/page/2
scienceyoucanlove:

Keeping Viral Load Low
By Thomas Deerinck, NCMIR, USCD
Over the past 30 years, the combined efforts of scientists and clinicians have delivered remarkable successes in HIV therapeutics. Since 1987, the FDA has approved more than 30 antiviral drugs, including 12 HIV protease inhibitors and one integrase inhibitor. These drugs stop ~99% of viral replication, essentially transforming HIV infection from a deadly disease to a chronic one. What will the next 30 years bring?
Image: Here numerous HIV-1 particles leave a cultured HeLa cell. These viruses lack their vpu gene and thus can’t detach from the cell’s tethering factor, BST2. Each viron particle is ~120nm in diameter. The image was captured with a Zeiss Merlin ultra high-resolution scanning electron microscope. The cells were fixed, dehydrated, critical-point dried, and lightly sputter-coated with gold/palladium.
through Cell.com

scienceyoucanlove:

Keeping Viral Load Low

By Thomas Deerinck, NCMIR, USCD

Over the past 30 years, the combined efforts of scientists and clinicians have delivered remarkable successes in HIV therapeutics. Since 1987, the FDA has approved more than 30 antiviral drugs, including 12 HIV protease inhibitors and one integrase inhibitor. These drugs stop ~99% of viral replication, essentially transforming HIV infection from a deadly disease to a chronic one. What will the next 30 years bring?

Image: Here numerous HIV-1 particles leave a cultured HeLa cell. These viruses lack their vpu gene and thus can’t detach from the cell’s tethering factor, BST2. Each viron particle is ~120nm in diameter. The image was captured with a Zeiss Merlin ultra high-resolution scanning electron microscope. The cells were fixed, dehydrated, critical-point dried, and lightly sputter-coated with gold/palladium.

through Cell.com

vintagegal:

Illustration by Ren Wicks c. 1964

vintagegal:

Illustration by Ren Wicks c. 1964

(via crystalquelin)

dearninety:

31.8 x 40.9 cm, Acrylic on Canvas

dearninety:

31.8 x 40.9 cm, Acrylic on Canvas

(via onlinebabe)


Kimagure Orange Road OVA, episode 3: “I was a Cat; I was a Fish”

Kimagure Orange Road OVA, episode 3: “I was a Cat; I was a Fish”

(Source: animeismywhore, via 80sanime)

princessjohnegbert:



Fun Historical Fact: There used to be more gay and lesbian content in early silent films until religious groups protested resulting in “decency standards.”

princessjohnegbert:

Fun Historical Fact: There used to be more gay and lesbian content in early silent films until religious groups protested resulting in “decency standards.”

(Source: string-a-plume, via kim-jong-chill)

iheartmyart:

Smithe, Lead Us - Serigrafía (80 x 60 cm.), 2013  *Buy Here*
(via gameroomrecordings)

iheartmyart:

Smithe, Lead Us - Serigrafía (80 x 60 cm.), 2013  *Buy Here*

(via gameroomrecordings)

(Source: smitheone)

bpod-mrc:

27 July 2014
Kettling Proteins
Prions are infectious proteins that can cause deadly diseases like bovine spongiform encephalopathy, or mad cow disease. They also infect yeast cells and this simple fungus has been found to produce a protein, Btn2, that targets prions and kettles them into a small area inside the cell, rather like the way riot police control an unruly crowd. When the cell divides, one of the two offspring is free from prions and can thrive. Intriguingly, Btn2 has similarities to human hook proteins, which play an important role in positioning components inside human cells so they can divide correctly. Pictured are three yeast colonies, the top right producing Btn2 and with mainly healthy cells (stained red) and some infected by prions (white). The lower colony is producing Cur1, a protein allied to Btn2 and has some healthy cells, while the top left colony is producing neither protein and is heavily infected.
Written by Mick Warwicker
—
Image by Reed Wickner and colleaguesNational Institutes of Health, USAOriginally published under a Creative Commons Licence (BY 4.0)Research published in PNAS, June 2014
—
You can also follow BPoD on Twitter and Facebook

bpod-mrc:

27 July 2014

Kettling Proteins

Prions are infectious proteins that can cause deadly diseases like bovine spongiform encephalopathy, or mad cow disease. They also infect yeast cells and this simple fungus has been found to produce a protein, Btn2, that targets prions and kettles them into a small area inside the cell, rather like the way riot police control an unruly crowd. When the cell divides, one of the two offspring is free from prions and can thrive. Intriguingly, Btn2 has similarities to human hook proteins, which play an important role in positioning components inside human cells so they can divide correctly. Pictured are three yeast colonies, the top right producing Btn2 and with mainly healthy cells (stained red) and some infected by prions (white). The lower colony is producing Cur1, a protein allied to Btn2 and has some healthy cells, while the top left colony is producing neither protein and is heavily infected.

