Joaquin Rafael Phoenix is an American actor and producer. He has received numerous awards and nominations, including an Academy Award, a Grammy Award, two Golden Globe Awards; as a child, Phoenix started acting in television with his brother sister Summer. His first major film role was in SpaceCamp. During this period, he was credited as a name he gave himself, he went back to his original name and received positive reviews for his supporting work in the comedy-drama film To Die For and the period film Quills. He received wider attention for his portrayal of Commodus in the historical drama film Gladiator, for which he was nominated for the Academy Award for Best Supporting Actor, he subsequently earned Best Actor nominations for portraying musician Johnny Cash in Walk the Line, an alcoholic war veteran in The Master, the title character in Joker, winning for the latter. His other films include the horror films Signs and The Village, the historical drama Hotel Rwanda, the romantic drama Her, the crime satire Inherent Vice, the psychological thriller You Were Never Really Here, winning the Cannes Film Festival Award for Best Actor for the latter.
Phoenix has ventured into directing music videos, as well as producing films and television shows. For recording the soundtrack to Walk the Line, he won the Grammy Award for Best Compilation Soundtrack for Visual Media, he is a social activist and has lent his support to several charities and humanitarian organizations. He is on the board of directors for The Lunchbox Fund, a non-profit organization which provides daily meals to school students in the South African town of Soweto, he is known for his animal rights advocacy. For his lifelong dedication to animal rights, he was named PETA's Person of the Year in 2019. Phoenix was born Joaquin Rafael Bottom in the Río Piedras district of San Juan on October 28, 1974, the son of American parents from the U. S. mainland. He is the third of five children, following River and Rain, preceding Liberty and Summer, all of whom are actors, he has a half-sister named Jodean from his father's previous relationship. He was born with a mark on his lip, his father, John Lee Bottom, is from California and is of English descent with some German and remote French ancestry.
His mother, was born in New York City to Ashkenazi Jewish parents and is of Hungarian and Russian descent. Arlyn moved to California, they married in 1969. They became disenchanted with the cult and decided to leave the group, returning to the U. S. in 1977 when Phoenix was three years old. They changed their last name to Phoenix, after the mythical bird that rises from its own ashes, symbolizing a new beginning. Phoenix began calling himself "Leaf" around this time, having been inspired by spending time outdoors raking leaves and desiring to have a nature-related name like his siblings; this became the name he used as a child actor, until he changed it back to Joaquin at age 15. In order to provide food and financial support for the family, the children performed at various talent contests and playing instruments. In Los Angeles, his mother started working as an executive secretary for NBC, his father worked as a landscape architect. Phoenix and his siblings were discovered by one of Hollywood's leading children's agents, Iris Burton, who got the five children acting work doing commercials and television show appearances.
At the age of eight, Joaquin made his acting debut alongside his brother River in the television series Seven Brides for Seven Brothers in the 1982 episode "Christmas Song". In his first major role, Phoenix co-starred opposite River in the ABC Afterschool Special entitled Backwards: The Riddle of Dyslexia. In 1984, Phoenix made guest appearances in the Murder, She Wrote episode "We're Off to Kill the Wizard" with his sister Summer, individual episodes of The Fall Guy and Hill Street Blues. After appearing in the CBS television film Kids Don't Tell, Phoenix made his theatrical film debut in SpaceCamp as Max, a 12-year-old who goes to Kennedy Space Center to learn about the NASA space program and undergoes amateur astronaut training, he guest starred in the anthology series Alfred Hitchcock Presents episode "A Very Happy Ending" in the same year, playing a child who blackmails a hitman into killing his father. Phoenix's first starring role was in Russkies, about a group of friends who unknowingly befriend a Russian soldier during the Cold War.
Phoenix appeared in Ron Howard's comedy-drama Parenthood, in which he played the withdrawn teenage nephew of Steve Martin's character. The film was well grossed $126 million worldwide. Phoenix was nominated for the Young Artist Award for Best Leading Young Actor in a Feature Film for his performance in the film. After establishing himself as a child actor, Joaquin decided to retire from acting for a while and traveled to Mexico and South America with his father. On October 31, 1993, three days after Joaquin's 19th birthday, his older brother River died of an overdose outside The Viper Room. Phoenix, who had accompanied his brother and older sister Rain to the club, called 911 to seek help for his dying brother. After River's death, the phone call was broadcast o
The 2012 Women's European Championship or "European Cup" was the 17th annual rugby tournament organised by FIRA for the continent's national teams and the ninth official continental championship. Only eight teams took part - the lowest entry since 1996 and the first time since 1996 that Scotland and Ireland did not take part; the leading four teams played in Group A in Rovereto, Italy between 13 and 19 May, the other four played at Enköping between 3 and 7 May. The latter tournament started Europe's Women's Rugby World Cup qualification process, with both finalists qualifying for the continent's qualification tournament in 2013. Most of the absences were due to Unions prioritising sevens rugby, in advance of the 2013 Sevens World Cup; the teams attending the Group A tournament were weakened by clashes with the London and Rome Sevens tournaments. England were least affected as their players only missed the first round of games, but several French players from the Six Nations did not play in this tournament, while most of the Spanish team from 2011 Women's European Trophy were selected for the Amsterdam Sevens in preference to Rovereto.
