Measles morbillivirus Measles virus, is a single-stranded, negative-sense, non-segmented RNA virus of the genus Morbillivirus within the family Paramyxoviridae. It is the cause of measles. Humans are the natural hosts of the virus; the virus causes an infection of the respiratory system. Symptoms include fever, runny nose, red eyes and a generalized, erythematous rash; the virus is contagious and is spread by coughing and sneezing via close personal contact or direct contact with secretions. The measles virus has two envelope glycoproteins on the viral surface — hemagglutinin and membrane fusion protein; these proteins are responsible for host cell invasion. Three receptors for the H protein have been identified to date: complement regulatory molecule CD46, the signaling lymphocyte activation molecule and the cell adhesion molecule Nectin-4; the negative sense strand of ssRNA is used to create a positive copy this used to create a new negative copy, so on, to create many copies of the ssRNA. The ssRNA is mass translated by host ribosomes, producing necessary viral proteins.
The viruses are assembled, the cell will lyse, restarting the cycle. The measles virus evolved from the widespread rinderpest virus, which infects cattle. Sequence analysis has suggested that the two viruses most diverged in the 11th and 12th centuries, though the periods as early as the 5th century fall within the 95% confidence interval of these calculations. Other analysis has suggested that the divergence may be older because of the technique's tendency to underestimate ages when strong purifying selection is in action. There is some linguistic evidence for an earlier origin within the seventh century; the current epidemic strain evolved at the beginning of the 20th century—most between 1908 and 1943. The WHO recognises 8 clades of measles. Subtypes are designed with numerals -- D2 etc.. 23 subtypes are recognised. The 450 nucleotides that code for the C‐terminal 150 amino acids of N are the minimum amount of sequence data required for genotyping a measles virus isolate; the genotyping scheme was introduced in 1998 and extended in 2002 and 2003.
Despite the variety of measles genotypes, there is only one measles serotype. Antibodies to measles bind to the haemagluttinin protein; the major genotypes differ between countries and status of measles circulation within that country or region. Endemic transmission of measles virus was interrupted in the United States and Australia by 2000 and the Americas by 2002. "Measles virus". International Committee on Taxonomy of Viruses
In biology, a gene is a sequence of nucleotides in DNA or RNA that codes for a molecule that has a function. During gene expression, the DNA is first copied into RNA; the RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic trait; these genes make up different DNA sequences called genotypes. Genotypes along with developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes as well as gene–environment interactions; some genetic traits are visible, such as eye color or number of limbs, some are not, such as blood type, risk for specific diseases, or the thousands of basic biochemical processes that constitute life. Genes can acquire mutations in their sequence, leading to different variants, known as alleles, in the population; these alleles encode different versions of a protein, which cause different phenotypical traits.
Usage of the term "having a gene" refers to containing a different allele of the same, shared gene. Genes evolve due to natural selection / survival of the fittest and genetic drift of the alleles; the concept of a gene continues to be refined. For example, regulatory regions of a gene can be far removed from its coding regions, coding regions can be split into several exons; some viruses store their genome in RNA instead of DNA and some gene products are functional non-coding RNAs. Therefore, a broad, modern working definition of a gene is any discrete locus of heritable, genomic sequence which affect an organism's traits by being expressed as a functional product or by regulation of gene expression; the term gene was introduced by Danish botanist, plant physiologist and geneticist Wilhelm Johannsen in 1909. It is inspired by the ancient Greek: γόνος, that means offspring and procreation; the existence of discrete inheritable units was first suggested by Gregor Mendel. From 1857 to 1864, in Brno, he studied inheritance patterns in 8000 common edible pea plants, tracking distinct traits from parent to offspring.
He described these mathematically as 2n combinations where n is the number of differing characteristics in the original peas. Although he did not use the term gene, he explained his results in terms of discrete inherited units that give rise to observable physical characteristics; this description prefigured Wilhelm Johannsen's distinction between phenotype. Mendel was the first to demonstrate independent assortment, the distinction between dominant and recessive traits, the distinction between a heterozygote and homozygote, the phenomenon of discontinuous inheritance. Prior to Mendel's work, the dominant theory of heredity was one of blending inheritance, which suggested that each parent contributed fluids to the fertilisation process and that the traits of the parents blended and mixed to produce the offspring. Charles Darwin developed a theory of inheritance he termed pangenesis, from Greek pan and genesis / genos. Darwin used the term gemmule to describe hypothetical particles. Mendel's work went unnoticed after its first publication in 1866, but was rediscovered in the late 19th century by Hugo de Vries, Carl Correns, Erich von Tschermak, who reached similar conclusions in their own research.