Written by Mick Warwicker

Image by Reed Wickner and colleagues
National Institutes of Health, USA
Originally published under a Creative Commons Licence (BY 4.0)
Research published in PNAS, June 2014

You can also follow BPoD on Twitter and Facebook

gyclli:



Dawn in Bali ~ Blue beach, Indonesia
Dawn in Bali / Ko Zaw

gyclli:

Dawn in Bali ~ Blue beach, Indonesia

Dawn in Bali /

(via eswynn)

ifuckingloveminerals:

Segnitite
Clara Mine, Rankach valley, Oberwolfach, Wolfach, Black Forest, Baden-Württemberg, Germany

ifuckingloveminerals:

Segnitite

Clara Mine, Rankach valley, Oberwolfach, Wolfach, Black Forest, Baden-Württemberg, Germany

(via mushroooms)

neurosciencestuff:

(Image caption: Granule cells connect with other cells via long projections (dendrites). The actual junctions (synapses) are located on thorn-like protuberances called “spines”. Spines are shown in green in the computer reconstruction. Credit: DZNE/Michaela Müller)
A protein couple controls flow of information into the brain’s memory center
Neuroscientists in Bonn and Heidelberg have succeeded in providing new insights into how the brain works. Researchers at the DZNE and the German Cancer Research Center (DKFZ) analyzed tissue samples from mice to identify how two specific proteins, ‘CKAMP44’ and ‘TARP Gamma-8’, act upon the brain’s memory center. These molecules, which have similar counterparts in humans, affect the connections between nerve cells and influence the transmission of nerve signals into the hippocampus, an area of the brain that plays a significant role in learning processes and the creation of memories. The results of the study have been published in the journal Neuron.
Brain function depends on the active communication between nerve cells, known as neurons. For this purpose, neurons are woven together into a dense network where they constantly relay signals to one another. However, neurons do not form direct contacts with each other. Instead they are separated by an extremely narrow gap, known as the synapse. This gap is bridged by ‘neurotransmitters’, which carry nerve signals from one cell to the next.
Docking stations

