2BKD , 2FMR , 2LA5 , 2QND , 4OVA , 4QVZ , 4QW2 , 5DE5 , 5DE8 , 5DEA
131-396: 2332 14265 ENSG00000102081 ENSMUSG00000000838 Q06787 P35922 NM_001185075 NM_001185076 NM_001185081 NM_001185082 NM_002024 NM_001290424 NM_008031 NM_001374719 NP_001172004 NP_001172005 NP_001172010 NP_001172011 NP_002015 n/a FMR1 ( Fragile X Messenger Ribonucleoprotein 1 ) is a human gene that codes for
262-415: A multi-layered network of cooperating, distinct, or even competing social groups – from families and peer groups to corporations and political states . As such, social interactions between humans have established a wide variety of values, social norms , languages , and traditions (collectively termed institutions ), each of which bolsters human society . Humans are also highly curious , with
393-417: A protein called fragile X messenger ribonucleoprotein , or FMRP. This protein, most commonly found in the brain, is essential for normal cognitive development and female reproductive function. Mutations of this gene can lead to fragile X syndrome , intellectual disability , premature ovarian failure , autism , Parkinson's disease , developmental delays and other cognitive deficits. The FMR1 premutation
524-668: A theory of mind . The human mind is capable of introspection , private thought , imagination , volition , and forming views on existence . This has allowed great technological advancements and complex tool development through complex reasoning and the transmission of knowledge to subsequent generations through language . Humans have had a dramatic effect on the environment . They are apex predators , being rarely preyed upon by other species. Human population growth , industrialization, land development, overconsumption and combustion of fossil fuels have led to environmental destruction and pollution that significantly contributes to
655-514: A base pair, leading to a change in one of the amino acids in the gene. These mutations disrupt the 3-dimensional shape of FMRP or prevent the protein from being synthesized, leading to the signs and symptoms of fragile X syndrome. A CGG sequence in the FMR1 gene that is repeated between 55 and 200 times is described as a premutation. Although most individuals with the premutation are intellectually normal, some of these individuals have mild versions of
786-419: A bulbous head (the spine head), and a thin neck that connects the head of the spine to the shaft of the dendrite. The dendrites of a single neuron can contain hundreds to thousands of spines. In addition to spines providing an anatomical substrate for memory storage and synaptic transmission, they may also serve to increase the number of possible contacts between neurons. It has also been suggested that changes in
917-478: A computationally simple version of the full Baer and Rinzel model. It was designed to be analytically tractable and have as few free parameters as possible while retaining those of greatest significance, such as spine neck resistance. The model drops the continuum approximation and instead uses a passive dendrite coupled to excitable spines at discrete points. Membrane dynamics in the spines are modelled using integrate and fire processes. The spike events are modelled in
1048-443: A consequence of better nutrition, healthcare, and living conditions. The average mass of an adult human is 59 kg (130 lb) for females and 77 kg (170 lb) for males. Like many other conditions, body weight and body type are influenced by both genetic susceptibility and environment and varies greatly among individuals. Humans have a far faster and more accurate throw than other animals. Humans are also among
1179-574: A correlation between age-related reductions in spine densities in the hippocampus and age-dependent declines in hippocampal learning and memory. Emerging evidence has also shown dendritic spine abnormalities in the pain processing regions of the spinal cord nociceptive system, including superficial and intermediate zones of the dorsal horn. Overall, the evidence suggests that dendritic spines are crucial for normal brain and spinal cord function. Alterations in spine morphology may not only influence synaptic plasticity and information processing but also have
1310-408: A discrete fashion with the wave form conventionally represented as a rectangular function. Calcium transients in spines are a key trigger for synaptic plasticity. NMDA receptors , which have a high permeability for calcium, only conduct ions if the membrane potential is sufficiently depolarized. The amount of calcium entering a spine during synaptic activity therefore depends on the depolarization of
1441-419: A few other places), saw the emergence of agriculture and permanent human settlement ; in turn, this led to the development of civilization and kickstarted a period of continuous (and ongoing) population growth and rapid technological change . Since then, a number of civilizations have risen and fallen, while a number of sociocultural and technological developments have resulted in significant changes to
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#17327723143001572-463: A great capacity for altering their habitats by means of technology, irrigation , urban planning , construction, deforestation and desertification . Human settlements continue to be vulnerable to natural disasters , especially those placed in hazardous locations and with low quality of construction. Grouping and deliberate habitat alteration is often done with the goals of providing protection, accumulating comforts or material wealth, expanding
1703-612: A higher body fat percentage. At puberty , humans develop secondary sex characteristics . Females are capable of pregnancy , usually between puberty, at around 12 years old, and menopause , around the age of 50. As omnivorous creatures, they are capable of consuming a wide variety of plant and animal material, and have used fire and other forms of heat to prepare and cook food since the time of Homo erectus . Humans can survive for up to eight weeks without food and several days without water . Humans are generally diurnal , sleeping on average seven to nine hours per day. Childbirth
1834-475: A human can lose personhood (such as by going into a persistent vegetative state ). Humans are apes ( superfamily Hominoidea ). The lineage of apes that eventually gave rise to humans first split from gibbons (family Hylobatidae) and orangutans (genus Pongo ), then gorillas (genus Gorilla ), and finally, chimpanzees and bonobos (genus Pan ). The last split, between the human and chimpanzee–bonobo lineages, took place around 8–4 million years ago, in
1965-547: A key role in many neurological diseases. Furthermore, even subtle changes in dendritic spine densities or sizes can affect neuronal network properties, which could lead to cognitive or mood alterations, impaired learning and memory, as well as pain hypersensitivity. Moreover, the findings suggest that maintaining spine health through therapies such as exercise, cognitive stimulation and lifestyle modifications may be helpful in preserving neuronal plasticity and improving neurological symptoms. Despite experimental findings that suggest
2096-574: A large group of target mRNAs; however the extent of FMRPs translational control is unknown. The protein has been shown to repress the translation of target mRNAs at synapses, including those encoding the cytoskeletal proteins Arc/Arg3.1 and MAP1B , and the CaM kinase II . In addition, FMRP binds PSD-95 and GluR1/2 mRNAs. Importantly, these FMRP-binding mRNAs play significant roles in neuronal plasticity. FMRP translational control has been shown to be regulated by mGluR signaling. mGluR stimulation may result in
