Celtic tribes settled in Switzerland between 1000 to 1500 BC. The Raetians lived in the eastern regions, while the west was occupied by the Helvetii and the Allobrogi settled in the Rhone valley and in Savoy. Among the many substances Celtic tribes mined was salt in areas such as Salzburg in Austria where evidence of the Hallstatt culture was found by a mine manager in the 19th century. By the 6th century BC the La Tène culture was well established in the region, and became known for high quality decorated weapons and jewelry. The Celts were the most widespread of the mountain tribes—they had warriors that were strong, tall and fair skinned skilled with iron weapons, which gave them an advantage in warfare.


During the Second Punic War in 218 BC, the Carthaginian general Hannibal probably crossed the Alps with an army numbering 38,000 infantry, 8,000 cavalry, and 37 war elephants. This was one of the most celebrated achievements of any military force in ancient warfare, although no evidence exists of the actual crossing or the place of crossing. The Romans, however, had built roads along the mountain passes, which continued to be used through the medieval period to cross the mountains and Roman road markers can still be found on the mountain passes.


The Roman expansion brought the defeat of the Allobrogi in 121 BC and during the Gallic Wars in 58 BC Julius Caesar overcame the Helvetii. The Rhaetians continued to resist but were eventually conquered when the Romans turned northward to the Danube valley in Austria and defeated the Brigantes. The Romans built settlements in the Alps; towns such as Aosta (named for Augustus) in Italy, Martigny and Lausanne in Switzerland, and Partenkirchen in Bavaria show remains of Roman baths, villas, arenas and temples. Much of the Alpine region was gradually settled by Germanic tribes, (Lombards, Alemanni, Bavarii, and Franks) from the 6th to the 13th centuries mixing with the local Celtic tribes.


Christianity was established in the region by the Romans, and saw the establishment of monasteries and churches in the high regions. The Frankish expansion of the Carolingian Empire and the Bavarian expansion in the eastern Alps introduced feudalism and the building of castles to support the growing number of dukedoms and kingdoms. Castello del Buonconsiglio in Trento, Italy, still has intricate frescoes, excellent examples of Gothic art, in a tower room. In Switzerland, Château de Chillon is preserved as an example of medieval architecture.


Much of the medieval period was a time of power struggles between competing dynasties such as the House of Savoy, the Visconti in northern Italy and the House of Habsburg in Austria and Slovenia. In 1291 to protect themselves from incursions by the Habsburgs, four cantons in the middle of Switzerland drew up a charter that is considered to be a declaration of independence from neighboring kingdoms. After a series of battles fought in the 13th, 14th and 15th centuries, more cantons joined the confederacy and by the 16th century Switzerland was well-established as a separate state.


During the Napoleonic Wars in the late 18th century and early 19th century, Napoleon annexed territory formerly controlled by the Habsburgs and Savoys. In 1798 he established the Helvetic Republic in Switzerland; two years later he led an army across the St. Bernard pass and conquered almost all of the Alpine regions.


After the fall of Napoléon, many alpine countries developed heavy protections to prevent any new invasion. Thus, Savoy built a series of fortifications in the Maurienne valley in order to protect the major alpine passes, such as the col du Mont-Cenis that was even crossed by, Charlemagne and his father to defeat the Lombarts. The later indeed became very popular after the construction of a paved road ordered by Napoléon Bonaparte. The Barrière de l'Esseillon is a serie of forts with heavy batteries, built on a cliff with a perfect view on the valley, a gorge on one side and steep mountains on the other side.


In the 19th century, the monasteries built in the high Alps during the medieval period to shelter travelers and as places of pilgrimage, became tourist destinations. The Benedictines had built monasteries in Lucerne, Switzerland, and Oberammergau; the Cistercians in the Tyrol and at Lake Constance; and the Augustinians had abbeys in the Savoy and one in the center of Interlaken, Switzerland. The Great St Bernard Hospice, built in the 9th or 10th centuries, at the summit of the Great Saint Bernard Pass was shelter for travelers and place for pilgrims since its inception; by the 19th century it became a tourist attraction with notable visitors such as author Charles Dickens and mountaineer Edward Whymper.


Radiocarbon dated charcoal placed around 50,000 years ago was found in the Drachloch (Dragon's Hole) cave above the village of Vattis in the canton of St. Gallen, proving that the high peaks were visited by prehistoric people. Seven bear skulls from the cave may have been buried by the same prehistoric people. The peaks, however, were mostly ignored except for a few notable examples, and long left to the exclusive attention of the people of the adjoining valleys. The mountain peaks were seen as terrifying, the abode of dragons and demons, to the point that people blindfolded themselves to cross the Alpine passes. The glaciers remained a mystery and many still believed the highest areas to be inhabited by dragons.


Charles VII of France ordered his chamberlain to climb Mont Aiguille in 1356. The knight reached the summit of Rocciamelone where he left a bronze triptych of three crosses, a feat which he conducted with the use of ladders to traverse the ice. In 1492 Antoine de Ville climbed Mont Aiguille, without reaching the summit, an experience he described as "horrifying and terrifying." Leonardo da Vinci was fascinated by variations of light in the higher altitudes, and climbed a mountain—scholars are uncertain which one; some believe it may have been Monte Rosa. From his description of a "blue like that of a gentian" sky it is thought that he reached a significantly high altitude. In the 18th century four Chamonix man almost made the summit of Mont Blanc but were overcome by altitude sickness and snowblindness.


Conrad Gessner was the first naturalist to ascend the mountains in the 16th century, to study them, writing that in the mountains he found the "theatre of the Lord". By the 19th century more naturalists began to arrive to explore, study and conquer the high peaks; they were followed by artists, writers and painters. Two men who first explored the regions of ice and snow were Horace-Bénédict de Saussure (1740–1799) in the Pennine Alps, and the Benedictine monk of Disentis Placidus a Spescha (1752–1833). Born in Geneva, Saussure was enamored with the mountains from an early age; he left a law career to become a naturalist and spent many years trekking through the Bernese Oberland, the Savoy, the Piedmont and Valais, studying the glaciers and the geology, as he became an early proponent of the theory of rock upheaval. Saussure, in 1787, was a member of the third ascent of Mont Blanc—today the summits of all the peaks have been climbed.


Jean-Jacques Rousseau was the first of many to present the Alps as a place of allure and beauty, banishing the prevalent conception of the mountains as a hellish wasteland inhabited by demons. Rousseau's conception of alpine purity was later emphasized with the publication of Albrecht von Haller's poem Die Alpen that described the mountains as an area of mythical purity. Late in the 18th century the first wave of Romantics such as Goethe and Turner came to admire the scenery; Wordsworth visited the area in 1790, writing of his experiences in The Prelude. Schiller later wrote the play William Tell romanticising Swiss independence. After the end of the Napoleonic Wars, the Alpine countries began to see an influx of poets, artists, and musicians, as visitors came to experience the sublime effects of monumental nature.


In 1816 Byron, Percy Bysshe Shelley and his wife Mary Shelley visited Geneva and all three were inspired by the scenery in their writings. During these visits Shelley wrote the poem "Mont Blanc", Byron wrote "The Prisoner of Chillon" and the dramatic poem Manfred, and Mary Shelley, who found the scenery overwhelming, conceived the idea for the novel Frankenstein in her villa on the shores of Lake Geneva in the midst of a thunderstorm. When Coleridge travelled to Chamonix, he declaimed, in defiance of Shelley, who had signed himself "Atheos" in the guestbook of the Hotel de Londres near Montenvers, "Who would be, who could be an atheist in this valley of wonders". By the mid-19th century scientists began to arrive en masse to study the geology and ecology of the region.


Austrian-born Adolf Hitler had a lifelong romantic fascination with the Alps and by the 1930s established a home in the Obersalzberg region outside of Berchtesgaden. His first visit to the area was in 1923 and he maintained a strong tie there until the end of his life. At the end of World War II the US Army occupied Obersalzberg, to prevent Hitler from retreating with the Wehrmacht into the mountains.


By 1940 the Third Reich had occupied many of the Alpine countries. Austria underwent a political coup that made it part of the Third Reich; France had been invaded and Italy was a fascist regime. Switzerland was the only country to luckily avoid invasion. The Swiss Confederate mobilized its troops—the country follows the doctrine of "armed neutrality" with all males required to have military training—a number that General Eisenhower estimated to be about 850,000. The Swiss commanders wired the infrastructure leading into the country, and threatening to destroy bridges, railway tunnels and passes in the event of a Nazi invasion, and then they retreated to the heart of the mountain peaks where conditions were harsher and a military invasion would involve difficult and protracted battles.


Ski troops were trained for the war, and battles were waged in mountainous areas such as the battle at Riva Ridge in Italy, where the American 10th Mountain Division encountered heavy resistance in February 1945. At the end of the war, a substantial amount of Nazi plunder was found stored in Austria, where Hitler had hoped to retreat as the war drew to a close. The salt mines surrounding the Altaussee area, where American troops found 75 kilos of gold coins stored in a single mine, were used to store looted art, jewels, and currency; vast quantities of looted art were found and returned to the owners.


The population of the region is 14 million spread across eight countries. On the rim of the mountains, on the plateaus and the plains the economy consists of manufacturing and service jobs whereas in the higher altitudes and in the mountains farming is still essential to the economy. Farming and forestry continue to be mainstays of Alpine culture, industries that provide for export to the cities and maintain the mountain ecology.


Much of the Alpine culture is unchanged since the medieval period when skills that guaranteed survival in the mountain valleys and in the highest villages became mainstays, leading to strong traditions of carpentry, woodcarving, baking and pastry-making, and cheesemaking.


Farming had been a traditional occupation for centuries, although it became less dominant in the 20th century with the advent of tourism. Grazing and pasture land are limited because of the steep and rocky topography of the Alps. In mid-June cows are moved to the highest pastures close to the snowline, where they are watched by herdsmen who stay in the high altitudes often living in stone huts or wooden barns during the summers. Villagers celebrate the day the cows are herded up to the pastures and again when they return in mid-September. The Alpanschluss or Désalpes ("coming down from the alps") is celebrated by decorating the cows with garlands and enormous cowbells while the farmers dress in traditional costumes.