In 1889, Hugo de Vries published his book Intracellular Pangenesis, in which he postulated that different characters have individual hereditary carriers and that inheritance of specific traits in organisms comes in particles. De Vries called these units "pangenes", after Darwin's 1868 pangenesis theory. Sixteen years in 1905, Wilhelm Johannsen introduced the term'gene' and William Bateson that of'genetics' while Eduard Strasburger, amongst others, still used the term'pangene' for the fundamental physical and functional unit of heredity. Advances in understanding genes and inheritance continued throughout the 20th century. Deoxyribonucleic acid was shown to be the molecular repository of genetic information by experiments in the 1940s to 1950s; the structure of DNA was studied by Rosalind Franklin and Maurice Wilkins using X-ray crystallography, which led James D. Watson and Francis Crick to publish a model of the double-stranded DNA molecule whose paired nucleotide bases indicated a compelling hypothesis for the mechanism of genetic replication.
In the early 1950s the prevailing view was that the genes in a chromosome acted like discrete entities, indivisible by recombination and arranged like beads on a string. The experiments of Benzer using mutants defective in the rII region of bacteriophage T4 showed that individual genes have a simple linear structure and are to be equivalent to a linear section of DNA. Collectively, this body of research established the central dogma of molecular biology, which states that proteins are translated from RNA, transcribed from DNA; this dogma has since been shown to have exceptions, such as reverse transcription in retroviruses. The modern study of genetics at the level of DNA is known as molecular genetics. In 1972, Walter Fiers and his team were the first to determine the sequence of a gene: that of Bacteriophage MS2 coat protein; the subsequent development of chain-termination DNA sequencing in 1977 by Frederick Sanger improved the efficiency of sequencing and turned it into a routine laboratory tool.
An automated version of the Sanger method was used in early phases of the
National Institute of Neurological Disorders and Stroke
The National Institute of Neurological Disorders and Stroke is a part of the U. S. National Institutes of Health, it conducts and funds research on brain and nervous system disorders and has a budget of just over US$1.5 billion. The mission of NINDS is "to reduce the burden of neurological disease—a burden borne by every age group, every segment of society, people all over the world". NINDS has established two major branches for research: an extramural branch that funds studies outside the NIH, an intramural branch that funds research inside the NIH. Most of NINDS' budget goes to fund extramural research. NINDS' basic science research focuses on studies of the fundamental biology of the brain and nervous system, neurodegeneration and memory, motor control, brain repair, synapses. NINDS funds clinical research related to diseases and disorders of the brain and nervous system, e.g. AIDS, Alzheimer disease, muscular dystrophy, multiple sclerosis, Parkinson disease, spinal cord injury and traumatic brain injury.
Established in 1950 by the U. S. Congress as the National Institute of Neurological Diseases and Blindness to help handle the casualties of World War II, NINDS grew along with the NIH. During the 1950s and 1960s, NINDS and the NIH had strong Congressional support and received significant appropriations. However, this funding declined in 1968; the NINDS was created in 1950 to study and treat the neurological and psychiatric casualties of World War II. Many service people had returned with serious brain injuries, nerve damage, psychic trauma. According to one estimate, "neurologically disabled veterans in the postwar years accounted for about 25 percent of the patients in general hospitals and 10 percent of those in psychiatric hospitals". In addition, 1.7 million American men had been rejected for military service due to a neuropsychiatric condition or learning disorder. NINDS was created as part of an effort to "revive the extinct neurological field". At the time and its focus on "emotional tensions due to interpersonal and cultural maladjustments" held sway in US medicine, while neurology, with its focus on the inner workings of the brain, had fallen out of favor.