2227-581: A more barrel-shaped chests in contrast to the funnel shape of other apes, an adaptation for bipedal respiration. Apart from bipedalism and brain size, humans differ from chimpanzees mostly in smelling , hearing and digesting proteins . While humans have a density of hair follicles comparable to other apes, it is predominantly vellus hair , most of which is so short and wispy as to be practically invisible. Humans have about 2 million sweat glands spread over their entire bodies, many more than chimpanzees, whose sweat glands are scarce and are mainly located on
2358-504: A much clearer picture of life at the time. Between the 8th and 6th century BCE, Europe entered the classical antiquity age, a period when ancient Greece and ancient Rome flourished. Around this time other civilizations also came to prominence. The Maya civilization started to build cities and create complex calendars . In Africa, the Kingdom of Aksum overtook the declining Kingdom of Kush and facilitated trade between India and
2489-410: A new cable theory for which the distribution of spines is treated as a continuum. In this representation, spine head voltage is the local spatial average of membrane potential in adjacent spines. The formulation maintains the feature that there is no direct electrical coupling between neighboring spines; voltage spread along dendrites is the only way for spines to interact. The SDS model was intended as
2620-414: A primarily actin cytoskeleton , they are dynamic, and the majority of spines change their shape within seconds to minutes because of the dynamicity of actin remodeling . Furthermore, spine number is very variable and spines come and go; in a matter of hours, 10-20% of spines can spontaneously appear or disappear on the pyramidal cells of the cerebral cortex, although the larger "mushroom"-shaped spines are
2751-451: A result, humans are a cosmopolitan species found in almost all regions of the world, including tropical rainforest , arid desert , extremely cold arctic regions , and heavily polluted cities; in comparison, most other species are confined to a few geographical areas by their limited adaptability. The human population is not, however, uniformly distributed on the Earth 's surface, because
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#17327723143002882-414: A result, this part of the FMR1 gene is methylated, which silences the gene (it is turned off and does not make any protein). Without adequate FMR1, severe learning disabilities or intellectual disabilities can develop, along with physical abnormalities seen in fragile X syndrome. Fewer than 1% of all cases of fragile X syndrome are caused by mutations that delete part or all of the FMR1 gene, or change
3013-509: A role for dendritic spine dynamics in mediating learning and memory, the degree of structural plasticity's importance remains debatable. For instance, studies estimate that only a small portion of spines formed during training actually contribute to lifelong learning. In addition, the formation of new spines may not significantly contribute to the connectivity of the brain, and spine formation may not bear as much of an influence on memory retention as other properties of structural plasticity, such as
3144-639: A similar species. Migrating out of Africa , they gradually replaced and interbred with local populations of archaic humans. Multiple hypotheses for the extinction of archaic human species such as Neanderthals include competition, violence , interbreeding with Homo sapiens , or inability to adapt to climate change . Humans began exhibiting behavioral modernity about 160,000–60,000 years ago. For most of their history, humans were nomadic hunter-gatherers. The Neolithic Revolution , which began in Southwest Asia around 13,000 years ago (and separately in
3275-515: A simple linear or branched progression but involved interbreeding between related species . Genomic research has shown that hybridization between substantially diverged lineages was common in human evolution. DNA evidence suggests that several genes of Neanderthal origin are present among all non sub-Saharan-African populations, and Neanderthals and other hominins, such as Denisovans , may have contributed up to 6% of their genome to present-day non sub-Saharan-African humans. Human evolution
3406-451: A successful labor increased significantly during the 20th century in wealthier countries with the advent of new medical technologies. In contrast, pregnancy and natural childbirth remain hazardous ordeals in developing regions of the world, with maternal death rates approximately 100 times greater than in developed countries. Both the mother and the father provide care for human offspring, in contrast to other primates, where parental care
3537-777: A very important role in ovarian function, independent from cognitive/neurological effects. Minor expansions of CGG repeats that do not cause fragile X syndrome are associated with an increased risk for premature ovarian aging , also called occult primary ovarian insufficiency, a condition in which women prematurely deplete their ovarian function. A very specific sub-genotype of FMR1 has been found to be associated with polycystic ovarian syndrome (PCOS). The gene expression, called heterozygous-normal/low may cause PCOS-like excessive follicle activity and hyperactive ovarian function when women are younger. FMR1 has been shown to interact with: Human Humans ( Homo sapiens , meaning "thinking man" or "wise man") or modern humans are
3668-406: A wide variety of plant and animal material. Human groups have adopted a range of diets from purely vegan to primarily carnivorous . In some cases, dietary restrictions in humans can lead to deficiency diseases ; however, stable human groups have adapted to many dietary patterns through both genetic specialization and cultural conventions to use nutritionally balanced food sources. The human diet
3799-505: Is RhoA , a protein that also modulates the regulation and timing of cell division. In the context of activity in neurons, RhoA is activated in the following manner: once calcium has entered a cell through NMDA receptors , it binds to calmodulin and activates CaMKII , which leads to the activation of RhoA. The activation of the RhoA protein will activate ROCK, a RhoA kinase, which leads to the stimulation of LIM kinase , which in turn inhibits
3930-511: Is 38 weeks, but a normal pregnancy can vary by up to 37 days. Embryonic development in the human covers the first eight weeks of development; at the beginning of the ninth week the embryo is termed a fetus . Humans are able to induce early labor or perform a caesarean section if the child needs to be born earlier for medical reasons. In developed countries, infants are typically 3–4 kg (7–9 lb) in weight and 47–53 cm (19–21 in) in height at birth. However, low birth weight
4061-754: Is a conserved motif which characterizes many RNA-binding proteins. Mutagenesis of this domain resulted in impaired FMRP binding to RNA. FMRP has been shown to inhibit translation of mRNA. Mutation of the FMRP protein resulted in the inability to repress translation as opposed to the wild-type counterpart which was able to do so. As previously mentioned, mGluR stimulation is associated with increased FMRP protein levels. In addition, mGluR stimulation results in increased levels of FMRP target mRNAs. A study found basal levels of proteins encoded by these target mRNAs to be significantly elevated and improperly regulated in FMRP deficient mice. FMRP translation repression acts by inhibiting
