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
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
In blood, the serum is the component, neither a blood cell, nor a clotting factor. Serum includes all proteins not used in blood clotting and all the electrolytes, antigens and any exogenous substances; the study of serum is serology. Serum is used in numerous diagnostic tests, as well as blood typing. Measurements of serum concentrations has proved useful in many fields including clinical trials of therapeutic vs toxic response. Blood is centrifuged to remove cellular components. Anti-coagulated blood yields plasma containing clotting factors. Coagulated blood yields serum without fibrinogen. Serum is an essential factor for the self-renewal of embryonic stem cells in combination with the cytokine leukemia inhibitory factor; the serum of convalescent patients recovering from an infectious disease can be used as a biopharmaceutical in the treatment of other people with that disease, because the antibodies generated by the successful recovery are potent fighters of the pathogen. Such convalescent serum is a form of immunotherapy.
Blood serum and plasma are some of the largest sources of biomarkers, whether for diagnostics or therapeutics. Its vast dynamic range, further complicated by the presence of lipids and post-translational modifications, as well multiple mechanisms of degradation, presents challenges in analytical reproducibility, sensitivity and potential efficacy. For analysis of biomarkers in blood serum samples, it is possible to do a pre-separation by free-flow electrophoresis that consists of a depletion of serum albumin protein; this method enables greater penetration of the proteome via separation of a wide variety of charged or chargeable analytes, ranging from small molecules to cells. Like many other mass nouns, the word serum can be pluralized. To speak of multiple serum specimens from multiple people, physicians sometimes speak of sera. Blood
Bornholm is a Danish island in the Baltic Sea, to the east of the rest of Denmark, south of Sweden, northeast of Germany and north of the westernmost part of Poland. Occupying an area of 588.36 square kilometres, the island had a total population on 1 January 2019 of 39,572. Among Bornholm's chief industrial activities are dairy farming and arts and crafts industries such as glass production and pottery using locally worked clay. Tourism is important during the summer months; the island is home to an large number of Denmark's round churches. The island is known as solskinsøen because of its weather and klippeøen because of its geology, which consists of granite, except along the southern coast; the heat from the summer is stored in the rock formations and the weather is quite warm until October. As a result of the climate, a local variety of the common fig, known as Bornholm's Diamond, can grow locally on the island; the island's topography consists of dramatic rock formations in the north sloping down towards pine and deciduous forests, farmland in the middle and sandy beaches in the south.
Strategically located in the Baltic Sea, Bornholm has been fought over for centuries. It had been ruled by Denmark, but by Sweden and Lübeck, Germany; the ruin of Hammershus, at the northwestern tip of the island, is the largest medieval fortress in northern Europe, testament to the importance of its location. This island and Ertholmene is what remains in Denmark of Skåneland east of Øresund, having been surrendered to Sweden in 1658 but with Bornholm after a local revolt regained in 1660. Many inhabitants speak the Bornholmsk dialect, a dialect of Danish. Bornholmsk retains three grammatical genders, like Icelandic and most dialects of Norwegian, but unlike standard Danish, its phonology includes innovations. This makes the dialect difficult to understand for some Danish speakers. However, Swedish speakers consider Bornholmian to be easier to understand than standard Danish; the intonation resembles the Scanian dialect spoken in nearby Scania, the southernmost province of Sweden. Bornholm Regional Municipality is the local authority covering the entire island.
It is the result of a merger of the five former municipalities on the island and the former Bornholm County. Bornholm Regional Municipality was a county in its own right during its first four years from 1 January 2003 until 31 December 2006. From 1 January 2007 all counties were abolished, Bornholm became part of the Capital Region of Denmark whose main responsibility is the health service; the municipality still retains its name Bornholm Regional Municipality. The island had 21 municipalities until March 1970, of which 6 were 15 parishes. In addition to supervising parish municipalities, the responsibility of the counties in all of Denmark, the market town municipalities of Bornholm were supervised by Bornholm County as well and not by the Interior Ministry as was the case in the rest of Denmark; the seat of the municipal council is Rønne. The voters decided to merge the county with the municipalities in a referendum May 29, 2001, effective from January 1, 2003; the question on the ballot was, "Do you want the six municipal entities of Bornholm to be joined to form one municipal entity as of 1 January 2003?"
73.9% voted in favour. The lowest percentage for the merger was in Nexø municipality, whose mayor, Annelise Molin, a Social Democrat, spoke out against the merger, it was required. Otherwise the merger would have to be abandoned altogether; the six municipal entities had 122 councillors and the new regional municipality would have 27 councillors from the start. They were reduced to 23 from 1 January 2018; the merger was approved in a law by the Folketing 19 March 2002, transferring the tasks of the abolished county and old municipalities to the new Bornholm Regional Municipality. The first regional mayor in the first three years from 2003 until 2005 was Thomas Thors, a physician and member of the Social Democrats and the last mayor of Rønne Municipality for five years from 1998 until 2002. Bjarne Kristiansen, the last mayor of Hasle 2½ years from the summer of 2000 until 2002, representing the local Borgerlisten political party, served as mayor for four years from January 1, 2006 until 2009. From January 1, 2007, Bornholm became a part of the Capital Region of Denmark.