During WWII, all of the administrative positions of the American Board of Psychiatry and Neurology held by the US armed services were filled by psychiatrists. After the war, a survey by the Veteran's Administration of the members of the American Board of Psychiatry and Neurology found that 48 were neurologists and 456 were psychiatrists. In 1948, Abe B. Baker, chair of neurology and psychiatry at the University of Minnesota, formed the American Academy of Neurology to give young neurologists a national organization to join. However, sustained research in neurology was not possible without a national institute. In the late 1940s and early 1950s, vocal American Neurological Association members testified before Congress, arguing that there needed to be such an institute, they articulated the arguments, made on a smaller scale by citizens' groups for diseases such as multiple sclerosis, cerebral palsy, muscular dystrophy and blindness. Members of the research grants committee of the National Institute of Mental Health, founded in 1949, contend that they helped provide an impetus for the new institute, as when reviewing grant applications they saw a significant number of neurological projects and proposed a separate institute for them.
The National Institute of Neurological Disorders and Blindness, the original name for the NINDS, was established on November 22, 1950, three months after President Harry Truman signed the Omnibus Medical Research Act on August 15, 1950. The legislation had been passed with the efforts of Senator Claude Pepper, responsible for helping the majority of the NIH institutes get their start, wealthy New York entrepreneur Mary Lasker, Fight for Sight founder Mildred Weisenfeld, who had retinitis pigmentosa. NINDB was not conceived of coherently at the beginning. For example, blindness was added because some concerned citizens raised the issue with Lasker who, in turn asked Congressman Andrew Biemiller to do so in Congress, he added it to the bill, being sympathetic with the cause since his mother was blind. NINDB was "responsible for conducting and supporting research and training in the 200 neurological and sensory disorders that affected 20 million individuals in the United States and were'the first cause of permanent crippling and the third cause of death.'"
Because the etiology of the most common neurological diseases was poorly understood, NINDB undertook both clinical and basic research on the disorders themselves and on treatments. In the beginning, the NINDB had an Advisory Council made of six medical professional and lay people, all appointed by the U. S. Surgeon General, they granted its funds. The NINDB's first annual budget was US$1.23 million. This came from the existing NIH budget, as Congress had not appropriated any new funds for the institute when it was created. Although the NINDB's budget was increased to $1.99 million in 1952, there was still no money for new research programs. Moreover, the institute had a lab; as Ingrid Farreras writes in her history, "The research conducted by the institute was still supported by the NIMH and the institute's survival was unclear."The NINDB's first director, Pearce Bailey, was appointed on October 3, 1951, came with experience from the Neuropsyc
Hepatitis B virus
Hepatitis B virus, abbreviated HBV, is a double-stranded DNA virus, a species of the genus Orthohepadnavirus and a member of the Hepadnaviridae family of viruses. This virus causes the disease hepatitis B. In addition to causing hepatitis, infection with HBV can lead to cirrhosis and hepatocellular carcinoma, it has been suggested that it may increase the risk of pancreatic cancer. Viral infection by Hepatitis B virus causes many hepatocyte changes due to the direct action of a protein encoded by the virus, HBx, to indirect changes due to a large increase in intracellular reactive oxygen species after infection. HBx appears to dysregulate a number of cellular pathways. HBx causes dysregulation in part by binding to genomic DNA, changing expression patterns of miRNAs, affecting histone methyltransferases, binding to SIRT1 protein to activate transcription, cooperating with histone methylases and demethylases to change cell expression patterns. HBx is responsible for the approximate 10,000-fold increase in intracellular ROS upon chronic HBV infection.
Increased ROS can be caused, in part, by localization of HBx to the mitochondria where HBx decreases the mitochondrial membrane potential. In addition, another HBV protein, HBsAg increases ROS through interactions with the endoplasmic reticulum; the increase in reactive oxygen species after HBV infection causes inflammation, which leads to a further increase in ROS. ROS cause more than 20 types of DNA damage. Oxidative DNA damage is mutagenic. In addition, repair of the DNA damage can cause epigenetic alterations at the site of the damage during repair of the DNA. Epigenetic alterations and mutations may cause defects in the cellular machinery that contribute to liver disease. By the time accumulating epigenetic and mutational changes cause progression to cancer, epigenetic alterations appear to have a larger role in this carcinogenesis than mutations. Only one or two genes, TP53 and ARID1A, are mutated in more than 20% of liver cancers while 41 genes each have hypermethylated promoters in more than 20% of liver cancers, with seven of these genes being hypermethylated in more than 75% of liver cancers.