Cheesemaking is an ancient tradition in most Alpine countries. A wheel of cheese from the Emmental in Switzerland can weigh up to 45 kg (100 lb), and the Beaufort in Savoy can weight up to 70 kilograms (150 lb). Owners of the cows traditionally receive from the cheesemakers a portion in relation to the proportion of the cows' milk from the summer months in the high alps. Haymaking is an important farming activity in mountain villages which has become somewhat mechanized in recent years, although the slopes are so steep that usually scythes are necessary to cut the grass. Hay is normally brought in twice a year, often also on festival days. Alpine festivals vary from country to country and often include the display of local costumes such as dirndl and trachten, the playing of Alpenhorns, wrestling matches, some pagan traditions such as Walpurgis Night and, in many areas, Carnival is celebrated before Lent.


In the high villages people live in homes built according to medieval designs that withstand cold winters. The kitchen is separated from the living area (called the stube, the area of the home heated by a stove), and second-floor bedrooms benefit from rising heat. The typical Swiss chalet originated in the Bernese Oberland. Chalets often face south or downhill, and are built of solid wood, with a steeply gabled roof to allow accumulated snow to slide off easily. Stairs leading to upper levels are sometimes built on the outside, and balconies are sometimes enclosed.


Food is passed from the kitchen to the stube, where the dining room table is placed. Some meals are communal, such as fondue, where a pot is set in the middle of the table for each person to dip into. Other meals are still served in a traditional manner on carved wooden plates. Furniture has been traditionally elaborately carved and in many Alpine countries carpentry skills are passed from generation to generation.


Roofs are traditionally constructed from Alpine rocks such as pieces of schist, gneiss or slate. Such chalets are typically found in the higher parts of the valleys, as in the Maurienne valley in Savoy, where the amount of snow during the cold months is important. The inclination of the roof cannot exceed 40%, allowing the snow to stay on top, thereby functioning as insulation from the cold. In the lower areas where the forests are widespread, wooden tiles are traditionally used. Commonly made of Norway spruce, they are called "tavaillon". The Alpine regions are multicultural and linguistically diverse. Dialects are common, and vary from valley to valley and region to region. In the Slavic Alps alone 19 dialects have been identified. Some of the French dialects spoken in the French, Swiss and Italian alps of Aosta Valley derive from Arpitan, while the southern part of the western range is related to Old Provençal; the German dialects derive from Germanic tribal languages. Romansh, spoken by two percent of the population in southeast Switzerland, is an ancient Rhaeto-Romanic language derived from Latin, remnants of ancient Celtic languages and perhaps Etruscan.


At present the Alps are one of the more popular tourist destinations in the world with many resorts such Oberstdorf, in Bavaria, Saalbach in Austria, Davos in Switzerland, Chamonix in France, and Cortina d'Ampezzo in Italy recording more than a million annual visitors. With over 120 million visitors a year tourism is integral to the Alpine economy with much it coming from winter sports although summer visitors are an important component of the tourism industry.


The tourism industry began in the early 19th century when foreigners visited the Alps, traveled to the bases of the mountains to enjoy the scenery, and stayed at the spa-resorts. Large hotels were built during the Belle Époque; cog-railways, built early in the 20th century, brought tourists to ever higher elevations, with the Jungfraubahn terminating at the Jungfraujoch, well above the eternal snow-line, after going through a tunnel in Eiger. During this period winter sports were slowly introduced: in 1882 the first figure skating championship was held in St. Moritz, and downhill skiing became a popular sport with English visitors early in the 20th century, as the first ski-lift was installed in 1908 above Grindelwald.


In the first half of the 20th century the Olympic Winter Games were held three times in Alpine venues: the 1924 Winter Olympics in Chamonix, France; the 1928 Winter Olympics in St. Moritz, Switzerland; and the 1936 Winter Olympics in Garmisch-Partenkirchen, Germany. During World War II the winter games were canceled but after that time the Winter Games have been held in St. Moritz (1948), Cortina d'Ampezzo (1956), Innsbruck, Austria (1964 and 1976), Grenoble, France, (1968), Albertville, France, (1992), and Torino (2006). In 1930 the Lauberhorn Rennen (Lauberhorn Race), was run for the first time on the Lauberhorn above Wengen; the equally demanding Hahnenkamm was first run in the same year in Kitzbühl, Austria. Both races continue to be held each January on successive weekends. The Lauberhorn is the more strenuous downhill race at 4.5 km (2.8 mi) and poses danger to racers who reach 130 km/h (81 mph) within seconds of leaving the start gate.


During the post-World War I period ski-lifts were built in Swiss and Austrian towns to accommodate winter visitors, but summer tourism continued to be important; by the mid-20th century the popularity of downhill skiing increased greatly as it became more accessible and in the 1970s several new villages were built in France devoted almost exclusively to skiing, such as Les Menuires. Until this point Austria and Switzerland had been the traditional and more popular destinations for winter sports, but by the end of the 20th century and into the early 21st century, France, Italy and the Tyrol began to see increases in winter visitors. From 1980 to the present, ski-lifts have been modernized and snow-making machines installed at many resorts, leading to concerns regarding the loss of traditional Alpine culture and questions regarding sustainable development as the winter ski industry continues to develop quickly and the number of summer tourists decline.


The region is serviced by 4,200 km (2,600 mi) of roads used by 6 million vehicles. Train travel is well established in the Alps, with, for instance 120 km (75 mi) of track for every 1,000 km2 (390 sq mi) in a country such as Switzerland. Most of Europe's highest railways are located there. Moreover, plans are underway to build a 57 km (35 mi)-long sub-alpine tunnel connecting the older Lötschberg and Gotthard tunnels built in the 19th century.


Some high mountain villages, such as Avoriaz (in France), Wengen, and Zermatt (in Switzerland) are accessible only by cable car or cog-rail trains, and are car free. Other villages in the Alps are considering becoming car free zones or limiting the number of cars for reasons of sustainability of the fragile Alpine terrain.


The lower regions and larger towns of the Alps are well-served by motorways and main roads, but higher mountain passes and byroads, which are amongst the highest in Europe, can be treacherous even in summer due to steep slopes. Many passes are closed in winter. A multitude of airports around the Alps (and some within), as well as long-distance rail links from all neighbouring countries, afford large numbers of travellers easy access from abroad.


A gene is a locus (or region) of DNA that encodes a functional RNA or protein product, and is the molecular unit of heredity.:Glossary The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic traits. Most biological traits are under the influence of polygenes (many different genes) as well as the gene–environment interactions. Some genetic traits are instantly visible, such as eye colour or number of limbs, and some are not, such as blood type, risk for specific diseases, or the thousands of basic biochemical processes that comprise life.


Genes can acquire mutations in their sequence, leading to different variants, known as alleles, in the population. These alleles encode slightly different versions of a protein, which cause different phenotype traits. Colloquial usage of the term "having a gene" (e.g., "good genes," "hair colour gene") typically refers to having a different allele of the gene. Genes evolve due to natural selection or survival of the fittest of the alleles.


The concept of a gene continues to be refined as new phenomena are discovered. For example, regulatory regions of a gene can be far removed from its coding regions, and 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 existence of discrete inheritable units was first suggested by Gregor Mendel (1822–1884). From 1857 to 1864, 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 the distinction between genotype (the genetic material of an organism) and phenotype (the visible traits of that organism). Mendel was also the first to demonstrate independent assortment, the distinction between dominant and recessive traits, the distinction between a heterozygote and homozygote, and 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, which used the term gemmule to describe hypothetical particles that would mix during reproduction. Although Mendel's work was largely unrecognized after its first publication in 1866, it was 'rediscovered' in 1900 by three European scientists, Hugo de Vries, Carl Correns, and Erich von Tschermak, who claimed to have reached similar conclusions in their own research.


The word gene is derived (via pangene) from the Ancient Greek word γένος (génos) meaning "race, offspring". Gene was coined in 1909 by Danish botanist Wilhelm Johannsen to describe the fundamental physical and functional unit of heredity, while the related word genetics was first used by William Bateson in 1905.


Advances in understanding genes and inheritance continued throughout the 20th century. Deoxyribonucleic acid (DNA) 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 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. Collectively, this body of research established the central dogma of molecular biology, which states that proteins are translated from RNA, which is 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 at the University of Ghent were the first to determine the sequence of a gene: the gene for 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 Human Genome Project.


The theories developed in the 1930s and 1940s to integrate molecular genetics with Darwinian evolution are called the modern evolutionary synthesis, a term introduced by Julian Huxley. Evolutionary biologists subsequently refined this concept, such as George C. Williams' gene-centric view of evolution. He proposed an evolutionary concept of the gene as a unit of natural selection with the definition: "that which segregates and recombines with appreciable frequency.":24 In this view, the molecular gene transcribes as a unit, and the evolutionary gene inherits as a unit. Related ideas emphasizing the centrality of genes in evolution were popularized by Richard Dawkins.