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4192-410: Is a continuum of shapes between these categories. The variable spine shape and volume is thought to be correlated with the strength and maturity of each spine-synapse. Dendritic spines usually receive excitatory input from axons, although sometimes both inhibitory and excitatory connections are made onto the same spine head . Excitatory axon proximity to dendritic spines is not sufficient to predict
4323-485: Is a mixture of the two parental sets. Among the 23 pairs of chromosomes, there are 22 pairs of autosomes and one pair of sex chromosomes . Like other mammals, humans have an XY sex-determination system , so that females have the sex chromosomes XX and males have XY. Genes and environment influence human biological variation in visible characteristics, physiology, disease susceptibility and mental abilities. The exact influence of genes and environment on certain traits
4454-424: Is a population decline in the winter months of this realm. Humans established nation-states in the other seven realms, such as South Africa , India , Russia , Australia , Fiji , United States and Brazil (each located in a different biogeographical realm). By using advanced tools and clothing , humans have been able to extend their tolerance to a wide variety of temperatures, humidities , and altitudes. As
4585-411: Is also expressed on the spine surface, and is believed to play a role in spine survival. The tip of the spine contains an electron-dense region referred to as the " postsynaptic density " (PSD). The PSD directly apposes the active zone of its synapsing axon and comprises ~10% of the spine's membrane surface area; neurotransmitters released from the active zone bind receptors in the postsynaptic density of
4716-453: Is associated with a wide spectrum of clinical phenotypes that affect more than two million people worldwide. FMRP has a diverse array of functions throughout different areas of the neuron; however these functions have not been fully characterized. FMRP has been suggested to play roles in nucleocytoplasmic shuttling of mRNA , dendritic mRNA localization, and synaptic protein synthesis . Studies of Fragile X syndrome have significantly aided in
4847-402: Is characterized by a number of morphological , developmental , physiological , and behavioral changes that have taken place since the split between the last common ancestor of humans and chimpanzees . The most significant of these adaptations are hairlessness , obligate bipedalism, increased brain size and decreased sexual dimorphism ( neoteny ). The relationship between all these changes
4978-456: Is common in developing countries, and contributes to the high levels of infant mortality in these regions. Compared with other species, human childbirth is dangerous, with a much higher risk of complications and death. The size of the fetus's head is more closely matched to the pelvis than in other primates. The reason for this is not completely understood, but it contributes to a painful labor that can last 24 hours or more. The chances of
5109-421: Is dangerous, with a high risk of complications and death . Often, both the mother and the father provide care for their children, who are helpless at birth . Humans have a large, highly developed, and complex prefrontal cortex , the region of the brain associated with higher cognition. Humans are highly intelligent and capable of episodic memory ; they have flexible facial expressions, self-awareness , and
5240-436: Is further evidenced by the observation of dendritic spine elongation following mGluR stimulation. Furthermore, mGluR activation results in the synthesis of FMRP near synapses . The produced FMRP associates with polyribosomal complexes after mGluR stimulation, proposing the involvement of Fragile X Messenger Ribonucleoprotein in the process of translation . This further advocates a role for FMRP in synaptic protein synthesis and
5371-479: Is generally aging, with the median age around 40 years. In the developing world , the median age is between 15 and 20 years. While one in five Europeans is 60 years of age or older, only one in twenty Africans is 60 years of age or older. In 2012, the United Nations estimated that there were 316,600 living centenarians (humans of age 100 or older) worldwide. Humans are omnivorous , capable of consuming
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5502-443: Is inherited only from the mother, geneticists have concluded that the last female common ancestor whose genetic marker is found in all modern humans, the so-called mitochondrial Eve , must have lived around 90,000 to 200,000 years ago. Most human reproduction takes place by internal fertilization via sexual intercourse , but can also occur through assisted reproductive technology procedures. The average gestation period
5633-714: Is mediated by the presence of an abundance of proteins, especially kinases, that are localized to the postsynaptic density. These include calcium -dependent calmodulin , CaMKII (calmodulin-dependent protein kinase II), PKC (Protein Kinase C), PKA (Protein Kinase A), Protein Phosphatase-1 (PP-1), and Fyn tyrosine kinase . Certain signallers, such as CaMKII, are upregulated in response to activity. Spines are particularly advantageous to neurons by compartmentalizing biochemical signals. This can help to encode changes in
5764-408: Is mostly done by the mother. Helpless at birth , humans continue to grow for some years, typically reaching sexual maturity at 15 to 17 years of age. The human life span has been split into various stages ranging from three to twelve. Common stages include infancy , childhood , adolescence , adulthood and old age . The lengths of these stages have varied across cultures and time periods but
5895-645: Is necessary for the transient phase and most likely the sustained phase as well of spine growth. Cdc42 has been implicated in many different functions including dendritic growth, branching, and branch stability. Calcium influx into the cell through NMDA receptors binds to calmodulin and activates the Ca2+/calmodulin-dependent protein kinases II (CaMKII). In turn, CaMKII is activated and this activates Cdc42, after which no feedback signaling occurs upstream to calcium and CaMKII. If tagged with monomeric-enhanced green fluorescent protein, one can see that
6026-521: Is not well understood. While no humans – not even monozygotic twins – are genetically identical, two humans on average will have a genetic similarity of 99.5%-99.9%. This makes them more homogeneous than other great apes, including chimpanzees. This small variation in human DNA compared to many other species suggests a population bottleneck during the Late Pleistocene (around 100,000 years ago), in which
6157-768: Is primarily made of filamentous actin ( F-actin ). tubulin Monomers and microtubule-associated proteins (MAPs) are present, and organized microtubules are present. Because spines have a cytoskeleton of primarily actin, this allows them to be highly dynamic in shape and size. The actin cytoskeleton directly determines the morphology of the spine, and actin regulators, small GTPases such as Rac , RhoA , and CDC42 , rapidly modify this cytoskeleton. Overactive Rac1 results in consistently smaller dendritic spines. In addition to their electrophysiological activity and their receptor-mediated activity, spines appear to be vesicularly active and may even translate proteins . Stacked discs of
6288-425: Is prominently reflected in human culture and has led to the development of food science . Dendritic spine A dendritic spine (or spine ) is a small membrane protrusion from a neuron's dendrite that typically receives input from a single axon at the synapse . Dendritic spines serve as a storage site for synaptic strength and help transmit electrical signals to the neuron's cell body. Most spines have