Specific molecular complexes in the cell’s outer shell, so-called ‘receptors’, receive the signal by binding the neurotransmitters. This triggers an electrical impulse in the receptor-bearing cell and thus the nerve signal has moved on one neuron further.
In the current study, a team led by Dr Jakob von Engelhardt focused on the AMPA receptors. These bind the neurotransmitter glutamate and are particularly common in the brain. “We looked at AMPA receptors in an area of the brain, which constitutes the main entrance to the hippocampus,” explains von Engelhardt, who works for the DZNE and DKFZ. “The hippocampus is responsible for learning and memory formation. Among other things it processes and combines sensory perception. We therefore asked ourselves how the flow of information into the hippocampus is controlled.”
A pair of helpers
Dr von Engelhardt’s research team specifically focused on two protein molecules: ‘CKAMP44’ and ‘TARP Gamma-8’. These proteins are present, along with AMPA receptors, in the ‘granule’ cells, which are neurons that receive signals from areas outside of the hippocampus. It was already known that these proteins form protein complexes with AMPA receptors. “We have now found out that they exert a significant influence on the functioning of glutamate receptors. Each in its own way, as chemically they are completely different,” says the neuroscientist. “We identified that the ability of a nerve cell to receive signals doesn’t depend solely on the actual receptors; CKAMP44 and TARP Gamma-8 are just as important. Their function cannot be separated from that of the receptors.”
This was the result of an analysis in which the researchers compared brain tissue from mice with a natural genotype with brain tissue from genetically modified mice. Neurons in the genetically modified animals were not able to produce either CKAMP44 or TARP Gamma-8 or both.
Long-term effect
The researchers discovered, among other things, that both proteins promote the transportation of glutamate receptors to the cell surface. “This means they influence how receptive the nerve cell is to incoming signals,” says von Engelhardt.
However, the number of receptors and thus the signal reception can be altered by neuronal activity. The von Engelhardt group found that in this regard the auxiliary molecules have different effects: TARP Gamma-8 is essential to ensure that more AMPA receptors are integrated into the synapse following a plasticity induction protocol, whereas CKAMP44 plays no role in this context. “Synapses alter their communication depending on their activity. This ability is called plasticity. Some of the changes involved are only temporary, others may last longer,” explains von Engelhardt. “TARP Gamma-8 influences long-term plasticity. It makes the cell able to strengthen synaptic communication for a prolonged time-period. The larger the number of receptors on the receiving side of the synapse, the better the neuronal connection.”
The number of receptors doesn’t change suddenly, but remains largely stable for a certain amount of time. “This condition may last for hours, days or even longer. This long-term effect is essential for the creation of memories. We can only remember things if the connections between neurons undergo a long-lasting change,” says the scientist.
Fast sequence of signals
However, CKAMP44 and TARP Gamma-8 also act over shorter periods of time. The research team discovered that the molecules affect how quickly the AMPA receptors return to a receptive state. “If glutamate has docked on to a receptor, it takes a while until the receptor can react to the next neurotransmitter. CKAMP44 lengthens this period. In contrast, TARP Gamma-8 helps the receptor to recover more quickly,” says von Engelhardt.
Hence, CKAMP44 temporarily weakens the synaptic connection, while TARP Gamma-8 strengthens it. Through the interplay of these proteins the synapse is able to tune its sensitivity to a specific level. This condition can last from milliseconds to a few seconds before the strength of the connection is again adapted. Specialists refer to this as “short-term plasticity”.
“These molecules ultimately influence how well the nerve cell is able to react to a rapid succession of signals,” the scientist summarises the findings. “Such a rapid firing enables neuronal networks to synchronize their activity, which is a common process in the brain.”
Sensitive balance
Much to the researchers’ surprise, it turned out that the two proteins influence not only the synapse but also the shape of the nerve cells. In the absence of these auxiliary molecules, the neurons have fewer dendrites to establish contact with other nerve cells. “The organism can use CKAMP44 and TARP Gamma-8 molecules to regulate neuronal connections in a number of ways,” von Engelhardt says. “This ability depends on the balance between the partners, as to some extent they have a contrary effect. The way in which the neurons of the hippocampus react to signals from other regions of the brain is therefore highly dependent on the presence and the expression ratio of these molecules.”
Since the two molecules act directly on the structure and function of synapses of granule cells, Jakob von Engelhardt considers it probable that they also have an influence on learning and memory.

neurosciencestuff:

(Image caption: Granule cells connect with other cells via long projections (dendrites). The actual junctions (synapses) are located on thorn-like protuberances called “spines”. Spines are shown in green in the computer reconstruction. Credit: DZNE/Michaela Müller)

A protein couple controls flow of information into the brain’s memory center

Neuroscientists in Bonn and Heidelberg have succeeded in providing new insights into how the brain works. Researchers at the DZNE and the German Cancer Research Center (DKFZ) analyzed tissue samples from mice to identify how two specific proteins, ‘CKAMP44’ and ‘TARP Gamma-8’, act upon the brain’s memory center. These molecules, which have similar counterparts in humans, affect the connections between nerve cells and influence the transmission of nerve signals into the hippocampus, an area of the brain that plays a significant role in learning processes and the creation of memories. The results of the study have been published in the journal Neuron.

Brain function depends on the active communication between nerve cells, known as neurons. For this purpose, neurons are woven together into a dense network where they constantly relay signals to one another. However, neurons do not form direct contacts with each other. Instead they are separated by an extremely narrow gap, known as the synapse. This gap is bridged by ‘neurotransmitters’, which carry nerve signals from one cell to the next.

Docking stations

Specific molecular complexes in the cell’s outer shell, so-called ‘receptors’, receive the signal by binding the neurotransmitters. This triggers an electrical impulse in the receptor-bearing cell and thus the nerve signal has moved on one neuron further.