The vast majority of living organisms encode their genes in long strands of DNA (deoxyribonucleic acid). DNA consists of a chain made from four types of nucleotide subunits, each composed of: a five-carbon sugar (2'-deoxyribose), a phosphate group, and one of the four bases adenine, cytosine, guanine, and thymine.:2.1


Two chains of DNA twist around each other to form a DNA double helix with the phosphate-sugar backbone spiralling around the outside, and the bases pointing inwards with adenine base pairing to thymine and guanine to cytosine. The specificity of base pairing occurs because adenine and thymine align form two hydrogen bonds, whereas cytosine and guanine form three hydrogen bonds. The two strands in a double helix must therefore be complementary, with their sequence of bases matching such that the adenines of one strand are paired with the thymines of the other strand, and so on.:4.1


Due to the chemical composition of the pentose residues of the bases, DNA strands have directionality. One end of a DNA polymer contains an exposed hydroxyl group on the deoxyribose; this is known as the 3' end of the molecule. The other end contains an exposed phosphate group; this is the 5' end. The two strands of a double-helix run in opposite directions. Nucleic acid synthesis, including DNA replication and transcription occurs in the 5'→3' direction, because new nucleotides are added via a dehydration reaction that uses the exposed 3' hydroxyl as a nucleophile.:27.2


The expression of genes encoded in DNA begins by transcribing the gene into RNA, a second type of nucleic acid that is very similar to DNA, but whose monomers contain the sugar ribose rather than deoxyribose. RNA also contains the base uracil in place of thymine. RNA molecules are less stable than DNA and are typically single-stranded. Genes that encode proteins are composed of a series of three-nucleotide sequences called codons, which serve as the "words" in the genetic "language". The genetic code specifies the correspondence during protein translation between codons and amino acids. The genetic code is nearly the same for all known organisms.:4.1


The total complement of genes in an organism or cell is known as its genome, which may be stored on one or more chromosomes. A chromosome consists of a single, very long DNA helix on which thousands of genes are encoded.:4.2 The region of the chromosome at which a particular gene is located is called its locus. Each locus contains one allele of a gene; however, members of a population may have different alleles at the locus, each with a slightly different gene sequence.


The majority of eukaryotic genes are stored on a set of large, linear chromosomes. The chromosomes are packed within the nucleus in complex with storage proteins called histones to form a unit called a nucleosome. DNA packaged and condensed in this way is called chromatin.:4.2 The manner in which DNA is stored on the histones, as well as chemical modifications of the histone itself, regulate whether a particular region of DNA is accessible for gene expression. In addition to genes, eukaryotic chromosomes contain sequences involved in ensuring that the DNA is copied without degradation of end regions and sorted into daughter cells during cell division: replication origins, telomeres and the centromere.:4.2 Replication origins are the sequence regions where DNA replication is initiated to make two copies of the chromosome. Telomeres are long stretches of repetitive sequence that cap the ends of the linear chromosomes and prevent degradation of coding and regulatory regions during DNA replication. The length of the telomeres decreases each time the genome is replicated and has been implicated in the aging process. The centromere is required for binding spindle fibres to separate sister chromatids into daughter cells during cell division.:18.2


Prokaryotes (bacteria and archaea) typically store their genomes on a single large, circular chromosome. Similarly, some eukaryotic organelles contain a remnant circular chromosome with a small number of genes.:14.4 Prokaryotes sometimes supplement their chromosome with additional small circles of DNA called plasmids, which usually encode only a few genes and are transferable between individuals. For example, the genes for antibiotic resistance are usually encoded on bacterial plasmids and can be passed between individual cells, even those of different species, via horizontal gene transfer.


Whereas the chromosomes of prokaryotes are relatively gene-dense, those of eukaryotes often contain regions of DNA that serve no obvious function. Simple single-celled eukaryotes have relatively small amounts of such DNA, whereas the genomes of complex multicellular organisms, including humans, contain an absolute majority of DNA without an identified function. This DNA has often been referred to as "junk DNA". However, more recent analyses suggest that, although protein-coding DNA makes up barely 2% of the human genome, about 80% of the bases in the genome may be expressed, so the term "junk DNA" may be a misnomer.


The structure of a gene consists of many elements of which the actual protein coding sequence is often only a small part. These include DNA regions that are not transcribed as well as untranslated regions of the RNA.


Firstly, flanking the open reading frame, all genes contain a regulatory sequence that is required for their expression. In order to be expressed, genes require a promoter sequence. The promoter is recognized and bound by transcription factors and RNA polymerase to initiate transcription.:7.1 A gene can have more than one promoter, resulting in messenger RNAs (mRNA) that differ in how far they extend in the 5' end. Promoter regions have a consensus sequence, however highly transcribed genes have "strong" promoter sequences that bind the transcription machinery well, whereas others have "weak" promoters that bind poorly and initiate transcription less frequently.:7.2 Eukaryotic promoter regions are much more complex and difficult to identify than prokaryotic promoters.:7.3


Additionally, genes can have regulatory regions many kilobases upstream or downstream of the open reading frame. These act by binding to transcription factors which then cause the DNA to loop so that the regulatory sequence (and bound transcription factor) become close to the RNA polymerase binding site. For example, enhancers increase transcription by binding an activator protein which then helps to recruit the RNA polymerase to the promoter; conversely silencers bind repressor proteins and make the DNA less available for RNA polymerase.


The transcribed pre-mRNA contains untranslated regions at both ends which contain a ribosome binding site, terminator and start and stop codons. In addition, most eukaryotic open reading frames contain untranslated introns which are removed before the exons are translated. The sequences at the ends of the introns, dictate the splice sites to generate the final mature mRNA which encodes the protein or RNA product.


Many prokaryotic genes are organized into operons, with multiple protein-coding sequences that are transcribed as a unit. The products of operon genes typically have related functions and are involved in the same regulatory network.:7.3


Defining exactly what section of a DNA sequence comprises a gene is difficult. Regulatory regions of a gene such as enhancers do not necessarily have to be close to the coding sequence on the linear molecule because the intervening DNA can be looped out to bring the gene and its regulatory region into proximity. Similarly, a gene's introns can be much larger than its exons. Regulatory regions can even be on entirely different chromosomes and operate in trans to allow regulatory regions on one chromosome to come in contact with target genes on another chromosome.


Early work in molecular genetics suggested the model that one gene makes one protein. This model has been refined since the discovery of genes that can encode multiple proteins by alternative splicing and coding sequences split in short section across the genome whose mRNAs are concatenated by trans-splicing.


A broad operational definition is sometimes used to encompass the complexity of these diverse phenomena, where a gene is defined as a union of genomic sequences encoding a coherent set of potentially overlapping functional products. This definition categorizes genes by their functional products (proteins or RNA) rather than their specific DNA loci, with regulatory elements classified as gene-associated regions.


In all organisms, two steps are required to read the information encoded in a gene's DNA and produce the protein it specifies. First, the gene's DNA is transcribed to messenger RNA (mRNA).:6.1 Second, that mRNA is translated to protein.:6.2 RNA-coding genes must still go through the first step, but are not translated into protein. The process of producing a biologically functional molecule of either RNA or protein is called gene expression, and the resulting molecule is called a gene product.


The nucleotide sequence of a gene's DNA specifies the amino acid sequence of a protein through the genetic code. Sets of three nucleotides, known as codons, each correspond to a specific amino acid.:6 Additionally, a "start codon", and three "stop codons" indicate the beginning and end of the protein coding region. There are 64 possible codons (four possible nucleotides at each of three positions, hence 43 possible codons) and only 20 standard amino acids; hence the code is redundant and multiple codons can specify the same amino acid. The correspondence between codons and amino acids is nearly universal among all known living organisms.


Transcription produces a single-stranded RNA molecule known as messenger RNA, whose nucleotide sequence is complementary to the DNA from which it was transcribed.:6.1 The mRNA acts as an intermediate between the DNA gene and its final protein product. The gene's DNA is used as a template to generate a complementary mRNA. The mRNA matches the sequence of the gene's DNA coding strand because it is synthesised as the complement of the template strand. Transcription is performed by an enzyme called an RNA polymerase, which reads the template strand in the 3' to 5' direction and synthesizes the RNA from 5' to 3'. To initiate transcription, the polymerase first recognizes and binds a promoter region of the gene. Thus, a major mechanism of gene regulation is the blocking or sequestering the promoter region, either by tight binding by repressor molecules that physically block the polymerase, or by organizing the DNA so that the promoter region is not accessible.:7


In prokaryotes, transcription occurs in the cytoplasm; for very long transcripts, translation may begin at the 5' end of the RNA while the 3' end is still being transcribed. In eukaryotes, transcription occurs in the nucleus, where the cell's DNA is stored. The RNA molecule produced by the polymerase is known as the primary transcript and undergoes post-transcriptional modifications before being exported to the cytoplasm for translation. One of the modifications performed is the splicing of introns which are sequences in the transcribed region that do not encode protein. Alternative splicing mechanisms can result in mature transcripts from the same gene having different sequences and thus coding for different proteins. This is a major form of regulation in eukaryotic cells and also occurs in some prokaryotes.:7.5


Translation is the process by which a mature mRNA molecule is used as a template for synthesizing a new protein.:6.2 Translation is carried out by ribosomes, large complexes of RNA and protein responsible for carrying out the chemical reactions to add new amino acids to a growing polypeptide chain by the formation of peptide bonds. The genetic code is read three nucleotides at a time, in units called codons, via interactions with specialized RNA molecules called transfer RNA (tRNA). Each tRNA has three unpaired bases known as the anticodon that are complementary to the codon it reads on the mRNA. The tRNA is also covalently attached to the amino acid specified by the complementary codon. When the tRNA binds to its complementary codon in an mRNA strand, the ribosome attaches its amino acid cargo to the new polypeptide chain, which is synthesized from amino terminus to carboxyl terminus. During and after synthesis, most new proteins must folds to their active three-dimensional structure before they can carry out their cellular functions.:3


Genes are regulated so that they are expressed only when the product is needed, since expression draws on limited resources.:7 A cell regulates its gene expression depending on its external environment (e.g. available nutrients, temperature and other stresses), its internal environment (e.g. cell division cycle, metabolism, infection status), and its specific role if in a multicellular organism. Gene expression can be regulated at any step: from transcriptional initiation, to RNA processing, to post-translational modification of the protein. The regulation of lactose metabolism genes in E. coli (lac operon) was the first such mechanism to be described in 1961.


A typical protein-coding gene is first copied into RNA as an intermediate in the manufacture of the final protein product.:6.1 In other cases, the RNA molecules are the actual functional products, as in the synthesis of ribosomal RNA and transfer RNA. Some RNAs known as ribozymes are capable of enzymatic function, and microRNA has a regulatory role. The DNA sequences from which such RNAs are transcribed are known as non-coding RNA genes.