6419-544: Is required in some way for this process. After the transient changes described above take place, the spine's volume decreases until it is elevated by 70 to 80 percent of the original volume. This sustained change in structural plasticity will last about thirty minutes. Once again, administration of C3 transferase and Glycyl-H1152 suppressed this growth, suggesting that the Rho-Rock pathway is necessary for more persistent increases in spinal volume. In addition, administration of
6550-445: Is the subject of ongoing debate. Hylobatidae ( gibbons ) Pongo abelii Pongo tapanuliensis Pongo pygmaeus Gorilla gorilla Gorilla beringei Pan troglodytes Pan paniscus Homo sapiens (humans) Until about 12,000 years ago, all humans lived as hunter-gatherers . The Neolithic Revolution (the invention of agriculture ) first took place in Southwest Asia and spread through large parts of
6681-654: Is typified by an unusually rapid growth spurt during adolescence. Human females undergo menopause and become infertile at around the age of 50. It has been proposed that menopause increases a woman's overall reproductive success by allowing her to invest more time and resources in her existing offspring, and in turn their children (the grandmother hypothesis ), rather than by continuing to bear children into old age. The life span of an individual depends on two major factors, genetics and lifestyle choices. For various reasons, including biological/genetic causes, women live on average about four years longer than men. As of 2018 ,
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#17327723143006812-548: The British Empire expanded to become the world's largest empire . A tenuous balance of power among European nations collapsed in 1914 with the outbreak of the First World War , one of the deadliest conflicts in history. In the 1930s, a worldwide economic crisis led to the rise of authoritarian regimes and a Second World War , involving almost all of the world's countries . The war's destruction led to
6943-580: The Caral–Supe civilization is the oldest complex civilization in the Americas. Astronomy and mathematics were also developed and the Great Pyramid of Giza was built. There is evidence of a severe drought lasting about a hundred years that may have caused the decline of these civilizations, with new ones appearing in the aftermath. Babylonians came to dominate Mesopotamia while others, such as
7074-511: The Church would provide centralized authority and education. In the Middle East, Islam became the prominent religion and expanded into North Africa. It led to an Islamic Golden Age , inspiring achievements in architecture , the revival of old advances in science and technology, and the formation of a distinct way of life. The Christian and Islamic worlds would eventually clash, with
7205-474: The Homo genus. The name " Homo sapiens " means 'wise man' or 'knowledgeable man'. There is disagreement if certain extinct members of the genus, namely Neanderthals , should be included as a separate species of humans or as a subspecies of H. sapiens . Human is a loanword of Middle English from Old French humain , ultimately from Latin hūmānus , the adjectival form of homō ('man' – in
7336-579: The Kingdom of England , the Kingdom of France and the Holy Roman Empire declaring a series of holy wars to regain control of the Holy Land from Muslims . In the Americas, between 200 and 900 CE Mesoamerica was in its Classic Period , while further north, complex Mississippian societies would arise starting around 800 CE. The Mongol Empire would conquer much of Eurasia in the 13th and 14th centuries. Over this same time period,
7467-854: The Mali Empire in Africa grew to be the largest empire on the continent, stretching from Senegambia to Ivory Coast . Oceania would see the rise of the Tuʻi Tonga Empire which expanded across many islands in the South Pacific. By the late 15th century, the Aztecs and Inca had become the dominant power in Mesoamerica and the Andes , respectively. The early modern period in Europe and
7598-587: The Old World over the following millennia. It also occurred independently in Mesoamerica (about 6,000 years ago), China, Papua New Guinea , and the Sahel and West Savanna regions of Africa. Access to food surplus led to the formation of permanent human settlements , the domestication of animals and the use of metal tools for the first time in history. Agriculture and sedentary lifestyle led to
7729-652: The Poverty Point culture , Minoans and the Shang dynasty , rose to prominence in new areas. The Late Bronze Age collapse around 1200 BCE resulted in the disappearance of a number of civilizations and the beginning of the Greek Dark Ages . During this period iron started replacing bronze, leading to the Iron Age . In the 5th century BCE, history started being recorded as a discipline , which provided
7860-795: The colonization of the Americas and the Columbian Exchange . This expansion led to the Atlantic slave trade and the genocide of Native American peoples . This period also marked the Scientific Revolution , with great advances in mathematics , mechanics , astronomy and physiology . The late modern period (1800–present) saw the Technological and Industrial Revolution bring such discoveries as imaging technology , major innovations in transport and energy development . Influenced by Enlightenment ideals,
7991-423: The prefrontal cortex and the nucleus accumbens . Because significant changes in spine density occur in various brain and spinal cord diseases, this suggests a balanced state of spine dynamics in normal circumstances, which may be susceptible to disequilibrium under varying pathological conditions. There is also some evidence for loss of dendritic spines as a consequence of aging. One study using mice has noted
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#17327723143008122-424: The smooth endoplasmic reticulum (SERs) have been identified in dendritic spines. Formation of this " spine apparatus " depends on the protein synaptopodin and is believed to play an important role in calcium handling. "Smooth" vesicles have also been identified in spines, supporting the vesicular activity in dendritic spines. The presence of polyribosomes in spines also suggests protein translational activity in
8253-518: The Americas and Europe experienced a period of political revolutions known as the Age of Revolution . The Napoleonic Wars raged through Europe in the early 1800s, Spain lost most of its colonies in the New World , while Europeans continued expansion into Africa – where European control went from 10% to almost 90% in less than 50 years – and Oceania. In the 19th century,
8384-468: The CA1 region of the rat hippocampus during structural plasticity brought on by long-term potentiation stimuli. Concurrent RhoA and Cdc42 activation led to a transient increase in spine growth of up to 300% for five minutes, which decayed into a smaller but sustained growth for thirty minutes. The activation of RhoA diffused around the vicinity of the spine undergoing stimulation, and it was determined that RhoA
8515-630: The CGG segment is repeated approximately 5-44 times. Higher numbers of repeats of the CGG segment are associated with impaired cognitive and reproductive function. If a person has 45-54 repeats this is considered the "gray zone" or borderline risk, 55-200 repeats is called premutation, and more than 200 repeats is considered a full mutation of the FMR1 gene according to the American College of Medical Genetics and Genomics. The first complete DNA sequence of
