed that are aimed at the goal of constructing a molecular assembler. For the last several decades and physicists alike have attempted, with varying degrees of success, to miniaturize machines found in the macroscopic world. Molecular machines research is at the forefront with the 2016 Nobel Prize in Chemistry being awarded to Jean-Pierre Sauvage, Sir J. Fraser Stoddart and Bernard L. Feringa for the design and synthesis of molecular machines. Molecular machines can be divided into two broad categories. In general, artificial molecular machines refer to molecules that are artificially designed and synthesized whereas biological molecular machines can be found in nature.
A wide variety of artificial molecular machines have been synthesized by chemists which are rather simple and small compared to biological molecular machines. The first AMM, a molecular shuttle, was synthesized by Sir J. Fraser Stoddart. A molecular shuttle is a rotaxane molecule where a ring is mechanically interlocked onto an axle with two bulky stoppers; the ring can move between two binding sites with various stimuli such as light, pH, ions. As the authors of this 1991 JACS paper noted: “Insofar as it becomes possible to control the movement of one molecular component with respect to the other in a rotaxane, the technology for building molecular machines will emerge.”, mechanically interlocked molecular architectures spearheaded AMM design and synthesis as they provide directed molecular motion. Today a wide variety of AMMs exists as listed below. Molecular motors are molecules that are capable of rotary motion around a double bond. Single bond rotary motors are fueled by chemical reactions whereas double bond rotary motors are fueled by light.
The rotation speed of the motor can be tuned by careful molecular design. Carbon nanotube nanomotors have been produced. A molecular propeller is a molecule that can propel fluids when rotated, due to its special shape, designed in analogy to macroscopic propellers, it has several molecular-scale blades attached at a certain pitch angle around the circumference of a nanoscale shaft. See molecular gyroscope. A molecular switch is a molecule; the molecules may be shifted between the states in response to changes in pH, temperature, an electric current, microenvironment, or the presence of a ligand. A molecular shuttle is a molecule capable of shuttling molecules or ions from one location to another. A common molecular shuttle consists of a rotaxane where the macrocycle can move between two sites or stations along the dumbbell backbone. Nanocars are single molecule vehicles that resemble macroscopic automobiles and are important for understanding how to control molecular diffusion on surfaces; the first nanocars were synthesized by James M. Tour in 2005.
They had 4 molecular wheels attached to the four corners. In 2011, Ben Feringa and co-workers synthesized the first motorized nanocar which had molecular motors attached to the chassis as rotating wheels; the authors were able to demonstrate directional motion of the nanocar on a copper surface by providing energy from a scanning tunneling microscope tip. In 2017, worlds first Nanocar race took place in France. A molecular balance is a molecule that can interconvert between two and more conformational or configurational states in response to the dynamic of multiple intra- and intermolecular driving forces, such as hydrogen bonding, solvophobic/hydrophobic effects, π interactions, steric and dispersion interactions. Molecular tweezers are host molecules capable of holding items between their two arms; the open cavity of the molecular tweezers binds items using non-covalent bonding including hydrogen bonding, metal coordination, hydrophobic forces, van der Waals forces, π interactions, or electrostatic effects.
Examples of molecular tweezers have been reported that are constructed from DNA and are considered DNA machines. A molecular sensor is a molecule. Molecular sensors combine molecular recognition with some form of reporter, so the presence of the item can be observed. A molecular logic gate is a molecule that performs a logical operation on one or more logic inputs and produces a single logic output. Unlike a molecular sensor, the molecular logic gate will only output when a particular combination of inputs are present. A molecular assembler is a molecular machine able to guide chemical reactions by positioning reactive molecules with precision. A molecular hinge is a molecule that can be selectively switched from one configuration to another in a reversible fashion; such configurations must have distinguishable geometries, for instance, Cis or Trans isomers of a V-shape molecule. Azo compounds perform Cis–trans isomerism upon receiving UV-Vis light; the most complex macromolecular machines are found within cells in the form of multi-protein complexes.
Some biological machines are motor proteins, such as myosin, responsible for muscle contraction, which moves cargo inside cells away from the nucleus along microtubules, and