Some viruses store their entire genomes in the form of RNA, and contain no DNA at all. Because they use RNA to store genes, their cellular hosts may synthesize their proteins as soon as they are infected and without the delay in waiting for transcription. On the other hand, RNA retroviruses, such as HIV, require the reverse transcription of their genome from RNA into DNA before their proteins can be synthesized. RNA-mediated epigenetic inheritance has also been observed in plants and very rarely in animals.


Organisms inherit their genes from their parents. Asexual organisms simply inherit a complete copy of their parent's genome. Sexual organisms have two copies of each chromosome because they inherit one complete set from each parent.:1


According to Mendelian inheritance, variations in an organism's phenotype (observable physical and behavioral characteristics) are due in part to variations in its genotype (particular set of genes). Each gene specifies a particular trait with different sequence of a gene (alleles) giving rise to different phenotypes. Most eukaryotic organisms (such as the pea plants Mendel worked on) have two alleles for each trait, one inherited from each parent.:20


Alleles at a locus may be dominant or recessive; dominant alleles give rise to their corresponding phenotypes when paired with any other allele for the same trait, whereas recessive alleles give rise to their corresponding phenotype only when paired with another copy of the same allele. For example, if the allele specifying tall stems in pea plants is dominant over the allele specifying short stems, then pea plants that inherit one tall allele from one parent and one short allele from the other parent will also have tall stems. Mendel's work demonstrated that alleles assort independently in the production of gametes, or germ cells, ensuring variation in the next generation. Although Mendelian inheritance remains a good model for many traits determined by single genes (including a number of well-known genetic disorders) it does not include the physical processes of DNA replication and cell division.


The growth, development, and reproduction of organisms relies on cell division, or the process by which a single cell divides into two usually identical daughter cells. This requires first making a duplicate copy of every gene in the genome in a process called DNA replication.:5.2 The copies are made by specialized enzymes known as DNA polymerases, which "read" one strand of the double-helical DNA, known as the template strand, and synthesize a new complementary strand. Because the DNA double helix is held together by base pairing, the sequence of one strand completely specifies the sequence of its complement; hence only one strand needs to be read by the enzyme to produce a faithful copy. The process of DNA replication is semiconservative; that is, the copy of the genome inherited by each daughter cell contains one original and one newly synthesized strand of DNA.:5.2


After DNA replication is complete, the cell must physically separate the two copies of the genome and divide into two distinct membrane-bound cells.:18.2 In prokaryotes (bacteria and archaea) this usually occurs via a relatively simple process called binary fission, in which each circular genome attaches to the cell membrane and is separated into the daughter cells as the membrane invaginates to split the cytoplasm into two membrane-bound portions. Binary fission is extremely fast compared to the rates of cell division in eukaryotes. Eukaryotic cell division is a more complex process known as the cell cycle; DNA replication occurs during a phase of this cycle known as S phase, whereas the process of segregating chromosomes and splitting the cytoplasm occurs during M phase.:18.1


The duplication and transmission of genetic material from one generation of cells to the next is the basis for molecular inheritance, and the link between the classical and molecular pictures of genes. Organisms inherit the characteristics of their parents because the cells of the offspring contain copies of the genes in their parents' cells. In asexually reproducing organisms, the offspring will be a genetic copy or clone of the parent organism. In sexually reproducing organisms, a specialized form of cell division called meiosis produces cells called gametes or germ cells that are haploid, or contain only one copy of each gene.:20.2 The gametes produced by females are called eggs or ova, and those produced by males are called sperm. Two gametes fuse to form a diploid fertilized egg, a single cell that has two sets of genes, with one copy of each gene from the mother and one from the father.:20


During the process of meiotic cell division, an event called genetic recombination or crossing-over can sometimes occur, in which a length of DNA on one chromatid is swapped with a length of DNA on the corresponding sister chromatid. This has no effect if the alleles on the chromatids are the same, but results in reassortment of otherwise linked alleles if they are different.:5.5 The Mendelian principle of independent assortment asserts that each of a parent's two genes for each trait will sort independently into gametes; which allele an organism inherits for one trait is unrelated to which allele it inherits for another trait. This is in fact only true for genes that do not reside on the same chromosome, or are located very far from one another on the same chromosome. The closer two genes lie on the same chromosome, the more closely they will be associated in gametes and the more often they will appear together; genes that are very close are essentially never separated because it is extremely unlikely that a crossover point will occur between them. This is known as genetic linkage.


DNA replication is for the most part extremely accurate, however errors (mutations) do occur.:7.6 The error rate in eukaryotic cells can be as low as 10−8 per nucleotide per replication, whereas for some RNA viruses it can be as high as 10−3. This means that each generation, each human genome accumulates 1–2 new mutations. Small mutations can be caused by DNA replication and the aftermath of DNA damage and include point mutations in which a single base is altered and frameshift mutations in which a single base is inserted or deleted. Either of these mutations can change the gene by missense (change a codon to encode a different amino acid) or nonsense (a premature stop codon). Larger mutations can be caused by errors in recombination to cause chromosomal abnormalities including the duplication, deletion, rearrangement or inversion of large sections of a chromosome. Additionally, the DNA repair mechanisms that normally revert mutations can introduce errors when repairing the physical damage to the molecule is more important than restoring an exact copy, for example when repairing double-strand breaks.:5.4


When multiple different alleles for a gene are present in a species's population it is called polymorphic. Most different alleles are functionally equivalent, however some alleles can give rise to different phenotypic traits. A gene's most common allele is called the wild type, and rare alleles are called mutants. The genetic variation in relative frequencies of different alleles in a population is due to both natural selection and genetic drift. The wild-type allele is not necessarily the ancestor of less common alleles, nor is it necessarily fitter.


Most mutations within genes are neutral, having no effect on the organism's phenotype (silent mutations). Some mutations do not change the amino acid sequence because multiple codons encode the same amino acid (synonymous mutations). Other mutations can be neutral if they lead to amino acid sequence changes, but the protein still functions similarly with the new amino acid (e.g. conservative mutations). Many mutations, however, are deleterious or even lethal, and are removed from populations by natural selection. Genetic disorders are the result of deleterious mutations and can be due to spontaneous mutation in the affected individual, or can be inherited. Finally, a small fraction of mutations are beneficial, improving the organism's fitness and are extremely important for evolution, since their directional selection leads to adaptive evolution.:7.6


Genes with a most recent common ancestor, and thus a shared evolutionary ancestry, are known as homologs. These genes appear either from gene duplication within an organism's genome, where they are known as paralogous genes, or are the result of divergence of the genes after a speciation event, where they are known as orthologous genes,:7.6 and often perform the same or similar functions in related organisms. It is often assumed that the functions of orthologous genes are more similar than those of paralogous genes, although the difference is minimal.


The relationship between genes can be measured by comparing the sequence alignment of their DNA.:7.6 The degree of sequence similarity between homologous genes is called conserved sequence. Most changes to a gene's sequence do not affect its function and so genes accumulate mutations over time by neutral molecular evolution. Additionally, any selection on a gene will cause its sequence to diverge at a different rate. Genes under stabilizing selection are constrained and so change more slowly whereas genes under directional selection change sequence more rapidly. The sequence differences between genes can be used for phylogenetic analyses to study how those genes have evolved and how the organisms they come from are related.


The most common source of new genes in eukaryotic lineages is gene duplication, which creates copy number variation of an existing gene in the genome. The resulting genes (paralogs) may then diverge in sequence and in function. Sets of genes formed in this way comprise a gene family. Gene duplications and losses within a family are common and represent a major source of evolutionary biodiversity. Sometimes, gene duplication may result in a nonfunctional copy of a gene, or a functional copy may be subject to mutations that result in loss of function; such nonfunctional genes are called pseudogenes.:7.6


De novo or "orphan" genes, whose sequence shows no similarity to existing genes, are extremely rare. Estimates of the number of de novo genes in the human genome range from 18 to 60. Such genes are typically shorter and simpler in structure than most eukaryotic genes, with few if any introns. Two primary sources of orphan protein-coding genes are gene duplication followed by extremely rapid sequence change, such that the original relationship is undetectable by sequence comparisons, and formation through mutation of "cryptic" transcription start sites that introduce a new open reading frame in a region of the genome that did not previously code for a protein.


Horizontal gene transfer refers to the transfer of genetic material through a mechanism other than reproduction. This mechanism is a common source of new genes in prokaryotes, sometimes thought to contribute more to genetic variation than gene duplication. It is a common means of spreading antibiotic resistance, virulence, and adaptive metabolic functions. Although horizontal gene transfer is rare in eukaryotes, likely examples have been identified of protist and alga genomes containing genes of bacterial origin.


The genome size, and the number of genes it encodes varies widely between organisms. The smallest genomes occur in viruses (which can have as few as 2 protein-coding genes), and viroids (which act as a single non-coding RNA gene). Conversely, plants can have extremely large genomes, with rice containing >46,000 protein-coding genes. The total number of protein-coding genes (the Earth's proteome) is estimated to be 5 million sequences.


Although the number of base-pairs of DNA in the human genome has been known since the 1960s, the estimated number of genes has changed over time as definitions of genes, and methods of detecting them have been refined. Initial theoretical predictions of the number of human genes were as high as 2,000,000. Early experimental measures indicated there to be 50,000–100,000 transcribed genes (expressed sequence tags). Subsequently, the sequencing in the Human Genome Project indicated that many of these transcripts were alternative variants of the same genes, and the total number of protein-coding genes was revised down to ~20,000 with 13 genes encoded on the mitochondrial genome. Of the human genome, only 1–2% consists of protein-coding genes, with the remainder being 'noncoding' DNA such as introns, retrotransposons, and noncoding RNAs.


Essential genes are the set of genes thought to be critical for an organism's survival. This definition assumes the abundant availability of all relevant nutrients and the absence of environmental stress. Only a small portion of an organism's genes are essential. In bacteria, an estimated 250–400 genes are essential for Escherichia coli and Bacillus subtilis, which is less than 10% of their genes. Half of these genes are orthologs in both organisms and are largely involved in protein synthesis. In the budding yeast Saccharomyces cerevisiae the number of essential genes is slightly higher, at 1000 genes (~20% of their genes). Although the number is more difficult to measure in higher eukaryotes, mice and humans are estimated to have around 2000 essential genes (~10% of their genes).