8646-703: The Cdc42 binding domain of Wasp or inhibitor targeting Pak1 activation-3 (IPA3) decreases this sustained growth in volume, demonstrating that the Cdc42-Pak pathway is needed for this growth in spinal volume as well. This is important because sustained changes in structural plasticity may provide a mechanism for the encoding, maintenance, and retrieval of memories. The observations made may suggest that Rho GTPases are necessary for these processes. Dendritic spines express glutamate receptors (e.g. AMPA receptor and NMDA receptor ) on their surface. The TrkB receptor for BDNF
8777-876: The Mediterranean. In West Asia, the Achaemenid Empire 's system of centralized governance became the precursor to many later empires, while the Gupta Empire in India and the Han dynasty in China have been described as golden ages in their respective regions. Following the fall of the Western Roman Empire in 476, Europe entered the Middle Ages . During this period, Christianity and
8908-832: The Near East ( c. 1450 –1800) began with the final defeat of the Byzantine Empire , and the rise of the Ottoman Empire . Meanwhile, Japan entered the Edo period , the Qing dynasty rose in China and the Mughal Empire ruled much of India. Europe underwent the Renaissance , starting in the 15th century, and the Age of Discovery began with the exploring and colonizing of new regions. This included
9039-524: The activation of Cdc42 is limited to just the stimulated spine of a dendrite. This is because the molecule is continuously activated during plasticity and immediately inactivates after diffusing out of the spine. Despite its compartmentalized activity, Cdc42 is still mobile out of the stimulated spine, just like RhoA. Cdc42 activates PAK, which is a protein kinase that specifically phosphorylates and, therefore, inactivates ADF/cofilin. Inactivation of cofilin leads to increased actin polymerization and expansion of
9170-430: The activity of neurons have a positive effect on spine morphology. Dendritic spines are small with spine head volumes ranging 0.01 μm to 0.8 μm . Spines with strong synaptic contacts typically have a large spine head, which connects to the dendrite via a membranous neck. The most notable classes of spine shape are "thin", "stubby", "mushroom", and "bifurcated". Electron microscopy studies have shown that there
9301-439: The association of mRNA cargo and microtubules. Thus, FMRP is able to regulate transport efficacy, as well as repression of translation during transport. Finally, FMRP synthesis, ubiquitination , and proteolysis occur rapidly in response to mGluR signaling, suggesting an extremely dynamic role of the translational regulator. The FMR1 gene is located on the X chromosome and contains a repeated CGG trinucleotide. In most people,
9432-478: The available food, improving aesthetics , increasing knowledge or enhancing the exchange of resources. Humans are one of the most adaptable species, despite having a low or narrow tolerance for many of the earth's extreme environments. Currently the species is present in all eight biogeographical realms , although their presence in the Antarctic realm is very limited to research stations and annually there
9563-561: The best long-distance runners in the animal kingdom, but slower over short distances. Humans' thinner body hair and more productive sweat glands help avoid heat exhaustion while running for long distances. Compared to other apes, the human heart produces greater stroke volume and cardiac output and the aorta is proportionately larger. Like most animals, humans are a diploid and eukaryotic species. Each somatic cell has two sets of 23 chromosomes , each set received from one parent; gametes have only one set of chromosomes, which
9694-665: The collapse of most global empires, leading to widespread decolonization. Following the conclusion of the Second World War in 1945, the United States and the USSR emerged as the remaining global superpowers . This led to a Cold War that saw a struggle for global influence, including a nuclear arms race and a space race , ending in the collapse of the Soviet Union. The current Information Age , spurred by
9825-787: The combined eastern and western Roman Empire in the 4th century AD. Bubonic plagues , first recorded in the 6th century AD, reduced the population by 50%, with the Black Death killing 75–200 million people in Eurasia and North Africa alone. Human population is believed to have reached one billion in 1800. It has since then increased exponentially, reaching two billion in 1930 and three billion in 1960, four in 1975, five in 1987 and six billion in 1999. It passed seven billion in 2011 and passed eight billion in November 2022. It took over two million years of human prehistory and history for
9956-478: The continent, gradually replacing or interbreeding with local populations of archaic humans. Humans began exhibiting behavioral modernity about 160,000–70,000 years ago, and possibly earlier. This development was likely selected amidst natural climate change in Middle to Late Pleistocene Africa. The "out of Africa" migration took place in at least two waves, the first around 130,000 to 100,000 years ago,
10087-479: The dendritic spine is the basic unit of information storage, then the spine's ability to extend and retract spontaneously must be constrained. If not, information may be lost. Rho family of GTPases makes significant contributions to the process that stimulates actin polymerization, which in turn increases the size and shape of the spine. Large spines are more stable than smaller ones and may be resistant to modification by additional synaptic activity. Because changes in
10218-423: The desire to understand and influence phenomena having motivated humanity's development of science , technology , philosophy , mythology , religion , and other frameworks of knowledge ; humans also study themselves through such domains as anthropology , social science , history , psychology , and medicine . There are estimated to be more than eight billion living humans . Although some scientists equate
10349-516: The development of the Internet and Artificial Intelligence systems, sees the world becoming increasingly globalized and interconnected. Early human settlements were dependent on proximity to water and – depending on the lifestyle – other natural resources used for subsistence , such as populations of animal prey for hunting and arable land for growing crops and grazing livestock. Modern humans, however, have
10480-469: The dynamics of the DNA damage response machinery during spermatogenesis . The FMR1 gene can be found on the long (q) arm of the X chromosome at position 27.3, from base pair 146,699,054 to base pair 146,738,156 Almost all cases of fragile X syndrome are caused by expansion of the CGG trinucleotide repeat in the FMR1 gene. In these cases, CGG is abnormally repeated from 200 to more than 1,000 times. As
10611-640: The early 20th century, there has been continuous human presence in Antarctica through research stations and, since 2000, in space through habitation on the International Space Station . All modern humans are classified into the species Homo sapiens , coined by Carl Linnaeus in his 1735 work Systema Naturae . The generic name " Homo " is a learned 18th-century derivation from Latin homō , which refers to humans of either sex. The word human can refer to all members of
10742-685: The emergence of early civilizations . An urban revolution took place in the 4th millennium BCE with the development of city-states , particularly Sumerian cities located in Mesopotamia . It was in these cities that the earliest known form of writing, cuneiform script , appeared around 3000 BCE. Other major civilizations to develop around this time were Ancient Egypt and the Indus Valley Civilisation . They eventually traded with each other and invented technology such as wheels, plows and sails. Emerging by 3000 BCE,