In the current study, a team led by Dr Jakob von Engelhardt focused on the AMPA receptors. These bind the neurotransmitter glutamate and are particularly common in the brain. “We looked at AMPA receptors in an area of the brain, which constitutes the main entrance to the hippocampus,” explains von Engelhardt, who works for the DZNE and DKFZ. “The hippocampus is responsible for learning and memory formation. Among other things it processes and combines sensory perception. We therefore asked ourselves how the flow of information into the hippocampus is controlled.”

A pair of helpers

Dr von Engelhardt’s research team specifically focused on two protein molecules: ‘CKAMP44’ and ‘TARP Gamma-8’. These proteins are present, along with AMPA receptors, in the ‘granule’ cells, which are neurons that receive signals from areas outside of the hippocampus. It was already known that these proteins form protein complexes with AMPA receptors. “We have now found out that they exert a significant influence on the functioning of glutamate receptors. Each in its own way, as chemically they are completely different,” says the neuroscientist. “We identified that the ability of a nerve cell to receive signals doesn’t depend solely on the actual receptors; CKAMP44 and TARP Gamma-8 are just as important. Their function cannot be separated from that of the receptors.”

This was the result of an analysis in which the researchers compared brain tissue from mice with a natural genotype with brain tissue from genetically modified mice. Neurons in the genetically modified animals were not able to produce either CKAMP44 or TARP Gamma-8 or both.

Long-term effect

The researchers discovered, among other things, that both proteins promote the transportation of glutamate receptors to the cell surface. “This means they influence how receptive the nerve cell is to incoming signals,” says von Engelhardt.

However, the number of receptors and thus the signal reception can be altered by neuronal activity. The von Engelhardt group found that in this regard the auxiliary molecules have different effects: TARP Gamma-8 is essential to ensure that more AMPA receptors are integrated into the synapse following a plasticity induction protocol, whereas CKAMP44 plays no role in this context. “Synapses alter their communication depending on their activity. This ability is called plasticity. Some of the changes involved are only temporary, others may last longer,” explains von Engelhardt. “TARP Gamma-8 influences long-term plasticity. It makes the cell able to strengthen synaptic communication for a prolonged time-period. The larger the number of receptors on the receiving side of the synapse, the better the neuronal connection.”

The number of receptors doesn’t change suddenly, but remains largely stable for a certain amount of time. “This condition may last for hours, days or even longer. This long-term effect is essential for the creation of memories. We can only remember things if the connections between neurons undergo a long-lasting change,” says the scientist.

Fast sequence of signals

However, CKAMP44 and TARP Gamma-8 also act over shorter periods of time. The research team discovered that the molecules affect how quickly the AMPA receptors return to a receptive state. “If glutamate has docked on to a receptor, it takes a while until the receptor can react to the next neurotransmitter. CKAMP44 lengthens this period. In contrast, TARP Gamma-8 helps the receptor to recover more quickly,” says von Engelhardt.

Hence, CKAMP44 temporarily weakens the synaptic connection, while TARP Gamma-8 strengthens it. Through the interplay of these proteins the synapse is able to tune its sensitivity to a specific level. This condition can last from milliseconds to a few seconds before the strength of the connection is again adapted. Specialists refer to this as “short-term plasticity”.

“These molecules ultimately influence how well the nerve cell is able to react to a rapid succession of signals,” the scientist summarises the findings. “Such a rapid firing enables neuronal networks to synchronize their activity, which is a common process in the brain.”

Sensitive balance

Much to the researchers’ surprise, it turned out that the two proteins influence not only the synapse but also the shape of the nerve cells. In the absence of these auxiliary molecules, the neurons have fewer dendrites to establish contact with other nerve cells. “The organism can use CKAMP44 and TARP Gamma-8 molecules to regulate neuronal connections in a number of ways,” von Engelhardt says. “This ability depends on the balance between the partners, as to some extent they have a contrary effect. The way in which the neurons of the hippocampus react to signals from other regions of the brain is therefore highly dependent on the presence and the expression ratio of these molecules.”