Housekeeping genes are critical for carrying out basic cell functions and so are expressed at a relatively constant level (constitutively). Since their expression is constant, housekeeping genes are used as experimental controls when analysing gene expression. Not all essential genes are housekeeping genes since some essential genes are developmentally regulated or expressed at certain times during the organism's life cycle.


Gene nomenclature has been established by the HUGO Gene Nomenclature Committee (HGNC) for each known human gene in the form of an approved gene name and symbol (short-form abbreviation), which can be accessed through a database maintained by HGNC. Symbols are chosen to be unique, and each gene has only one symbol (although approved symbols sometimes change). Symbols are preferably kept consistent with other members of a gene family and with homologs in other species, particularly the mouse due to its role as a common model organism.


Genetic engineering is the modification of an organism's genome through biotechnology. Since the 1970s, a variety of techniques have been developed to specifically add, remove and edit genes in an organism. Recently developed genome engineering techniques use engineered nuclease enzymes to create targeted DNA repair in a chromosome to either disrupt or edit a gene when the break is repaired. The related term synthetic biology is sometimes used to refer to extensive genetic engineering of an organism.


Genetic engineering is now a routine research tool with model organisms. For example, genes are easily added to bacteria and lineages of knockout mice with a specific gene's function disrupted are used to investigate that gene's function. Many organisms have been genetically modified for applications in agriculture, industrial biotechnology, and medicine.


For multicellular organisms, typically the embryo is engineered which grows into the adult genetically modified organism. However, the genomes of cells in an adult organism can be edited using gene therapy techniques to treat genetic diseases.


Guinea-Bissau (i/ˈɡɪni bɪˈsaʊ/, GI-nee-bi-SOW), officially the Republic of Guinea-Bissau (Portuguese: República da Guiné-Bissau, pronounced: [ʁeˈpublikɐ dɐ ɡiˈnɛ biˈsaw]), is a country in West Africa. It covers 36,125 square kilometres (13,948 sq mi) with an estimated population of 1,704,000.


Guinea-Bissau was once part of the kingdom of Gabu, as well as part of the Mali Empire. Parts of this kingdom persisted until the 18th century, while a few others were under some rule by the Portuguese Empire since the 16th century. In the 19th century, it was colonized as Portuguese Guinea. Upon independence, declared in 1973 and recognised in 1974, the name of its capital, Bissau, was added to the country's name to prevent confusion with Guinea (formerly French Guinea). Guinea-Bissau has a history of political instability since independence, and no elected president has successfully served a full five-year term.


Only 14% of the population speaks Portuguese, established as the official language in the colonial period. Almost half the population (44%) speaks Crioulo, a Portuguese-based creole language, and the remainder speak a variety of native African languages. The main religions are African traditional religions and Islam; there is a Christian (mostly Roman Catholic) minority. The country's per-capita gross domestic product is one of the lowest in the world.


Guinea-Bissau is a member of the United Nations, African Union, Economic Community of West African States, Organisation of Islamic Cooperation, the Latin Union, Community of Portuguese Language Countries, La Francophonie and the South Atlantic Peace and Cooperation Zone.


Guinea-Bissau was once part of the kingdom of Gabu, part of the Mali Empire; parts of this kingdom persisted until the 18th century. Other parts of the territory in the current country were considered by the Portuguese as part of their empire. Portuguese Guinea was known as the Slave Coast, as it was a major area for the exportation of African slaves by Europeans to the western hemisphere. Previously slaves had been traded by Arabs north to the northern part of Africa and into the Middle East.


Early reports of Europeans reaching this area include those of the Venetian Alvise Cadamosto's voyage of 1455, the 1479–1480 voyage by Flemish-French trader Eustache de la Fosse, and Diogo Cão. In the 1480s this Portuguese explorer reached the Congo River and the lands of Bakongo, setting up the foundations of modern Angola, some 4200 km down the African coast from Guinea-Bissau.


Although the rivers and coast of this area were among the first places colonized by the Portuguese, who set up trading posts in the 16th century, they did not explore the interior until the 19th century. The local African rulers in Guinea, some of whom prospered greatly from the slave trade, controlled the inland trade and did not allow the Europeans into the interior. They kept them in the fortified coastal settlements where the trading took place. African communities that fought back against slave traders also distrusted European adventurers and would-be settlers. The Portuguese in Guinea were largely restricted to the port of Bissau and Cacheu. A small number of European settlers established isolated farms along Bissau's inland rivers.


For a brief period in the 1790s, the British tried to establish a rival foothold on an offshore island, at Bolama. But by the 19th century the Portuguese were sufficiently secure in Bissau to regard the neighbouring coastline as their own special territory, also up north in part of present South Senegal.


An armed rebellion beginning in 1956 by the African Party for the Independence of Guinea and Cape Verde (PAIGC) under the leadership of Amílcar Cabral gradually consolidated its hold on then Portuguese Guinea. Unlike guerrilla movements in other Portuguese colonies, the PAIGC rapidly extended its military control over large portions of the territory, aided by the jungle-like terrain, its easily reached borderlines with neighbouring allies, and large quantities of arms from Cuba, China, the Soviet Union, and left-leaning African countries. Cuba also agreed to supply artillery experts, doctors, and technicians. The PAIGC even managed to acquire a significant anti-aircraft capability in order to defend itself against aerial attack. By 1973, the PAIGC was in control of many parts of Guinea, although the movement suffered a setback in January 1973 when Cabral was assassinated.


Independence was unilaterally declared on 24 September 1973. Recognition became universal following the 25 April 1974 socialist-inspired military coup in Portugal, which overthrew Lisbon's Estado Novo regime.


Luís Cabral, brother of Amílcar and co-founder of PAIGC, was appointed the first President of Guinea-Bissau. Following independence, the PAIGC killed thousands of local Guinean soldiers who had fought along with the Portuguese Army against guerrillas. Some escaped to settle in Portugal or other African nations. One of the massacres occurred in the town of Bissorã. In 1980 the PAIGC acknowledged in its newspaper Nó Pintcha (dated 29 November 1980) that many Gueinean soldiers had been executed and buried in unmarked collective graves in the woods of Cumerá, Portogole, and Mansabá.


The country was controlled by a revolutionary council until 1984. The first multi-party elections were held in 1994. An army uprising in May 1998 led to the Guinea-Bissau Civil War and the president's ousting in June 1999. Elections were held again in 2000, and Kumba Ialá was elected president.


In September 2003, a military coup was conducted. The military arrested Ialá on the charge of being "unable to solve the problems". After being delayed several times, legislative elections were held in March 2004. A mutiny of military factions in October 2004 resulted in the death of the head of the armed forces and caused widespread unrest.


In June 2005, presidential elections were held for the first time since the coup that deposed Ialá. Ialá returned as the candidate for the PRS, claiming to be the legitimate president of the country, but the election was won by former president João Bernardo Vieira, deposed in the 1999 coup. Vieira beat Malam Bacai Sanhá in a runoff election. Sanhá initially refused to concede, claiming that tampering and electoral fraud occurred in two constituencies including the capital, Bissau.


Despite reports of arms entering the country prior to the election and some "disturbances during campaigning," including attacks on government offices by unidentified gunmen, foreign election monitors described the 2005 election overall as "calm and organized".


Three years later, PAIGC won a strong parliamentary majority, with 67 of 100 seats, in the parliamentary election held in November 2008. In November 2008, President Vieira's official residence was attacked by members of the armed forces, killing a guard but leaving the president unharmed.


On 2 March 2009, however, Vieira was assassinated by what preliminary reports indicated to be a group of soldiers avenging the death of the head of joint chiefs of staff, General Batista Tagme Na Wai. Tagme died in an explosion on Sunday, 1 March 2009, target of an assassination. Military leaders in the country pledged to respect the constitutional order of succession. National Assembly Speaker Raimundo Pereira was appointed as an interim president until a nationwide election on 28 June 2009. It was won by Malam Bacai Sanhá.


On the evening of 12 April 2012, members of the country's military staged a coup d'état and arrested the interim president and a leading presidential candidate. Former vice chief of staff, General Mamadu Ture Kuruma, assumed control of the country in the transitional period and started negotiations with opposition parties.


Guinea-Bissau is a republic. In the past, the government had been highly centralized. Multi-party governance was not established until mid-1991. The president is the head of state and the prime minister is the head of government. Since 1974, no president has successfully served a full five-year term.


At the legislative level, a unicameral Assembleia Nacional Popular (National People's Assembly) is made up of 100 members. They are popularly elected from multi-member constituencies to serve a four-year term. The judicial system is headed by a Tribunal Supremo da Justiça (Supreme Court), made up of nine justices appointed by the president; they serve at the pleasure of the president.


João Bernardo "Nino" Vieira was elected in 2005 as President of Guinea-Bissau as an independent, being declared winner of the second round by the CNE (Comité Nacional de Eleições). Vieira returned to power in 2005 six years after being ousted from office during a civil war. Previously, he held power for 19 years after taking power in 1980 in a bloodless coup. In that action, he toppled the government of Luís Cabral.


He was killed on 2 March 2009, possibly by soldiers in retaliation for the assassination of General Batista Tagme Na Waie, the head of the joint chiefs of staff, killed in an explosion. Vieira's death did not trigger widespread violence, but there were signs of turmoil in the country, according to the advocacy group Swisspeace. Malam Bacai Sanhá was elected after a transition. In the 2009 election to replace the assassinated Vieira, Sanhá was the presidential candidate of the PAIGC while Kumba Ialá was the presidential candidate of the PRS.


In 2012, President Rachide Sambu-balde Malam Bacai Sanhá died. He belonged to PAIGC (African Party for the Independence of Guinea and Cape Verde), one of the two major political parties in Guinea-Bissau, along with the PRS (Party for Social Renewal). There are more than 20 minor parties.