In addition to alterations at the sites of DNA repair, epigenetic alterations are caused by HBx recruiting the DNA methyltransferase enzymes, DNMT1 and/or DNMT3A, to specific gene loci to alter their methylation levels and gene expression. HBx alters histone acetylation that can affect gene expression. Several thousand protein-coding genes appear to have HBx-binding sites. In addition to protein coding genes, about 15 microRNAs and 16 Long non-coding RNAs are affected by the binding of HBx to their promoters; each altered microRNA can affect the expression of several hundred messenger RNAs. Hepatitis B virus is classified as the type species of the Orthohepadnavirus, which contains eight other species; the genus is classified as part of the Hepadnaviridae family, which contains one other genus, Avihepadnavirus. This family of viruses have not been assigned to a viral order. Viruses similar to hepatitis B have been found in all apes, in Old World monkeys, in a New World woolly monkeys suggesting an ancient origin for this virus in primates.
The virus is divided into four major serotypes based on antigenic epitopes present on its envelope proteins. These serotypes are based on two mutually exclusive determinant pairs; the viral strains have been divided into ten genotypes and forty subgenotypes according to overall nucleotide sequence variation of the genome. The genotypes have a distinct geographical distribution and are used in tracing the evolution and transmission of the virus. Differences between genotypes affect the disease severity and likelihood of complications, response to treatment and vaccination; the serotypes and genotypes do not correspond. Genotype D has 10 subgenotypes. A number of as yet unclassified Hepatitis B like species have been isolated from bats. Hepatitis B virus is a member of the Hepadnavirus family; the virus particle, called Dane particle, consists of an outer lipid envelope and an icosahedral nucleocapsid core composed of protein. The nucleocapsid encloses the viral DNA and a DNA polymerase that has reverse transcriptase activity similar to retroviruses.
The outer envelope contains embedded proteins which are involved in viral binding of, entry into, susceptible cells. The virus is one of the smallest enveloped animal viruses with a virion diameter of 42 nm, but pleomorphic forms exist, including filamentous and spherical bodies lacking a core; these particles are not infectious and are composed of the lipid and protein that forms part of the surface of the virion, called the surface antigen, is produced in excess during the life cycle of the virus. It consists of: HBsAg HBcAg Hepatitis B virus DNA polymerase HBx; the function of this protein is not yet well known, but evidence suggests it plays a part in the activation of the viral transcription process. Hepatitis D virus requires HBV envelope particles to become virulent; the early evolution of the Hepatitis B, like that of all viruses, is difficult to establish. The divergence of orthohepadnavirus and avihepadnavirus occurred ~125,000 years ago. Both the Avihepadnavirus and Orthohepadna viruses began to diversify about 25,000 years ago.
The branching at this time lead to the emergence of the Orthohepadna genotypes A–H. Human strains have a most recent common ancestor dating back to 7,000 to 10,000 years ago; the Av
Merck Manual of Diagnosis and Therapy
The Merck Manual of Diagnosis and Therapy, referred to as The Merck Manual, is the world's best-selling medical textbook, the oldest continuously published English language medical textbook. First published in 1899, the current print edition of the book, the 20th Edition, was published in 2018. In 2014, Merck decided to move The Merck Manual to digital-only, online publication, available in both Professional and Consumer versions; the Merck Manual of Diagnosis and Therapy is one of several medical textbooks, collectively known as The Merck Manuals, which are published by Merck Publishing, a subsidiary of the pharmaceutical company Merck Co. Inc. in the United States and Canada, MSD in other countries in the world. Merck formerly published The Merck Index, An Encyclopedia of Chemicals and Biologicals; the first edition of The Merck Manual was published in 1899 by Merck & Co. Inc. for physicians and pharmacists and was titled Merck’s Manual of the Materia Medica. The 192 page book which sold for US $1.00, was divided into three sections, Part I was an alphabetical listing of all known compounds thought to be of therapeutic value with uses and doses.