10873-615: The formation and stabilization of new spines while destabilizing old spines, suggesting that the learning of a new skill involves a rewiring process of neural circuits. Since the extent of spine remodeling correlates with success of learning, this suggests a crucial role of synaptic structural plasticity in memory formation. In addition, changes in spine stability and strengthening occur rapidly and have been observed within hours after training. Conversely, while enrichment and training are related to increases in spine formation and stability, long-term sensory deprivation leads to an increase in
11004-566: The genomes of 1,184 individuals from 11 populations and identified 1.6 million single nucleotide polymorphisms . African populations harbor the highest number of private genetic variants. While many of the common variants found in populations outside of Africa are also found on the African continent, there are still large numbers that are private to these regions, especially Oceania and the Americas . By 2010 estimates, humans have approximately 22,000 genes. By comparing mitochondrial DNA , which
11135-595: The global average life expectancy at birth of a girl is estimated to be 74.9 years compared to 70.4 for a boy. There are significant geographical variations in human life expectancy, mostly correlated with economic development – for example, life expectancy at birth in Hong Kong is 87.6 years for girls and 81.8 for boys, while in the Central African Republic , it is 55.0 years for girls and 50.6 for boys. The developed world
11266-512: The growth of synaptic connections. The loss of FMRP results in an abnormal dendritic spine phenotype. Specifically, deletion of the FMR1 gene in a sample of mice resulted in an increase in spine synapse number. The proposed mechanism of FMRP's effect upon synaptic plasticity are through its role as a negative regulator of translation. FMRP is an RNA-binding protein which associates with polyribosomes . The RNA-binding abilities of FMRP are dependent upon its KH domains and RGG boxes . The KH domain
11397-459: The half-life of spines increases. This stabilization occurs due to a developmentally regulated slow-down of spine elimination, a process which may underlie the stabilization of memories in maturity. Experience-induced changes in dendritic spine stability also point to spine turnover as a mechanism involved in the maintenance of long-term memories, though it is unclear how sensory experience affects neural circuitry. Two general models might describe
11528-443: The human lifestyle. Genes and the environment influence human biological variation in visible characteristics, physiology , disease susceptibility, mental abilities, body size, and life span. Though humans vary in many traits, humans are among the least genetically diverse species. Any two humans are at least 99.5% genetically similar. Humans are sexually dimorphic : generally, males have greater body strength and females have
11659-555: The human population to reach one billion and only 207 years more to grow to 7 billion. The combined biomass of the carbon of all the humans on Earth in 2018 was estimated at 60 million tons, about 10 times larger than that of all non-domesticated mammals. In 2018, 4.2 billion humans (55%) lived in urban areas, up from 751 million in 1950. The most urbanized regions are Northern America (82%), Latin America (81%), Europe (74%) and Oceania (68%), with Africa and Asia having nearly 90% of
11790-517: The human population was reduced to a small number of breeding pairs. The forces of natural selection have continued to operate on human populations, with evidence that certain regions of the genome display directional selection in the past 15,000 years. The human genome was first sequenced in 2001 and by 2020 hundreds of thousands of genomes had been sequenced. In 2012 the International HapMap Project had compared
11921-575: The impact of experience on structural plasticity. On the one hand, experience and activity may drive the discrete formation of relevant synaptic connections that store meaningful information in order to allow for learning. On the other hand, synaptic connections may be formed in excess, and experience and activity may lead to the pruning of extraneous synaptic connections. In lab animals of all ages, environmental enrichment has been related to dendritic branching, spine density, and overall number of synapses. In addition, skill training has been shown to lead to
12052-492: The increase in size of spine heads. Theoreticians have for decades hypothesized about the potential electrical function of spines, yet our inability to examine their electrical properties has until recently stopped theoretical work from progressing too far. Recent advances in imaging techniques along with increased use of two-photon glutamate uncaging have led to a wealth of new discoveries; we now suspect that there are voltage-dependent sodium, potassium, and calcium channels in
12183-475: The initiation of translation. FMRP directly binds CYFIP1 , which in turn binds the translation initiation factor eIF4E . The FMRP-CYFIP1 complex prohibits eIF4E-dependent initiation, thereby acting to repress translation. When applied to the observed phenotype in fragile X Syndrome, the excess protein levels and reduction of translational control can be explained by the loss of translational repression by FMRP in fragile X syndrome. FMRP acts to control translation of
12314-567: The late Miocene epoch. During this split, chromosome 2 was formed from the joining of two other chromosomes, leaving humans with only 23 pairs of chromosomes, compared to 24 for the other apes. Following their split with chimpanzees and bonobos, the hominins diversified into many species and at least two distinct genera. All but one of these lineages – representing the genus Homo and its sole extant species Homo sapiens – are now extinct. The genus Homo evolved from Australopithecus . Though fossils from
12445-602: The maintenance of memory over a lifetime. Age-dependent changes in the rate of spine turnover suggest that spine stability impacts developmental learning. In youth, dendritic spine turnover is relatively high and produces a net loss of spines. This high rate of spine turnover may characterize critical periods of development and reflect learning capacity in adolescence—different cortical areas exhibit differing levels of synaptic turnover during development, possibly reflecting varying critical periods for specific brain regions. In adulthood, however, most spines remain persistent, and
12576-501: The most common and widespread species of primate , and the last surviving species of the genus Homo . They are great apes characterized by their hairlessness , bipedalism , and high intelligence . Humans have large brains , enabling more advanced cognitive skills that enable them to thrive and adapt in varied environments, develop highly complex tools , and form complex social structures and civilizations . Humans are highly social , with individual humans tending to belong to
12707-427: The most stable. Spine maintenance and plasticity is activity-dependent and activity-independent. BDNF partially determines spine levels, and low levels of AMPA receptor activity is necessary to maintain spine survival, and synaptic activity involving NMDA receptors encourages spine growth. Furthermore, two-photon laser scanning microscopy and confocal microscopy have shown that spine volume changes depending on