Guinea-Bissau is divided into eight regions (regiões) and one autonomous sector (sector autónomo). These, in turn, are subdivided into 37 Sectors. The regions are:


Guinea-Bissau is bordered by Senegal to the north and Guinea to the south and east, with the Atlantic Ocean to its west. It lies mostly between latitudes 11° and 13°N (a small area is south of 11°), and longitudes 13° and 17°W.


At 36,125 square kilometres (13,948 sq mi), the country is larger in size than Taiwan or Belgium. It lies at a low altitude; its highest point is 300 metres (984 ft). The terrain of is mostly low coastal plain with swamps of Guinean mangroves rising to Guinean forest-savanna mosaic in the east. Its monsoon-like rainy season alternates with periods of hot, dry harmattan winds blowing from the Sahara. The Bijagos Archipelago lies off of the mainland.


Guinea-Bissau is warm all year around and there is little temperature fluctuation; it averages 26.3 °C (79.3 °F). The average rainfall for Bissau is 2,024 millimetres (79.7 in) although this is almost entirely accounted for during the rainy season which falls between June and September/October. From December through April, the country experiences drought.


Guinea-Bissau's GDP per capita is one of the lowest in the world, and its Human Development Index is one of the lowest on earth. More than two-thirds of the population lives below the poverty line. The economy depends mainly on agriculture; fish, cashew nuts and ground nuts are its major exports.


A long period of political instability has resulted in depressed economic activity, deteriorating social conditions, and increased macroeconomic imbalances. It takes longer on average to register a new business in Guinea-Bissau (233 days or about 33 weeks) than in any other country in the world except Suriname. [The Economist, Pocket World in Figures, 2008 Edition, London: Profile Books]


Guinea-Bissau has started to show some economic advances after a pact of stability was signed by the main political parties of the country, leading to an IMF-backed structural reform program. The key challenges for the country in the period ahead are to achieve fiscal discipline, rebuild public administration, improve the economic climate for private investment, and promote economic diversification. After the country became independent from Portugal in 1974 due to the Portuguese Colonial War and the Carnation Revolution, the rapid exodus of the Portuguese civilian, military, and political authorities resulted in considerable damage to the country's economic infrastructure, social order, and standard of living.


After several years of economic downturn and political instability, in 1997, Guinea-Bissau entered the CFA franc monetary system, bringing about some internal monetary stability. The civil war that took place in 1998 and 1999, and a military coup in September 2003 again disrupted economic activity, leaving a substantial part of the economic and social infrastructure in ruins and intensifying the already widespread poverty. Following the parliamentary elections in March 2004 and presidential elections in July 2005, the country is trying to recover from the long period of instability, despite a still-fragile political situation.


Beginning around 2005, drug traffickers based in Latin America began to use Guinea-Bissau, along with several neighboring West African nations, as a transshipment point to Europe for cocaine. The nation was described by a United Nations official as being at risk for becoming a "narco-state". The government and the military have done little to stop drug trafficking, which increased after the 2012 coup d'état.


According to the 2010 revison of the UN World Population Prospects, Guinea-Bissau's population was 1,515,000 in 2010, compared to 518,000 in 1950. The proportion of the population below the age of 15 in 2010 was 41.3%, 55.4% were aged between 15 and 65 years of age, while 3.3% were aged 65 years or older.


Portuguese natives comprise a very small percentage of Guinea-Bissauans. After Guinea-Bissau gained independence, most of the Portuguese nationals left the country. The country has a tiny Chinese population. These include traders and merchants of mixed Portuguese and Chinese ancestry from Macau, a former Asian Portuguese colony.


14% of the population speaks the official language Portuguese, the language of government and national communication during centuries of colonial rule. 44% speak Kriol, a Portuguese-based creole language, which is effectively a national language of communication among groups. The remainder speak a variety of native African languages unique to ethnicities.


Most Portuguese and Mestiços speak one of the African languages and Kriol as second languages. French is also taught in schools because Guinea-Bissau is surrounded by French-speaking nations. Guinea-Bissau is a full member of the Francophonie.


Throughout the 20th century, most Bissau-Guineans practiced some form of Animism. In the early 21st century, many have adopted Islam, which is now practiced by 50% of the country's population. Most of Guinea-Bissau's Muslims are of the Sunni denomination with approximately 2% belonging to the Ahmadiyya sect.


Approximately 10% of the country's population belong to the Christian community, and 40% continue to hold Indigenous beliefs. These statistics can be misleading, however, as many residents practice syncretic forms of Islamic and Christian faiths, combining their practices with traditional African beliefs.


The prevalence of HIV-infection among the adult population is 1.8%. Only 20% of infected pregnant women receive anti retroviral coverage to prevent transmission to newborns.


Malaria kills more residents; 9% of the population have reported infection, It causes three times as many deaths as AIDS. In 2008, fewer than half of children younger than five slept under antimalaria nets or had access to antimalarial drugs.


Despite lowering rates in surrounding countries, cholera rates were reported in November 2012 to be on the rise, with 1,500 cases reported and nine deaths. A 2008 cholera epidemic in Guinea-Bissau affected 14,222 people and killed 225.


The 2010 maternal mortality rate per 100,000 births for Guinea Bissau was 1000. This compares with 804.3 in 2008 and 966 in 1990. The under 5 mortality rate, per 1,000 births, was 195 and the neonatal mortality as a percentage of under 5's mortality was 24. The number of midwives per 1,000 live births was 3; one out of eighteen pregnant women die as a result of pregnancy. According to a 2013 UNICEF report, 50% of women in Guinea Bissau had undergone female genital mutilation. In 2010, Guinea Bissau had the 7th highest maternal mortality rate in the world.


Education is compulsory from the age of 7 to 13. The enrollment of boys is higher than that of girls. In 1998, the gross primary enrollment rate was 53.5%, with higher enrollment ratio for males (67.7%) compared to females (40%).


Guinea-Bissau has several secondary schools (general as well as technical) and a number of universities, to which an institutionally autonomous Faculty of Law as well as a Faculty of Medicine have been added.


The music of Guinea-Bissau is usually associated with the polyrhythmic gumbe genre, the country's primary musical export. However, civil unrest and other factors have combined over the years to keep gumbe, and other genres, out of mainstream audiences, even in generally syncretist African countries.


The calabash is the primary musical instrument of Guinea-Bissau, and is used in extremely swift and rhythmically complex dance music. Lyrics are almost always in Guinea-Bissau Creole, a Portuguese-based creole language, and are often humorous and topical, revolving around current events and controversies, especially AIDS.


The word gumbe is sometimes used generically, to refer to any music of the country, although it most specifically refers to a unique style that fuses about ten of the country's folk music traditions. Tina and tinga are other popular genres, while extent folk traditions include ceremonial music used in funerals, initiations and other rituals, as well as Balanta brosca and kussundé, Mandinga djambadon, and the kundere sound of the Bissagos Islands.


Rice is a staple in the diet of residents near the coast and millet a staple in the interior. Fish, shellfish, fruits and vegetables are commonly eaten along with cereal grains, milk, curd and whey. The Portuguese encouraged peanut production. Vigna subterranea (Bambara groundnut) and Macrotyloma geocarpum (Hausa groundnut) are also grown. Black-eyed peas are also part of the diet. Palm oil is harvested.


Common dishes include soups and stews. Common ingredients include yams, sweet potato, cassava, onion, tomato and plantain. Spices, peppers and chilis are used in cooking, including Aframomum melegueta seeds (Guinea pepper).


Flora Gomes is an internationally renowned film director; his most famous film is Nha Fala (English: My Voice). Gomes's Mortu Nega (Death Denied) (1988) was the first fiction film and the second feature film ever made in Guinea-Bissau. (The first feature film was N’tturudu, by director Umban u’Kest in 1987.) At FESPACO 1989, Mortu Nega won the prestigious Oumarou Ganda Prize. Mortu Nega is in Creole with English subtitles. In 1992, Gomes directed Udju Azul di Yonta, which was screened in the Un Certain Regard section at the 1992 Cannes Film Festival. Gomes has also served on the boards of many Africa-centric film festivals.


This article covers numbered east-west streets in Manhattan, New York City. Major streets have their own linked articles; minor streets are discussed here. The streets do not run exactly east–west, because the grid plan is aligned with the Hudson River rather than with the cardinal directions. "West" is approximately 29 degrees north of true west.


The numbered streets carry crosstown traffic. In general, even-numbered streets are one-way eastbound and odd-numbered streets are one-way west. Several exceptions reverse this. Most wider streets carry two-way traffic, as do a few of the narrow ones.


Streets' names change from West to East (for instance, East 10th Street to West 10th Street) at Broadway below 8th Street, and at Fifth Avenue from 8th Street and above.


Although the numbered streets begin just north of East Houston Street in the East Village, they generally do not extend west into Greenwich Village, which already had streets when the grid plan was laid out by the Commissioners' Plan of 1811. Streets that do continue farther west change direction before reaching the Hudson River. The grid covers the length of the island from 14th Street north.


220th Street is the highest numbered street on Manhattan Island. Marble Hill is also within the borough of Manhattan, so the highest street number in the borough is 228th Street. However, the numbering continues in the Bronx up to 263rd Street. The lowest number is East First Street—which runs in Alphabet City near East Houston Street—as well as First Place in Battery Park City.


East 1st Street begins just North of East Houston Street at Avenue A and continues to Bowery. Peretz Square, a small triangular sliver park where Houston Street, First Street and First Avenue meet marks the spot where the grid takes hold.


East 2nd Street begins just North of East Houston Street at Avenue C and also continues to Bowery. The East end of East 3rd, 4th, 5th, and 7th Streets is Avenue D, with East 6th Street continuing further Eastward and connecting to FDR Drive.


The west end of these streets is Bowery and Third Avenue, except for 3rd Street (formerly Amity Place; to Sixth Avenue) and 4th Street (to 13th Street), which extend west and north, respectively, into Greenwich Village. Great Jones Street connects East 3rd to West 3rd.