Since the two molecules act directly on the structure and function of synapses of granule cells, Jakob von Engelhardt considers it probable that they also have an influence on learning and memory.

scienceyoucanlove:

Keeping Viral Load Low
By Thomas Deerinck, NCMIR, USCD
Over the past 30 years, the combined efforts of scientists and clinicians have delivered remarkable successes in HIV therapeutics. Since 1987, the FDA has approved more than 30 antiviral drugs, including 12 HIV protease inhibitors and one integrase inhibitor. These drugs stop ~99% of viral replication, essentially transforming HIV infection from a deadly disease to a chronic one. What will the next 30 years bring?
Image: Here numerous HIV-1 particles leave a cultured HeLa cell. These viruses lack their vpu gene and thus can’t detach from the cell’s tethering factor, BST2. Each viron particle is ~120nm in diameter. The image was captured with a Zeiss Merlin ultra high-resolution scanning electron microscope. The cells were fixed, dehydrated, critical-point dried, and lightly sputter-coated with gold/palladium.
through Cell.com

scienceyoucanlove:

Keeping Viral Load Low

By Thomas Deerinck, NCMIR, USCD

Over the past 30 years, the combined efforts of scientists and clinicians have delivered remarkable successes in HIV therapeutics. Since 1987, the FDA has approved more than 30 antiviral drugs, including 12 HIV protease inhibitors and one integrase inhibitor. These drugs stop ~99% of viral replication, essentially transforming HIV infection from a deadly disease to a chronic one. What will the next 30 years bring?

Image: Here numerous HIV-1 particles leave a cultured HeLa cell. These viruses lack their vpu gene and thus can’t detach from the cell’s tethering factor, BST2. Each viron particle is ~120nm in diameter. The image was captured with a Zeiss Merlin ultra high-resolution scanning electron microscope. The cells were fixed, dehydrated, critical-point dried, and lightly sputter-coated with gold/palladium.

through Cell.com

vintagegal:

Illustration by Ren Wicks c. 1964

vintagegal:

Illustration by Ren Wicks c. 1964

(via crystalquelin)

dearninety:

31.8 x 40.9 cm, Acrylic on Canvas

dearninety:

31.8 x 40.9 cm, Acrylic on Canvas

(via onlinebabe)


Kimagure Orange Road OVA, episode 3: “I was a Cat; I was a Fish”

Kimagure Orange Road OVA, episode 3: “I was a Cat; I was a Fish”

(Source: animeismywhore, via 80sanime)

princessjohnegbert:



Fun Historical Fact: There used to be more gay and lesbian content in early silent films until religious groups protested resulting in “decency standards.”

princessjohnegbert:

Fun Historical Fact: There used to be more gay and lesbian content in early silent films until religious groups protested resulting in “decency standards.”

(Source: string-a-plume, via kim-jong-chill)

(Source: autosafari, via heroingranola)

iheartmyart:

Smithe, Lead Us - Serigrafía (80 x 60 cm.), 2013  *Buy Here*
(via gameroomrecordings)

iheartmyart:

Smithe, Lead Us - Serigrafía (80 x 60 cm.), 2013  *Buy Here*

(via gameroomrecordings)

(Source: smitheone)

bpod-mrc:

27 July 2014
Kettling Proteins
Prions are infectious proteins that can cause deadly diseases like bovine spongiform encephalopathy, or mad cow disease. They also infect yeast cells and this simple fungus has been found to produce a protein, Btn2, that targets prions and kettles them into a small area inside the cell, rather like the way riot police control an unruly crowd. When the cell divides, one of the two offspring is free from prions and can thrive. Intriguingly, Btn2 has similarities to human hook proteins, which play an important role in positioning components inside human cells so they can divide correctly. Pictured are three yeast colonies, the top right producing Btn2 and with mainly healthy cells (stained red) and some infected by prions (white). The lower colony is producing Cur1, a protein allied to Btn2 and has some healthy cells, while the top left colony is producing neither protein and is heavily infected.
Written by Mick Warwicker
—
Image by Reed Wickner and colleaguesNational Institutes of Health, USAOriginally published under a Creative Commons Licence (BY 4.0)Research published in PNAS, June 2014
—
You can also follow BPoD on Twitter and Facebook

bpod-mrc:

27 July 2014

Kettling Proteins

Prions are infectious proteins that can cause deadly diseases like bovine spongiform encephalopathy, or mad cow disease. They also infect yeast cells and this simple fungus has been found to produce a protein, Btn2, that targets prions and kettles them into a small area inside the cell, rather like the way riot police control an unruly crowd. When the cell divides, one of the two offspring is free from prions and can thrive. Intriguingly, Btn2 has similarities to human hook proteins, which play an important role in positioning components inside human cells so they can divide correctly. Pictured are three yeast colonies, the top right producing Btn2 and with mainly healthy cells (stained red) and some infected by prions (white). The lower colony is producing Cur1, a protein allied to Btn2 and has some healthy cells, while the top left colony is producing neither protein and is heavily infected.