12838-624: The nature and importance of spine turnover. After stroke , a marked increase in structural plasticity occurs near the trauma site, and a five- to eightfold increase from control rates in spine turnover has been observed. Dendrites disintegrate and reassemble rapidly during ischemia —as with stroke, survivors showed an increase in dendritic spine turnover. While a net loss of spines is observed in Alzheimer's disease and cases of intellectual disability , cocaine and amphetamine use have been linked to increases in dendritic branching and spine density in
12969-402: The next two minutes, the volume of the stimulated spine can expand to 300 percent of its original size. However, this change in spine morphology is only temporary; the volume of the spine decreases after five minutes. Administration of C3 transferase, a Rho inhibitor, or glycyl-H1152, a Rock inhibitor, inhibits the transient expansion of the spine, indicating that activation of the Rho-Rock pathway
13100-522: The number of spines and their maturity. The ratio of matured to immature spines is important in their signaling, as immature spines have impaired synaptic signaling. Fragile X syndrome is characterized by an overabundance of immature spines that have multiple filopodia in cortical dendrites. Dendritic spines were first described at the end of the 19th century by Santiago Ramón y Cajal on cerebellar neurons. Ramón y Cajal then proposed that dendritic spines could serve as contacting sites between neurons. This
13231-414: The number of spines on Purkinje neuron dendrites is an order of magnitude larger. The cytoskeleton of dendritic spines is particularly important in their synaptic plasticity ; without a dynamic cytoskeleton, spines would be unable to rapidly change their volumes or shapes in responses to stimuli. These changes in shape might affect the electrical properties of the spine. The cytoskeleton of dendritic spines
13362-559: The ongoing mass extinction of other forms of life. Within the last century, humans have explored challenging environments such as Antarctica , the deep sea , and outer space . Human habitation within these hostile environments is restrictive and expensive, typically limited in duration, and restricted to scientific , military , or industrial expeditions. Humans have visited the Moon and made their presence known on other celestial bodies through human-made robotic spacecraft . Since
13493-442: The only primates to have short, relatively flush canine teeth . Humans have characteristically crowded teeth, with gaps from lost teeth usually closing up quickly in young individuals. Humans are gradually losing their third molars , with some individuals having them congenitally absent. Humans share with chimpanzees a vestigial tail, appendix , flexible shoulder joints, grasping fingers and opposable thumbs . Humans also have
13624-474: The palm of the hand and on the soles of the feet. It is estimated that the worldwide average height for an adult human male is about 171 cm (5 ft 7 in), while the worldwide average height for adult human females is about 159 cm (5 ft 3 in). Shrinkage of stature may begin in middle age in some individuals but tends to be typical in the extremely aged . Throughout history, human populations have universally become taller, probably as
13755-495: The permanent physical changes and altered synaptic connections that are linked with the processes of learning and memory. Group 1 metabotropic glutamate receptor (mGluR) signaling has been implicated in playing an important role in FMRP-dependent synaptic plasticity. Post-synaptic mGluR stimulation results in the up-regulation of protein synthesis through a second messenger system . A role for mGluR in synaptic plasticity
13886-511: The physical features seen in fragile X syndrome (such as prominent ears) and may experience mental health problems such as anxiety or depression. Premutations are associated with an increased risk of fragile X-associated tremor/ataxia syndrome (FXTAS). FXTAS is characterized by ataxia (loss of coordination), tremor , memory loss , loss of sensation in the lower extremities ( peripheral neuropathy ) and mental and behavioral changes. The disorder usually develops late in life. The FMR1 gene plays
14017-515: The population density varies from one region to another, and large stretches of surface are almost completely uninhabited, like Antarctica and vast swathes of the ocean. Most humans (61%) live in Asia; the remainder live in the Americas (14%), Africa (14%), Europe (11%), and Oceania (0.5%). Estimates of the population at the time agriculture emerged in around 10,000 BC have ranged between 1 million and 15 million. Around 50–60 million people lived in
14148-662: The presence of a synapse, as demonstrated by the Lichtman lab in 2015. Spines are found on the dendrites of most principal neurons in the brain, including the pyramidal neurons of the neocortex , the medium spiny neurons of the striatum , and the Purkinje cells of the cerebellum . Dendritic spines occur at a density of up to 5 spines/1 μm stretch of dendrite. Hippocampal and cortical pyramidal neurons may receive tens of thousands of mostly excitatory inputs from other neurons onto their equally numerous spines, whereas
14279-610: The production of spines to handle specialized postsynaptic contact with the presynaptic protrusions. Spines, however, require maturation after formation. Immature spines have impaired signaling capabilities, and typically lack "heads" (or have very small heads), only necks, while matured spines maintain both heads and necks. Emerging research has indicate abnormalities in spine density in anxiety disorders. Cognitive disorders such as ADHD , Alzheimer's disease , autism , intellectual disability , and fragile X syndrome , may be resultant from abnormalities in dendritic spines, especially
14410-483: The protein cofilin . Cofilin's function is to reorganize the actin cytoskeleton of a cell; namely, it depolymerizes actin segments and thus inhibits the growth of growth cones and the repair of axons. A study conducted by Murakoshi et al. in 2011 implicated the Rho GTPases RhoA and Cdc42 in dendritic spine morphogenesis. Both GTPases were quickly activated in single dendritic spines of pyramidal neurons in
14541-484: The rate of spine elimination and therefore impacts long-term neural circuitry. Upon restoring sensory experience after deprivation in adolescence, spine elimination is accelerated, suggesting that experience plays an important role in the net loss of spines during development. In addition, other sensory deprivation paradigms—such as whisker trimming—have been shown to increase the stability of new spines. Research in neurological diseases and injuries shed further light on
14672-493: The repeat expansion in someone with the full mutation was generated by scientists in 2012 using SMRT sequencing . This is an example of a Trinucleotide repeat disorder . Trinucleotide repeat expansion is likely a consequence of strand slippage either during DNA repair or DNA replication . FMRP is a chromatin -binding protein that functions in the DNA damage response. FMRP occupies sites on meiotic chromosomes and regulates
14803-404: The second ( Southern Dispersal ) around 70,000 to 50,000 years ago. H. sapiens proceeded to colonize all the continents and larger islands, arriving in Eurasia 125,000 years ago, Australia around 65,000 years ago, the Americas around 15,000 years ago, and remote islands such as Hawaii , Easter Island , Madagascar , and New Zealand in the years 300 to 1280 CE. Human evolution was not
14934-547: The sense of humanity). The native English term man can refer to the species generally (a synonym for humanity ) as well as to human males. It may also refer to individuals of either sex. Despite the fact that the word animal is colloquially used as an antonym for human , and contrary to a common biological misconception , humans are animals . The word person is often used interchangeably with human , but philosophical debate exists as to whether personhood applies to all humans or all sentient beings , and further if