From January 1, 2010 the mayor has been Winni Grosbøll, a high school teacher and a member of the Social Democrats political party. Ferry services connect Rønne to Świnoujście, Sassnitz, Køge, 45 kilometres by road south of Copenhagen, Denmark. Simrishamn has a ferry connection during the summer. There are regular catamaran services between Nexø and the Polish ports of Kołobrzeg, Łeba and Ustka. There are direct bus connections Ystad-Copenhagen, coordinated with the catamaran. There are flights from Bornholm Airport to Copenhagen and other locations; because of
Denmark the Kingdom of Denmark, is a Nordic country and the southernmost of the Scandinavian nations. Denmark lies southwest of Sweden and south of Norway, is bordered to the south by Germany; the Kingdom of Denmark comprises two autonomous constituent countries in the North Atlantic Ocean: the Faroe Islands and Greenland. Denmark proper consists of a peninsula, an archipelago of 443 named islands, with the largest being Zealand and the North Jutlandic Island; the islands are characterised by flat, arable land and sandy coasts, low elevation and a temperate climate. Denmark has a total area of 42,924 km2, land area of 42,394 km2, the total area including Greenland and the Faroe Islands is 2,210,579 km2, a population of 5.8 million. The unified kingdom of Denmark emerged in the 10th century as a proficient seafaring nation in the struggle for control of the Baltic Sea. Denmark and Norway were ruled together under one sovereign ruler in the Kalmar Union, established in 1397 and ending with Swedish secession in 1523.
The areas of Denmark and Norway remained under the same monarch until Denmark -- Norway. Beginning in the 17th century, there were several devastating wars with the Swedish Empire, ending with large cessions of territory to Sweden. After the Napoleonic Wars, Norway was ceded to Sweden, while Denmark kept the Faroe Islands and Iceland. In the 19th century there was a surge of nationalist movements, which were defeated in the 1864 Second Schleswig War. Denmark remained neutral during World War I. In April 1940, a German invasion saw brief military skirmishes while the Danish resistance movement was active from 1943 until the German surrender in May 1945. An industrialised exporter of agricultural produce in the second half of the 19th century, Denmark introduced social and labour-market reforms in the early 20th century that created the basis for the present welfare state model with a developed mixed economy; the Constitution of Denmark was signed on 5 June 1849, ending the absolute monarchy, which had begun in 1660.
It establishes a constitutional monarchy organised as a parliamentary democracy. The government and national parliament are seated in Copenhagen, the nation's capital, largest city, main commercial centre. Denmark exercises hegemonic influence in the Danish Realm, devolving powers to handle internal affairs. Home rule was established in the Faroe Islands in 1948. Denmark negotiated certain opt-outs, it is among the founding members of NATO, the Nordic Council, the OECD, OSCE, the United Nations. Denmark is considered to be one of the most economically and developed countries in the world. Danes enjoy a high standard of living and the country ranks in some metrics of national performance, including education, health care, protection of civil liberties, democratic governance and human development; the country ranks as having the world's highest social mobility, a high level of income equality, is among the countries with the lowest perceived levels of corruption in the world, the eleventh-most developed in the world, has one of the world's highest per capita incomes, one of the world's highest personal income tax rates.
The etymology of the word Denmark, the relationship between Danes and Denmark and the unifying of Denmark as one kingdom, is a subject which attracts debate. This is centered on the prefix "Dan" and whether it refers to the Dani or a historical person Dan and the exact meaning of the -"mark" ending. Most handbooks derive the first part of the word, the name of the people, from a word meaning "flat land", related to German Tenne "threshing floor", English den "cave"; the -mark is believed to mean woodland or borderland, with probable references to the border forests in south Schleswig. The first recorded use of the word Danmark within Denmark itself is found on the two Jelling stones, which are runestones believed to have been erected by Gorm the Old and Harald Bluetooth; the larger stone of the two is popularly cited as Denmark's "baptismal certificate", though both use the word "Denmark", in the form of accusative ᛏᛅᚾᛘᛅᚢᚱᚴ tanmaurk on the large stone, genitive ᛏᛅᚾᛘᛅᚱᚴᛅᚱ "tanmarkar" on the small stone.
The inhabitants of Denmark are there called "Danes", in the accusative. The earliest archaeological findings in Denmark date back to the Eem interglacial period from 130,000–110,000 BC. Denmark has been inhabited since around 12,500 BC and agriculture has been evident since 3900 BC; the Nordic Bronze Age in Denmark was marked by burial mounds, which left an abundance of findings including lurs and the Sun Chariot. During the Pre-Roman Iron Age, native groups began migrating south, the first tribal Danes came to the country between the Pre-Roman and the Germanic Iron Age, in the Roman Iron Age; the Roman provinces maintained trade routes and relations with native tribes in Denmark, Roman coins have been found in Denmark. Evidence of strong Celtic cultural influence dates from this period in Denmark and much of North-West Europe and is among other things reflected in the finding of the Gundestrup cauldron; the tribal Danes came from the east Danish islands and Scania and spoke an early form of North Germanic.
Historians believe that before their arrival, most of Jutland and the nearest islands were settled by tribal J