Many of the terms used are now considered archaic, such as abasia, astasia and rubefacients - sternutatories, many of the agents listed are now not considered to be standard therapeutic agents but were considered useful at the time, including poisonous compounds such as mercury, lead and arsenic. There were 108 remedies listed for indigestion, including alcohol, cocaine, gold chloride, morphine, nux vomica, silver nitrate, “Turkish baths ”. Bismuth, magnesium salts were on the list, which are ingredients found in many modern gastrointestinal treatments available today. Arsenic was recommended for over 100 illnesses including anemia, hydrophobia and impotence; the formulas include “aletris cordial”, a “uterine tonic and restorative”, which contained “aletris farinosa or True Unicorn combined with aromatics”. The manufacturer, Rio Chemicals of St. Louis was clear to differentiate the inclusion of true unicorn rather than false unicorn in its preparation; the earliest versions did contain drugs that are still in use today for the same purposes, for example digitalis for heart failure.
The second edition of The Merck Manual was published in 1901, was expanded to 282 pages and included new sections on poisons and antidotes and conversion charts, a detailed explanation of the metric system. The 5th edition, published in 1923 was delayed due to paper shortages caused by World War I, the release of the 6th edition was delayed until 1934 due to the Stock Market Crash; the editor of that edition, Dr. M. R. Dinkelspiel had overseen the growth and reorganization of the Manual to discuss specific diseases and treatment options, external specialists reviewed each section; the 8th edition of the Manual was delayed by World War II until 1950. The 13th edition, released in 1977 was the first time the textbook was produced using magnetic tape and IBM punch cards, the previous version having been typed on a manual typewriter; the Centennial Edition published in 1999 included a separate facsimile version of the 1899 1st edition. It is reported that both Admiral Richard E. Byrd took the book with him on his expedition to the South Pole in 1929 and Albert Schweitzer had a copy of The Merck Manual with him at his hospital mission in Africa in 1913.
The recommended doses given in Part 1 of 1901 edition of The Manual were for adults when given by mouth. It included the following dose adjustment recommendations: 1899 1901 1905 1911 1923 1934 1940 1950 1956 1961 1966 1972 1977 1982 1984 1992 1999 2006 2011 2018 The Merck Manual is organized, like many internal medicine textbooks, into organ systems which discuss each major diseases of that system, covering diagnosis and treatment, it provides a comprehensive yet concise compendium of medical knowledge into about 3500 pages, by emphasizing practical information of use to a practicing physician. In addition to 24 sections covering medical topics, it includes a pharmacology section listing drugs by generic and brand name, a list of drug interactions and a pill identifier, a News and Commentary section, videos on procedures and examination techniques and case histories, clinical calculators, conversion tables and other resources; the text is characterized by the combination of conciseness and being up-to-date.
It is updated continuously by an independent editorial board and over 300 peer reviewers that contribute to the textbook, which goes through an average of 10 revisions by both internal and external reviewers before publication. The internal editorial staff consists of 4 physician reviews, one executive editor and 4 non-medical lay editors; the latest version has been translated
A DNA virus is a virus that has DNA as its genetic material and replicates using a DNA-dependent DNA polymerase. The nucleic acid is double-stranded DNA but may be single-stranded DNA. DNA viruses belong to either Group Group II of the Baltimore classification system for viruses. Single-stranded DNA is expanded to double-stranded in infected cells. Although Group VII viruses such as hepatitis B contain a DNA genome, they are not considered DNA viruses according to the Baltimore classification, but rather reverse transcribing viruses because they replicate through an RNA intermediate. Notable diseases like smallpox and the chickenpox are caused by such DNA viruses. Genome organization within this group varies considerably; some have circular genomes. Some families have circularly permuted linear genomes. Others have linear genomes with covalently closed ends. A virus infecting archaea was first described in 1974. Several others have been described since: most have head-tail morphologies and linear double-stranded DNA genomes.
