Biochemistry
It is still not fully understood why neurons die in ALS, but this neurodegeneration is thought to involve many different cellular and molecular processes. The genes known to be involved in ALS can be grouped into three general categories based on their normal function: protein degradation, the cytoskeleton, and RNA processing. Mutant SOD1 protein forms intracellular aggregations that inhibit protein degradation. Cytoplasmic aggregations of wild-type (normal) SOD1 protein are common in sporadic ALS. It is thought that misfolded mutant SOD1 can cause misfolding and aggregation of wild-type SOD1 in neighboring neurons in a prion-like manner. Other protein degradation genes that can cause ALS when mutated include VCP, OPTN, TBK1, and SQSTM1. Three genes implicated in ALS that are important for maintaining the cytoskeleton and for axonal transport include DCTN1, PFN1, and TUBA4A.There are a number of ALS genes that encode for RNA-binding proteins. The first to be discovered was TDP-43 protein, a nuclear protein that aggregates in the cytoplasm of motor neurons in almost all cases of ALS; however, mutations in TARDBP, the gene that codes for TDP-43, are a rare cause of ALS. FUS codes for FUS, another RNA-binding protein with a similar function to TDP-43, which can cause ALS when mutated. It is thought that mutations in TARDBP and FUS increase the binding affinity of the low-complexity domain, causing their respective proteins to aggregate in the cytoplasm. Once these mutant RNA-binding proteins are misfolded and aggregated, they may be able to misfold normal protein both within and between cells in a prion-like manner.
In politics
Four Freedoms: four fundamental freedoms that Franklin D. Roosevelt declared ought to be enjoyed by everyone in the world: Freedom of Speech, Freedom of Religion, Freedom from Want, Freedom from Fear. Gang of Four: Popular name for four Chinese Communist Party leaders who rose to prominence during Chinas Cultural Revolution, but were ousted in 1976 following the death of Chairman Mao Zedong. Among the four was Maos widow, Jiang Qing. Since then, many other political factions headed by four people have been called "Gangs of Four". In computing
Four bits (half a byte) are sometimes called a nibble. In science
A tetramer is an oligomer formed out of four sub-units. In astronomy
Four terrestrial (or rocky) planets in the Solar System: Mercury, Venus, Earth, and Mars. Four giant gas/ice planets in the Solar System: Jupiter, Saturn, Uranus, and Neptune. Four of Jupiters moons (the Galilean moons) are readily visible from Earth with a hobby telescope. Messier object M4, a magnitude 7.5 globular cluster in the constellation Scorpius. The Roman numeral IV stands for subgiant in the Yerkes spectral classification scheme. In biology
Four is the number of nucleobase types in DNA and RNA – adenine, guanine, cytosine, thymine (uracil in RNA). Many chordates have four feet, legs or leglike appendages (tetrapods). The mammalian heart consists of four chambers. Many mammals (Carnivora, Ungulata) use four fingers for movement. All insects with wings except flies and some others have four wings.