Semi finals Third-place Final Women's international rugby union FIRA website
Hereditary sensory and autonomic neuropathy type I or hereditary sensory neuropathy type I is a group of autosomal dominant inherited neurological diseases that affect the peripheral nervous system on the sensory and autonomic functions. The hallmark of the disease is the marked loss of pain and temperature sensation in the distal parts of the lower limbs; the autonomic disturbances, if present, manifest as sweating abnormalities. The beginning of the disease adulthood. Since affected individuals cannot feel pain, minor wounds or blisters in the painless area may not be recognized and can develop into extensive and deep foot ulcerations. Once infection occurs, the complications such as inflammation and progressive destruction of the underlying bones may follow and may require amputation of the surrounding area. HSAN I is the most common type among the five types of HSAN; as a heterogeneous group of diseases, HSAN I can be divided into five subtypes HSAN IA-E. Most of the genes associated with the diseases have been identified.
However, the molecular pathways leading to the manifestation of the diseases are not understood. Therefore, the potential targets for therapeutic interventions are not known. Moreover, gene-based therapies for patients with the diseases are not available to date, hence supportive care is the only treatment available for the patients. At the beginning, affected individuals notice the loss of pain and temperature sensation or all sensory modalities in their feet; as the disease progresses, the sensory abnormalities may extend up to the knees. However, they do not notice sensory loss for a long time. Many affected individuals only become aware of the disease when they notice painless injuries and burns or when they seek medical advice for healing wounds or foot ulcers. Foot ulcerations may appear badly fitting shoes. Minor wounds or blisters may lead to deep foot ulcerations. Once infection occurs, complications such as inflammation and destruction of the underlying bones may follow. Affected individuals who do not lose sensation may experience spontaneous pain.
In addition, many affected individuals exhibit, to a variable degree, symmetrical distal muscle weakness and wasting. HSAN I is characterized by marked sensory disturbances as the loss of pain and temperature sensation in the distal parts of the lower limbs; the loss of sensation can extend to the proximal parts of the lower limbs and the upper limbs as the disease progresses. Some affected individuals do not lose sensation, but instead experience severe shooting and lancinating pains in the limbs or in the trunk. Autonomic disturbances, if present, manifest as decreased sweating; the degree of motor disturbances is variable within families, ranging from absent to severe distal muscle weakness and wasting. The disease progresses but disables the affected individuals after a long duration; the onset of the disease varies between the 2nd and 5th decade of life, albeit congenital or childhood onset has been reported. With the progression of the disease, the affected individuals lose the ability to feel pain in their feet and legs.
Minor injuries in the painless area can result in slow-healing wounds which, if not recognized, can develop into chronic ulcerations. Once infection occurs, these ulcerations can result in severe complications that lead to foot deformity, such as inflammation of the underlying bones, spontaneous bone fractures, progressive degeneration of weight-bearing joints. Furthermore, foot deformity promotes skin changes such as hyperkeratosis at pressure points; these complications may necessitate amputation of the affected foot. Biopsies of affected sural nerve in patients with HSAN I showed evidence of neuronal degeneration. Only a few myelinated fibers were observed some of which showed a sign of primary demyelination. A reasonable number of unmyelinated axons remained, although the presence of stacks of flattened Schwann cell processes suggested unmyelinated axon loss. Electrophysiological testing provides additional evidence that neuronal degeneration underlies the disease. Sensory potentials are absent in the lower limbs but are recordable or normal in the upper limbs of the patients.
In addition, motor conduction is slow implying a demyelinating process. Advances in molecular genetics have enabled identification of most genes associated with HSAN I. However, the molecular mechanisms that underlie the disease are not understood and are under investigation. One of challenges in the investigation is to elucidate how faulty genes that are ubiquitously expressed and are involved in basic cellular functions, such as sphingolipid metabolism, maintenance of organellar integrity, membrane dynamics, transcription regulation, affect specific populations of neurons. HSAN IA is associated with heterozygous missense mutations in the SPTLC1 gene; the gene encodes SPTLC1 protein, which together with SPTLC2 protein, forms serine palmitoyltransferase in humans. SPT is a pyridoxal-5'-phosphate-dependent enzyme that catalyzes the first and rate-limiting step in the de novo biosynthesis of sphingolipids. Together with cholesterol, sphingolipids form the main component of lipid rafts, structures in the plasma membrane that facilitate efficient signal transduction.
Many intermediate sphingoid bases and their derivatives, as well as complex sphingolipids, are active as extracellular and intracellular regulators of growth, migration and cellular responses to stress. Mutations in the SPTLC1 gene were associated with increased activity of SPT. Subsequent s