Other morphologies have been described: spindle shaped, rod shaped, filamentous and spherical. Additional morphological types may exist. Orders within this group are defined on the basis of morphology rather than DNA sequence similarity, it is thought that morphology is more conserved in this group than sequence similarity or gene order, variable. Three orders and 31 families are recognised. A fourth order — Megavirales — for the nucleocytoplasmic large DNA viruses has been proposed; this proposal has yet to be ratified by the ICTV. Four genera are recognised. Fifteen families are enveloped; these include all three families in the order Herpesvirales and the following families: Ascoviridae, Asfarviridae, Fuselloviridae, Guttaviridae, Iridoviridae, Lipothrixviridae and Poxviridae. Bacteriophages belonging to the families Tectiviridae and Corticoviridae have a lipid bilayer membrane inside the icosahedral protein capsid and the membrane surrounds the genome; the crenarchaeal virus Sulfolobus turreted.
The genomes in this group vary from ~10 kilobases to over 2.5 megabases in length. The largest bacteriophage known is Klebsiella Phage vB_KleM-RaK2 which has a genome of 346 kilobases; the virophages are a group of viruses. A virus with a novel method of genome packing infecting species of the genus Sulfolobus has been described; as this virus does not resemble any known virus it has been classified into a new family, the Portogloboviridae. Another Sulfolobus infecting virus - Sulfolobus ellipsoid virus 1 - has been described; this enveloped virus may be classified into a new taxon. Species of the order Caudovirales and of the families Corticoviridae and Tectiviridae infect bacteria. Species of the order Ligamenvirales and the families Ampullaviridae, Clavaviridae, Globuloviridae, Guttaviridae and Turriviridae infect hyperthermophilic archaea species of the Crenarchaeota. Species of the order Herpesvirales and of the families Adenoviridae, Iridoviridae, Papillomaviridae and Poxviridae infect vertebrates.
Species of the families Ascovirus, Hytrosaviridae and Polydnaviruses and of the genus Nudivirus infect insects. Species of the family Mimiviridae and the species Marseillevirus, Mavirus virophage and Sputnik virophage infect protozoa. Species of the family Nimaviridae infect crustaceans. Species of the family Phycodnaviridae and the species Organic Lake virophage infect algae; these are the only known dsDNA viruses. Species of the family Plasmaviridae infect species of the class Mollicutes. Species of the family Pandoraviridae infect amoebae. Species of the genus Dinodnavirus infect dinoflagellates; these are the only known viruses. Species of the genus Rhizidiovirus infect stramenopiles; these are the only known dsDNA viruses. Species of the genus Salterprovirus and Sphaerolipoviridae infect species of the Euryarchaeota. Order Caudovirales Family Myoviridae—includes Enterobacteria phage T4 Family Podoviridae—includes Enterobacteria phage T7 Family Siphoviridae—includes Enterobacteria phage λ Order Herpesvirales Family Alloherpesviridae Family Herpesviridae—includes human herpesviruses, Varicella Zoster virus Family Malacoherpesviridae Order Ligamenvirales Family Lipothrixviridae Family Rudiviridae Unassigned families Family Adenoviridae—includes viruses which cause human adenovirus infection Family Ampullaviridae Family Ascoviridae Family Asfarviridae—includes African swine fever virus Family Baculoviridae Family Bicaudaviridae Family Clavaviridae Family Corticoviridae Family Fuselloviridae Family Globuloviridae Family Guttaviridae Family Hytrosaviridae Family Iridoviridae Family Lavidaviridae Family Marseilleviridae Family Mimiviridae Family Nudiviridae Family Nimaviridae Family Pandoraviridae Family Papillomaviridae Family Phycodnaviridae Family Plasmaviridae Family Polydnaviruses Family Polyomaviridae—includes Simian virus 40, JC virus, BK virus Family Poxviridae—includes Cowpox virus, smallpox Family Sphaerolipoviridae Family Tectiviridae Family Tristromaviridae Family Turriviridae Unassigned genera Dinodnavirus Salterprovirus Rhizidiovirus Unassigned species Abalone shriveling syndrome-associated virus Bandicoot papillomatosis carcinomatosis vi
The Washington Post
The Washington Post is a major American daily newspaper published in Washington, D. C. with a particular emphasis on national politics and the federal government. It has the largest circulation in the Washington metropolitan area, its slogan "Democracy Dies in Darkness" began appearing on its masthead in 2017. Daily broadsheet editions are printed for the District of Columbia and Virginia; the newspaper has won 47 Pulitzer Prizes. This includes six separate Pulitzers awarded in 2008, second only to The New York Times' seven awards in 2002 for the highest number awarded to a single newspaper in one year. Post journalists have received 18 Nieman Fellowships and 368 White House News Photographers Association awards. In the early 1970s, in the best-known episode in the newspaper's history, reporters Bob Woodward and Carl Bernstein led the American press' investigation into what became known as the Watergate scandal, their reporting in The Washington Post contributed to the resignation of President Richard Nixon.