East 5th Street goes west to Cooper Square, but is interrupted between Avenues B and C by The Earth School, Public School 364, and between First Avenue and Avenue A by the Village View Apartments.


8th and 9th Streets run parallel to each other, beginning at Avenue D, interrupted by Tompkins Square Park at Avenue B, resuming at Avenue A and continuing to Sixth Avenue. West 8th Street is an important local shopping street. 8th Street between Avenue A and Third Avenue is called St Mark's Place, but it is counted in the length below.


10th Street (40°44′03″N 74°00′11″W / 40.7342580°N 74.0029670°W / 40.7342580; -74.0029670) begins at the FDR Drive and Avenue C. West of Sixth Avenue, it turns southward about 40 degrees to join the Greenwich Village street grid and continue to West Street on the Hudson River. Because West 4th Street turns northward at Sixth Avenue, it intersects 10th, 11th and 12th and 13th Streets in the West Village. The M8 bus operates on 10th Street in both directions between Avenue D and Avenue A, and eastbound between West Street and Sixth Avenue. 10th Street has an eastbound bike lane from West Street to the East River. In 2009, the two-way section of 10th Street between Avenue A and the East River had bicycle markings and sharrows installed, but it still has no dedicated bike lane. West 10th Street was previously named Amos Street for Richard Amos. The end of West 10th Street toward the Hudson River was once the home of Newgate Prison, New York City's first prison and the United States' second.


11th Street is in two parts. It is interrupted by the block containing Grace Church between Broadway and Fourth Avenue. East 11th streets runs from Fourth Avenue to Avenue C and runs past Webster Hall. West 11th Street runs from Broadway to West Street. 11th Street and 6th Avenue was the location of the Old Grapevine tavern from the 1700s to its demolition in the early 20th century.


13th Street is in three parts. The first is a dead end from Avenue C. The second starts at a dead end, just before Avenue B, and runs to Greenwich Avenue, and the third part is from Eighth Avenue to Tenth Avenue.


14th Street is a main numbered street in Manhattan. It begins at Avenue C and ends at West Street. Its length is 3.4 km (2.1 mi). It has six subway stations:


15th Street starts at FDR Drive, and 16th Street starts at a dead end half way between FDR Drive and Avenue C. They are both stopped at Avenue C and continue from First Avenue to West Street, stopped again at Union Square, and 16th Street also pauses at Stuyvesant Square.


On 17th Street (40°44′08″N 73°59′12″W / 40.735532°N 73.986575°W / 40.735532; -73.986575), traffic runs one way along the street, from east to west excepting the stretch between Broadway and Park Avenue South, where traffic runs in both directions. It forms the northern borders of both Union Square (between Broadway and Park Avenue South) and Stuyvesant Square. Composer Antonín Dvořák's New York home was located at 327 East 17th Street, near Perlman Place. The house was razed by Beth Israel Medical Center after it received approval of a 1991 application to demolish the house and replace it with an AIDS hospice. Time Magazine was started at 141 East 17th Street.


18th Street has a local subway station at the crossing with Seventh Avenue, served by the 1 2 trains on the IRT Broadway – Seventh Avenue Line. There used to be an 18th Street station on the IRT Lexington Avenue Line at the crossing with Park Avenue South.


20th Street starts at Avenue C, and 21st and 22nd Streets begin at First Avenue. They all end at Eleventh Avenue. Travel on the last block of the 20th, 21st and 22nd Streets, between Tenth and Eleventh Avenues, is in the opposite direction than it is on the rest of the respective street. 20th Street is very wide from the Avenue C to First Avenue.


Between Second and Third Avenues, 21st Street is alternatively known as Police Officer Anthony Sanchez Way. Along the northern perimeter of Gramercy Park, between Gramercy Park East and Gramercy Park West, 21st Street is known as Gramercy Park North.


23rd Street is another main numbered street in Manhattan. It begins at FDR Drive and ends at Eleventh Avenue. Its length is 3.1 km/1.9m. It has two-way travel. On 23rd Street there are five local subway stations:


24th Street is in two parts. 24th Street starts at First Avenue and it ends at Madison Avenue, because of Madison Square Park. 25th Street, which is in three parts, starts at FDR Drive, is a pedestrian plaza between Third Avenue and Lexington Avenue, and ends at Madison. Then West 24th and 25th Streets continue from Fifth Avenue to Eleventh Avenue (25th) or Twelfth Avenue (24th).


27th Street is a one-way street runs from Second Avenue to the West Side Highway with an interruption between Eighth Avenue and Tenth Avenue. It is most noted for its strip between Tenth and Eleventh Avenues, known as Club Row because it features numerous nightclubs and lounges.


In recent years, the nightclubs on West 27th Street have succumbed to stiff competition from Manhattan's Meatpacking District about fifteen blocks south, and other venues in downtown Manhattan.


Heading east, 27th Street passes through Chelsea Park between Tenth and Ninth Avenues, with the Fashion Institute of Technology (FIT) on the corner of Eighth. On Madison Avenue between 26th and 27th streets, on the site of the old Madison Square Garden, is the New York Life Building, built in 1928 and designed by Cass Gilbert, with a square tower topped by a striking gilded pyramid. Twenty-Seventh Street passes one block north of Madison Square Park and culminates at Bellevue Hospital Center on First Avenue.


31st Street begins on the West Side at the West Side Yard, while 32nd Street, which includes a segment officially known as Korea Way between Fifth Avenue and Broadway in Manhattan's Koreatown, begins at the entrance to Penn Station and Madison Square Garden. On the East Side, both streets end at Second Avenue at Kips Bay Towers and NYU Medical Center which occupy the area between 30th and 34th Streets. The Catholic church of St. Francis of Assisi is situated at 135–139 West 31st Street. At 210 West is the Capuchin Monastery of St. John the Baptist, part of St. John the Baptist Church on 30th Street. At the corner of Broadway and West 31st Street is the Grand Hotel. The former Hotel Pierrepont was located at 43 West 32nd Street, The Continental NYC tower is at the corner of Sixth Avenue and 32nd Street. 29 East 32nd Street was the location of the first building owned by the Grolier Club between 1890 and 1917.


35th Street runs from FDR Drive to Eleventh Avenue. Notable locations include East River Ferry, LaptopMD headquarters, Mercy College Manhattan Campus, and Jacob K. Javits Convention Center.


A section of East 58th Street 40°45′40.3″N 73°57′56.9″W / 40.761194°N 73.965806°W / 40.761194; -73.965806 between Lexington and Second Avenues is known as Designers' Way and features a number of high end interior design and decoration establishments, including


90th Street is split into two segments. The first segment, West 90th Street begins at Riverside Drive and ends at Central Park West or West Drive, when it is open, in Central Park on the Upper West Side. The second segment of East 90th Street begins at East Drive, at Engineers Gate of Central Park. When East Drive is closed, East 90th Street begins at Fifth Avenue on the Upper East Side and curves to the right at the FDR Drive becoming East End Avenue. Our Lady of Good Counsel Church, is located on East 90th Street between Third Avenue and Second Avenue, across the street from Ruppert Towers (1601 and 1619 Third Avenue) and Ruppert Park. Asphalt Green, which is located on East 90th Street between York Avenue and East End Avenue.


112th Street starts in Morningside Heights and runs from Riverside Drive to Amsterdam Avenue, where it meets the steps of the Cathedral of Saint John the Divine. The street resumes at the eastern edge of Morningside Park and extends through Harlem before ending at First Avenue adjacent Thomas Jefferson Park in East Harlem. Notable locations include:


114th Street marks the southern boundary of Columbia University’s Morningside Heights Campus and is the location of Butler Library, which is the University’s largest.


Above 114th Street between Amsterdam Avenue and Morningside Drive, there is a private indoor pedestrian bridge connecting two buildings on the campus of St. Luke's–Roosevelt Hospital Center.


40°48′27″N 73°57′18″W / 40.8076°N 73.9549°W / 40.8076; -73.9549 120th Street traverses the neighborhoods of Morningside Heights, Harlem, and Spanish Harlem. It begins on Riverside Drive at the Interchurch Center. It then runs east between the campuses of Barnard College and the Union Theological Seminary, then crosses Broadway and runs between the campuses of Columbia University and Teacher's College. The street is interrupted by Morningside Park. It then continues east, eventually running along the southern edge of Marcus Garvey Park, passing by 58 West, the former residence of Maya Angelou. It then continues through Spanish Harlem; when it crosses Pleasant Avenue it becomes a two‑way street and continues nearly to the East River, where for automobiles, it turns north and becomes Paladino Avenue, and for pedestrians, continues as a bridge across FDR Drive.


40°48′32″N 73°57′14″W / 40.8088°N 73.9540°W / 40.8088; -73.9540 122nd Street is divided into three noncontiguous segments, E 122nd Street, W 122nd Street, and W 122nd Street Seminary Row, by Marcus Garvey Memorial Park and Morningside Park.


E 122nd Street runs four blocks (2,250 feet (690 m)) west from the intersection of Second Avenue and terminates at the intersection of Madison Avenue at Marcus Garvey Memorial Park. This segment runs in East Harlem and crosses portions of Third Avenue, Lexington, and Park (Fourth Avenue).


W 122nd Street runs six blocks (3,280 feet (1,000 m)) west from the intersection of Mount Morris Park West at Marcus Garvey Memorial Park and terminates at the intersection of Morningside Avenue at Morningside Park. This segment runs in the Mount Morris Historical District and crosses portions of Lenox Avenue (Sixth Avenue), Seventh Avenue, Frederick Douglass Boulevard (Eighth Avenue), and Manhattan Avenue.


W 122nd Street Seminary Row runs three blocks (1,500 feet (460 m)) west from the intersection of Amsterdam Avenue (Tenth Avenue) and terminates at the intersection of Riverside Drive. East of Amsterdam, Seminary Row bends south along Morningside Park and is resigned as Morningside Drive (Ninth Avenue). Seminary row runs in Morningside Heights, the district surrounding Columbia University, and crosses portions of Broadway and Claremont Avenue.