Written by Mick Warwicker

Image by Reed Wickner and colleagues
National Institutes of Health, USA
Originally published under a Creative Commons Licence (BY 4.0)
Research published in PNAS, June 2014

You can also follow BPoD on Twitter and Facebook

gyclli:



Dawn in Bali ~ Blue beach, Indonesia
Dawn in Bali / Ko Zaw

gyclli:

Dawn in Bali ~ Blue beach, Indonesia

Dawn in Bali /

(via eswynn)

ifuckingloveminerals:

Segnitite
Clara Mine, Rankach valley, Oberwolfach, Wolfach, Black Forest, Baden-Württemberg, Germany

ifuckingloveminerals:

Segnitite

Clara Mine, Rankach valley, Oberwolfach, Wolfach, Black Forest, Baden-Württemberg, Germany

(via mushroooms)

neurosciencestuff:

(Image caption: Granule cells connect with other cells via long projections (dendrites). The actual junctions (synapses) are located on thorn-like protuberances called “spines”. Spines are shown in green in the computer reconstruction. Credit: DZNE/Michaela Müller)
A protein couple controls flow of information into the brain’s memory center
Neuroscientists in Bonn and Heidelberg have succeeded in providing new insights into how the brain works. Researchers at the DZNE and the German Cancer Research Center (DKFZ) analyzed tissue samples from mice to identify how two specific proteins, ‘CKAMP44’ and ‘TARP Gamma-8’, act upon the brain’s memory center. These molecules, which have similar counterparts in humans, affect the connections between nerve cells and influence the transmission of nerve signals into the hippocampus, an area of the brain that plays a significant role in learning processes and the creation of memories. The results of the study have been published in the journal Neuron.
Brain function depends on the active communication between nerve cells, known as neurons. For this purpose, neurons are woven together into a dense network where they constantly relay signals to one another. However, neurons do not form direct contacts with each other. Instead they are separated by an extremely narrow gap, known as the synapse. This gap is bridged by ‘neurotransmitters’, which carry nerve signals from one cell to the next.
Docking stations