In years since, the Post's investigations have led to increased review of the Walter Reed Army Medical Center. In October 2013, the paper's longtime controlling family, the Graham family, sold the newspaper to Nash Holdings, a holding company established by Jeff Bezos, for $250 million in cash; the Washington Post is regarded as one of the leading daily American newspapers, along with The New York Times, the Los Angeles Times, The Wall Street Journal. The Post has distinguished itself through its political reporting on the workings of the White House and other aspects of the U. S. government. Unlike The New York Times and The Wall Street Journal, The Washington Post does not print an edition for distribution away from the East Coast. In 2009, the newspaper ceased publication of its National Weekly Edition, which combined stories from the week's print editions, due to shrinking circulation; the majority of its newsprint readership is in the District of Columbia and its suburbs in Maryland and Northern Virginia.
The newspaper is one of a few U. S. newspapers with foreign bureaus, located in Beirut, Beijing, Bogotá, Hong Kong, Jerusalem, London, Mexico City, Nairobi, New Delhi and Tokyo. In November 2009, it announced the closure of its U. S. regional bureaus—Chicago, Los Angeles and New York—as part of an increased focus on "political stories and local news coverage in Washington." The newspaper has local bureaus in Virginia. As of May 2013, its average weekday circulation was 474,767, according to the Audit Bureau of Circulations, making it the seventh largest newspaper in the country by circulation, behind USA Today, The Wall Street Journal, The New York Times, the Los Angeles Times, the Daily News, the New York Post. While its circulation has been slipping, it has one of the highest market-penetration rates of any metropolitan news daily. For many decades, the Post had its main office at 1150 15th Street NW; this real estate remained with Graham Holdings when the newspaper was sold to Jeff Bezos' Nash Holdings in 2013.
Graham Holdings sold 1150 15th Street for US$159 million in November 2013. The Washington Post continued to lease space at 1150 L Street NW. In May 2014, The Washington Post leased the west tower of One Franklin Square, a high-rise building at 1301 K Street NW in Washington, D. C; the newspaper moved into their new offices December 14, 2015. The Post has its own exclusive zip code, 20071. Arc Publishing is a department of the Post, which provides the publishing system, software for news organizations such as the Chicago Tribune and the Los Angeles Times; the newspaper was founded in 1877 by Stilson Hutchins and in 1880 added a Sunday edition, becoming the city's first newspaper to publish seven days a week. In 1889, Hutchins sold the newspaper to Frank Hatton, a former Postmaster General, Beriah Wilkins, a former Democratic congressman from Ohio. To promote the newspaper, the new owners requested the leader of the United States Marine Band, John Philip Sousa, to compose a march for the newspaper's essay contest awards ceremony.
Sousa composed "The Washington Post". It became the standard music to accompany the two-step, a late 19th-century dance craze, remains one of Sousa's best-known works. In 1893, the newspaper moved to a building at 14th and E streets NW, where it would remain until 1950; this building combined all functions of the newspaper into one headquarters – newsroom, advertising and printing – that ran 24 hours per day. In 1898, during the Spanish–American War, the Post printed Clifford K. Berryman's classic illustration Remember the Maine, which became the battle-cry for American sailors during the War. In 1902, Berryman published another famous cartoon in the Post—Drawing the Line in Mississippi; this cartoon depicts President Theodore Roosevelt showing compassion for a small bear cub and inspired New York store owner Morris Michtom to create the teddy bear. Wilkins acquired Hatton's share of the newspaper in 1894 at Hatton's death. After Wilkins' death in 1903, his sons John and Robert ran the Post for two years before selling it in 1905 to John Roll McLean, owner of the Cincinnati Enquirer.
During the Wilson presidency, the Post was credited with the "most famous newspaper typo" in D. C. history according to Reason magazine. When John McLean died in 1916, he put the newspap