Seminary Row is named for the Union Theological Seminary and the Jewish Theological Seminary which it touches. Seminary Row also runs by the Manhattan School of Music, Riverside Church, Sakura Park, Grant's Tomb, and Morningside Park.


122nd Street is mentioned in the movie Taxi Driver by main character Travis Bickle as the location where a fellow cab driver is assaulted with a knife. The street and the surrounding neighborhood of Harlem is then referred to as "Mau Mau Land" by another character named Wizard, slang indicating it is a majority black area.


40°48′47″N 73°57′27″W / 40.813°N 73.9575°W / 40.813; -73.9575 La Salle Street is a street in West Harlem that runs just two blocks between Amsterdam Avenue and Claremont Avenue. West of Convent Avenue, 125th Street was re-routed onto the old Manhattan Avenue. The original 125th Street west of Convent Avenue was swallowed up to make the super-blocks where the low income housing projects now exist. La Salle Street is the only vestige of the original routing.


40°48′52″N 73°56′53″W / 40.814583°N 73.947944°W / 40.814583; -73.947944 132nd Street runs east-west above Central Park and is located in Harlem just south of Hamilton Heights. The main portion of 132nd Street runs eastbound from Frederick Douglass Boulevard to northern end of Park Avenue where there is a southbound exit from/entrance to the Harlem River Drive. After an interruption from St. Nicholas Park and City College, there is another small stretch of West 132nd Street between Broadway and Twelfth Avenue


The 132nd Street Community Garden is located on 132nd Street between Adam Clayton Powell Jr. Boulevard and Malcolm X Boulevard. In 1997, the lot received a garden makeover; the Borough President's office funded the installation of a $100,000 water distribution system that keeps the wide variety of trees green. The garden also holds a goldfish pond and several benches. The spirit of the neighborhood lives in gardens like this one, planted and tended by local residents.


The Manhattanville Bus Depot (formerly known as the 132nd Street Bus Depot) is located on West 132nd and 133rd Street between Broadway and Riverside Drive in the Manhattanville neighborhood.


155th Street is a major crosstown street considered to form the boundary between Harlem and Washington Heights. It is the northernmost of the 155 crosstown streets mapped out in the Commissioner's Plan of 1811 that established the numbered street grid in Manhattan.


155th Street starts on the West Side at Riverside Drive, crossing Broadway, Amsterdam Avenue and St. Nicholas Avenue. At St. Nicholas Place, the terrain drops off steeply, and 155th Street is carried on a 1,600-foot (490 m) long viaduct, a City Landmark constructed in 1893, that slopes down towards the Harlem River, continuing onto the Macombs Dam Bridge, crossing over (but not intersecting with) the Harlem River Drive. A separate, unconnected section of 155th Street runs under the viaduct, connecting Bradhurst Avenue and the Harlem River Drive.


181st Street is a major thoroughfare running through the Washington Heights neighborhood. It runs from the Washington Bridge in the east, to the Henry Hudson Parkway in the west, near the George Washington Bridge and the Hudson River. The west end is called Plaza Lafayette.


West of Fort Washington Avenue, 181st Street is largely residential, bordering Hudson Heights and having a few shops to serve the local residents. East of Fort Washington Avenue, the street becomes increasingly commercial, becoming dominated entirely by retail stores where the street reaches Broadway and continues as such until reaching the Harlem River. It is the area's major shopping district.


181st Street is served by two New York City Subway lines; there is a 181st Street station at Fort Washington Avenue on the IND Eighth Avenue Line (A trains) and a 181st Street station at St. Nicholas Avenue on the IRT Broadway – Seventh Avenue Line (1 trains). The stations are about 500 metres (550 yd) from each other and are not connected. The George Washington Bridge Bus Terminal is a couple of blocks south on Fort Washington Avenue. 181st Street is also the last south/west exit in New York on the Trans-Manhattan Expressway (I-95), just before crossing the George Washington Bridge to New Jersey.


187th Street crosses Washington Heights and running from Laurel Hill Terrace in the east to Chittenden Avenue in the west near the George Washington Bridge and Hudson River. The street is interrupted by a long set of stairs east of Fort Washington Avenue leading to the Broadway valley. West of there, it is mostly lined with store fronts and serves as a main shopping district for the Hudson Heights neighborhood.


187th Street intersects with, from East to West, Laurel Hill Terrace, Amsterdam Avenue, Audubon Avenue, St. Nicholas Avenue, Wadsworth Avenue, Broadway, Bennett Avenue, Overlook Terrace, Fort Washington Avenue, Pinehurst Avenue, Cabrini Boulevard and Chittenden Avenue.


The many institutions on 187th Street include Mount Sinai Jewish Center, the Dombrov Shtiebel, and the uptown campus of Yeshiva University. The local public elementary school P.S. 187 is located on Cabrini Boulevard, just north of the eponymous 187th Street


The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. Only a few invertebrates such as sponges, jellyfish, adult sea squirts and starfish do not have a brain; diffuse or localised nerve nets are present instead. The brain is located in the head, usually close to the primary sensory organs for such senses as vision, hearing, balance, taste, and smell. The brain is the most complex organ in a vertebrate's body. In a typical human, the cerebral cortex (the largest part) is estimated to contain 15–33 billion neurons, each connected by synapses to several thousand other neurons. These neurons communicate with one another by means of long protoplasmic fibers called axons, which carry trains of signal pulses called action potentials to distant parts of the brain or body targeting specific recipient cells.


Physiologically, the function of the brain is to exert centralized control over the other organs of the body. The brain acts on the rest of the body both by generating patterns of muscle activity and by driving the secretion of chemicals called hormones. This centralized control allows rapid and coordinated responses to changes in the environment. Some basic types of responsiveness such as reflexes can be mediated by the spinal cord or peripheral ganglia, but sophisticated purposeful control of behavior based on complex sensory input requires the information integrating capabilities of a centralized brain.


The operations of individual brain cells are now understood in considerable detail but the way they cooperate in ensembles of millions is yet to be solved. Recent models in modern neuroscience treat the brain as a biological computer, very different in mechanism from an electronic computer, but similar in the sense that it acquires information from the surrounding world, stores it, and processes it in a variety of ways, analogous to the central processing unit (CPU) in a computer.


This article compares the properties of brains across the entire range of animal species, with the greatest attention to vertebrates. It deals with the human brain insofar as it shares the properties of other brains. The ways in which the human brain differs from other brains are covered in the human brain article. Several topics that might be covered here are instead covered there because much more can be said about them in a human context. The most important is brain disease and the effects of brain damage, covered in the human brain article because the most common diseases of the human brain either do not show up in other species, or else manifest themselves in different ways.


The shape and size of the brain varies greatly in different species, and identifying common features is often difficult. Nevertheless, there are a number of principles of brain architecture that apply across a wide range of species. Some aspects of brain structure are common to almost the entire range of animal species; others distinguish "advanced" brains from more primitive ones, or distinguish vertebrates from invertebrates.


The simplest way to gain information about brain anatomy is by visual inspection, but many more sophisticated techniques have been developed. Brain tissue in its natural state is too soft to work with, but it can be hardened by immersion in alcohol or other fixatives, and then sliced apart for examination of the interior. Visually, the interior of the brain consists of areas of so-called grey matter, with a dark color, separated by areas of white matter, with a lighter color. Further information can be gained by staining slices of brain tissue with a variety of chemicals that bring out areas where specific types of molecules are present in high concentrations. It is also possible to examine the microstructure of brain tissue using a microscope, and to trace the pattern of connections from one brain area to another.


The brains of all species are composed primarily of two broad classes of cells: neurons and glial cells. Glial cells (also known as glia or neuroglia) come in several types, and perform a number of critical functions, including structural support, metabolic support, insulation, and guidance of development. Neurons, however, are usually considered the most important cells in the brain. The property that makes neurons unique is their ability to send signals to specific target cells over long distances. They send these signals by means of an axon, which is a thin protoplasmic fiber that extends from the cell body and projects, usually with numerous branches, to other areas, sometimes nearby, sometimes in distant parts of the brain or body. The length of an axon can be extraordinary: for example, if a pyramidal cell, (an excitatory neuron) of the cerebral cortex were magnified so that its cell body became the size of a human body, its axon, equally magnified, would become a cable a few centimeters in diameter, extending more than a kilometer. These axons transmit signals in the form of electrochemical pulses called action potentials, which last less than a thousandth of a second and travel along the axon at speeds of 1–100 meters per second. Some neurons emit action potentials constantly, at rates of 10–100 per second, usually in irregular patterns; other neurons are quiet most of the time, but occasionally emit a burst of action potentials.


Axons transmit signals to other neurons by means of specialized junctions called synapses. A single axon may make as many as several thousand synaptic connections with other cells. When an action potential, traveling along an axon, arrives at a synapse, it causes a chemical called a neurotransmitter to be released. The neurotransmitter binds to receptor molecules in the membrane of the target cell.


Synapses are the key functional elements of the brain. The essential function of the brain is cell-to-cell communication, and synapses are the points at which communication occurs. The human brain has been estimated to contain approximately 100 trillion synapses; even the brain of a fruit fly contains several million. The functions of these synapses are very diverse: some are excitatory (exciting the target cell); others are inhibitory; others work by activating second messenger systems that change the internal chemistry of their target cells in complex ways. A large number of synapses are dynamically modifiable; that is, they are capable of changing strength in a way that is controlled by the patterns of signals that pass through them. It is widely believed that activity-dependent modification of synapses is the brain's primary mechanism for learning and memory.


Most of the space in the brain is taken up by axons, which are often bundled together in what are called nerve fiber tracts. A myelinated axon is wrapped in a fatty insulating sheath of myelin, which serves to greatly increase the speed of signal propagation. (There are also unmyelinated axons). Myelin is white, making parts of the brain filled exclusively with nerve fibers appear as light-colored white matter, in contrast to the darker-colored grey matter that marks areas with high densities of neuron cell bodies.