15065-484: The shape and size of dendritic spines are correlated with the strength of excitatory synaptic connections and heavily depend on remodeling of its underlying actin cytoskeleton, the specific mechanisms of actin regulation, and therefore the Rho family of GTPases, are integral to the formation, maturation, and plasticity of dendritic spines and to learning and memory. One of the major Rho GTPases involved in spine morphogenesis
15196-533: The spine head. Evidence from calcium imaging experiments ( two-photon microscopy ) and from compartmental modelling indicates that spines with high resistance necks experience larger calcium transients during synaptic activity. Dendritic spines can develop directly from dendritic shafts or from dendritic filopodia . During synaptogenesis , dendrites rapidly sprout and retract filopodia, small membrane organelle-lacking membranous protrusions. Recently, I-BAR protein MIM
15327-470: The spine heads. Cable theory provides the theoretical framework behind the most "simple" method for modelling the flow of electrical currents along passive neural fibres. Each spine can be treated as two compartments, one representing the neck, the other representing the spine head. The compartment representing the spine head alone should carry the active properties. To facilitate the analysis of interactions between many spines, Baer & Rinzel formulated
15458-412: The spine itself, not just in the dendrite. The morphogenesis of dendritic spines is critical to the induction of long-term potentiation (LTP). The morphology of the spine depends on the states of actin , either in globular (G-actin) or filamentous (F-actin) forms. The role of Rho family of GTPases and its effects in the stability of actin and spine motility has important implications for memory. If
15589-464: The spine's volume. Activation of Cdc42 is required for this increase in spinal volume to be sustained. Murakoshi, Wang, and Yasuda (2011) examined the effects of Rho GTPase activation on the structural plasticity of single dendritic spines elucidating differences between the transient and sustained phases. Applying a low-frequency train of two-photon glutamate uncaging in a single dendritic spine can elicit rapid activation of both RhoA and Cdc42. During
15720-409: The spine. Half of the synapsing axons and dendritic spines are physically tethered by calcium -dependent cadherin , which forms cell-to-cell adherent junctions between two neurons. Glutamate receptors (GluRs) are localized to the postsynaptic density, and are anchored by cytoskeletal elements to the membrane. They are positioned directly above their signalling machinery, which is typically tethered to
15851-420: The state of an individual synapse without necessarily affecting the state of other synapses of the same neuron. The length and width of the spine neck has a large effect on the degree of compartmentalization, with thin spines being the most biochemically isolated spines. Dendritic spines are very "plastic", that is, spines change significantly in shape, volume, and number in small time courses. Because spines have
15982-433: The term "humans" with all members of the genus Homo , in common usage it generally refers to Homo sapiens , the only extant member. All other members of the genus Homo , which are now extinct, are known as archaic humans , and the term "modern human" is used to distinguish Homo sapiens from archaic humans. Anatomically modern humans emerged around 300,000 years ago in Africa, evolving from Homo heidelbergensis or
16113-427: The transition are scarce, the earliest members of Homo share several key traits with Australopithecus . The earliest record of Homo is the 2.8 million-year-old specimen LD 350-1 from Ethiopia , and the earliest named species are Homo habilis and Homo rudolfensis which evolved by 2.3 million years ago. H. erectus (the African variant is sometimes called H. ergaster ) evolved 2 million years ago and
16244-477: The transportation of mRNA complexes to synapses for local protein synthesis. FMRP granules have been shown to localize with MAP1B mRNA and ribosomal RNA in dendrites, suggesting this complex as a whole may need to be transported to dendrites for local protein synthesis. In addition, microtubules were found to be a necessary component for the mGluR-dependent translocation of FMRP into dendrites. FMRP may play an additional role in local protein synthesis by aiding in
16375-452: The types of stimuli that are presented to a synapse. Spine plasticity is implicated in motivation , learning , and memory . In particular, long-term memory is mediated in part by the growth of new dendritic spines (or the enlargement of pre-existing spines) to reinforce a particular neural pathway. Because dendritic spines are plastic structures whose lifespan is influenced by input activity, spine dynamics may play an important role in
16506-491: The underside of the plasma membrane, allowing signals transmitted by the GluRs into the cytosol to be further propagated by their nearby signalling elements to activate signal transduction cascades . The localization of signalling elements to their GluRs is particularly important in ensuring signal cascade activation, as GluRs would be unable to affect particular downstream effects without nearby signallers. Signalling from GluRs
16637-422: The understanding of the functionality of FMRP through the observed effects of FMRP loss on neurons. A mouse model of Fragile X Messenger Ribonucleoprotein implicated the involvement of FMRP in synaptic plasticity . Synaptic plasticity requires the production of new proteins in response to activation of synaptic receptors . It is the production of proteins in response to stimulation which is hypothesized to allow for
16768-440: The world's 3.4 billion rural population. Problems for humans living in cities include various forms of pollution and crime , especially in inner city and suburban slums . Most aspects of human physiology are closely homologous to corresponding aspects of animal physiology. The dental formula of humans is: 2.1.2.3 2.1.2.3 . Humans have proportionately shorter palates and much smaller teeth than other primates. They are
16899-419: Was demonstrated more than 50 years later thanks to the emergence of electron microscopy. Until the development of confocal microscopy on living tissues, it was commonly admitted that spines were formed during embryonic development and then would remain stable after birth. In this paradigm, variations of synaptic weight were considered as sufficient to explain memory processes at the cellular level. But since about
17030-424: Was found to contribute to the initiation process. During the first week of birth, the brain is predominated by filopodia, which eventually develop synapses. However, after this first week, filopodia are replaced by spiny dendrites but also small, stubby spines that protrude from spiny dendrites. In the development of certain filopodia into spines, filopodia recruit presynaptic contact to the dendrite, which encourages
17161-402: Was the first archaic human species to leave Africa and disperse across Eurasia. H. erectus also was the first to evolve a characteristically human body plan . Homo sapiens emerged in Africa around 300,000 years ago from a species commonly designated as either H. heidelbergensis or H. rhodesiensis , the descendants of H. erectus that remained in Africa. H. sapiens migrated out of
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