Specific molecular complexes in the cell’s outer shell, so-called ‘receptors’, receive the signal by binding the neurotransmitters. This triggers an electrical impulse in the receptor-bearing cell and thus the nerve signal has moved on one neuron further.
In the current study, a team led by Dr Jakob von Engelhardt focused on the AMPA receptors. These bind the neurotransmitter glutamate and are particularly common in the brain. “We looked at AMPA receptors in an area of the brain, which constitutes the main entrance to the hippocampus,” explains von Engelhardt, who works for the DZNE and DKFZ. “The hippocampus is responsible for learning and memory formation. Among other things it processes and combines sensory perception. We therefore asked ourselves how the flow of information into the hippocampus is controlled.”
A pair of helpers
Dr von Engelhardt’s research team specifically focused on two protein molecules: ‘CKAMP44’ and ‘TARP Gamma-8’. These proteins are present, along with AMPA receptors, in the ‘granule’ cells, which are neurons that receive signals from areas outside of the hippocampus. It was already known that these proteins form protein complexes with AMPA receptors. “We have now found out that they exert a significant influence on the functioning of glutamate receptors. Each in its own way, as chemically they are completely different,” says the neuroscientist. “We identified that the ability of a nerve cell to receive signals doesn’t depend solely on the actual receptors; CKAMP44 and TARP Gamma-8 are just as important. Their function cannot be separated from that of the receptors.”
This was the result of an analysis in which the researchers compared brain tissue from mice with a natural genotype with brain tissue from genetically modified mice. Neurons in the genetically modified animals were not able to produce either CKAMP44 or TARP Gamma-8 or both.
Long-term effect
The researchers discovered, among other things, that both proteins promote the transportation of glutamate receptors to the cell surface. “This means they influence how receptive the nerve cell is to incoming signals,” says von Engelhardt.
However, the number of receptors and thus the signal reception can be altered by neuronal activity. The von Engelhardt group found that in this regard the auxiliary molecules have different effects: TARP Gamma-8 is essential to ensure that more AMPA receptors are integrated into the synapse following a plasticity induction protocol, whereas CKAMP44 plays no role in this context. “Synapses alter their communication depending on their activity. This ability is called plasticity. Some of the changes involved are only temporary, others may last longer,” explains von Engelhardt. “TARP Gamma-8 influences long-term plasticity. It makes the cell able to strengthen synaptic communication for a prolonged time-period. The larger the number of receptors on the receiving side of the synapse, the better the neuronal connection.”
The number of receptors doesn’t change suddenly, but remains largely stable for a certain amount of time. “This condition may last for hours, days or even longer. This long-term effect is essential for the creation of memories. We can only remember things if the connections between neurons undergo a long-lasting change,” says the scientist.
Fast sequence of signals
However, CKAMP44 and TARP Gamma-8 also act over shorter periods of time. The research team discovered that the molecules affect how quickly the AMPA receptors return to a receptive state. “If glutamate has docked on to a receptor, it takes a while until the receptor can react to the next neurotransmitter. CKAMP44 lengthens this period. In contrast, TARP Gamma-8 helps the receptor to recover more quickly,” says von Engelhardt.
Hence, CKAMP44 temporarily weakens the synaptic connection, while TARP Gamma-8 strengthens it. Through the interplay of these proteins the synapse is able to tune its sensitivity to a specific level. This condition can last from milliseconds to a few seconds before the strength of the connection is again adapted. Specialists refer to this as “short-term plasticity”.
“These molecules ultimately influence how well the nerve cell is able to react to a rapid succession of signals,” the scientist summarises the findings. “Such a rapid firing enables neuronal networks to synchronize their activity, which is a common process in the brain.”
Sensitive balance
Much to the researchers’ surprise, it turned out that the two proteins influence not only the synapse but also the shape of the nerve cells. In the absence of these auxiliary molecules, the neurons have fewer dendrites to establish contact with other nerve cells. “The organism can use CKAMP44 and TARP Gamma-8 molecules to regulate neuronal connections in a number of ways,” von Engelhardt says. “This ability depends on the balance between the partners, as to some extent they have a contrary effect. The way in which the neurons of the hippocampus react to signals from other regions of the brain is therefore highly dependent on the presence and the expression ratio of these molecules.”
Since the two molecules act directly on the structure and function of synapses of granule cells, Jakob von Engelhardt considers it probable that they also have an influence on learning and memory.

neurosciencestuff:

(Image caption: Granule cells connect with other cells via long projections (dendrites). The actual junctions (synapses) are located on thorn-like protuberances called “spines”. Spines are shown in green in the computer reconstruction. Credit: DZNE/Michaela Müller)

A protein couple controls flow of information into the brain’s memory center

Neuroscientists in Bonn and Heidelberg have succeeded in providing new insights into how the brain works. Researchers at the DZNE and the German Cancer Research Center (DKFZ) analyzed tissue samples from mice to identify how two specific proteins, ‘CKAMP44’ and ‘TARP Gamma-8’, act upon the brain’s memory center. These molecules, which have similar counterparts in humans, affect the connections between nerve cells and influence the transmission of nerve signals into the hippocampus, an area of the brain that plays a significant role in learning processes and the creation of memories. The results of the study have been published in the journal Neuron.

Brain function depends on the active communication between nerve cells, known as neurons. For this purpose, neurons are woven together into a dense network where they constantly relay signals to one another. However, neurons do not form direct contacts with each other. Instead they are separated by an extremely narrow gap, known as the synapse. This gap is bridged by ‘neurotransmitters’, which carry nerve signals from one cell to the next.

Docking stations

Specific molecular complexes in the cell’s outer shell, so-called ‘receptors’, receive the signal by binding the neurotransmitters. This triggers an electrical impulse in the receptor-bearing cell and thus the nerve signal has moved on one neuron further.

In the current study, a team led by Dr Jakob von Engelhardt focused on the AMPA receptors. These bind the neurotransmitter glutamate and are particularly common in the brain. “We looked at AMPA receptors in an area of the brain, which constitutes the main entrance to the hippocampus,” explains von Engelhardt, who works for the DZNE and DKFZ. “The hippocampus is responsible for learning and memory formation. Among other things it processes and combines sensory perception. We therefore asked ourselves how the flow of information into the hippocampus is controlled.”

A pair of helpers

Dr von Engelhardt’s research team specifically focused on two protein molecules: ‘CKAMP44’ and ‘TARP Gamma-8’. These proteins are present, along with AMPA receptors, in the ‘granule’ cells, which are neurons that receive signals from areas outside of the hippocampus. It was already known that these proteins form protein complexes with AMPA receptors. “We have now found out that they exert a significant influence on the functioning of glutamate receptors. Each in its own way, as chemically they are completely different,” says the neuroscientist. “We identified that the ability of a nerve cell to receive signals doesn’t depend solely on the actual receptors; CKAMP44 and TARP Gamma-8 are just as important. Their function cannot be separated from that of the receptors.”

This was the result of an analysis in which the researchers compared brain tissue from mice with a natural genotype with brain tissue from genetically modified mice. Neurons in the genetically modified animals were not able to produce either CKAMP44 or TARP Gamma-8 or both.

Long-term effect

The researchers discovered, among other things, that both proteins promote the transportation of glutamate receptors to the cell surface. “This means they influence how receptive the nerve cell is to incoming signals,” says von Engelhardt.

However, the number of receptors and thus the signal reception can be altered by neuronal activity. The von Engelhardt group found that in this regard the auxiliary molecules have different effects: TARP Gamma-8 is essential to ensure that more AMPA receptors are integrated into the synapse following a plasticity induction protocol, whereas CKAMP44 plays no role in this context. “Synapses alter their communication depending on their activity. This ability is called plasticity. Some of the changes involved are only temporary, others may last longer,” explains von Engelhardt. “TARP Gamma-8 influences long-term plasticity. It makes the cell able to strengthen synaptic communication for a prolonged time-period. The larger the number of receptors on the receiving side of the synapse, the better the neuronal connection.”

The number of receptors doesn’t change suddenly, but remains largely stable for a certain amount of time. “This condition may last for hours, days or even longer. This long-term effect is essential for the creation of memories. We can only remember things if the connections between neurons undergo a long-lasting change,” says the scientist.

Fast sequence of signals

However, CKAMP44 and TARP Gamma-8 also act over shorter periods of time. The research team discovered that the molecules affect how quickly the AMPA receptors return to a receptive state. “If glutamate has docked on to a receptor, it takes a while until the receptor can react to the next neurotransmitter. CKAMP44 lengthens this period. In contrast, TARP Gamma-8 helps the receptor to recover more quickly,” says von Engelhardt.

Hence, CKAMP44 temporarily weakens the synaptic connection, while TARP Gamma-8 strengthens it. Through the interplay of these proteins the synapse is able to tune its sensitivity to a specific level. This condition can last from milliseconds to a few seconds before the strength of the connection is again adapted. Specialists refer to this as “short-term plasticity”.

“These molecules ultimately influence how well the nerve cell is able to react to a rapid succession of signals,” the scientist summarises the findings. “Such a rapid firing enables neuronal networks to synchronize their activity, which is a common process in the brain.”

Sensitive balance

Much to the researchers’ surprise, it turned out that the two proteins influence not only the synapse but also the shape of the nerve cells. In the absence of these auxiliary molecules, the neurons have fewer dendrites to establish contact with other nerve cells. “The organism can use CKAMP44 and TARP Gamma-8 molecules to regulate neuronal connections in a number of ways,” von Engelhardt says. “This ability depends on the balance between the partners, as to some extent they have a contrary effect. The way in which the neurons of the hippocampus react to signals from other regions of the brain is therefore highly dependent on the presence and the expression ratio of these molecules.”

Since the two molecules act directly on the structure and function of synapses of granule cells, Jakob von Engelhardt considers it probable that they also have an influence on learning and memory.

(Source: heroingranola)

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