Eek!
The current, on-going Ebola crisis is just the latest reminder that we live in a world dominated by microbes, many of them harmful to our health and lives.
The Ebola virus is indisputably frightening, with outbreaks that have a case fatality rate of up to 90 percent. Fortunately, its mode of transmission appears limited: Close contact with the blood, secretions, organs and other bodily fluids of infected animals. So far, its spread has been limited to defined regions of Africa where healthcare services and disease prevention efforts have proved minimal to non-existent.
For the time being, at least, Ebola seems a bit exotic. But there are plenty of menacing microbes closer at hand. They may not possess the same nasty ability to kill but they are often easier to transmit and more prone to infect.
Among them is Escherichia coli, more commonly called E. coli. It is an abundant bacterium. Most strains, which reside in the lower intestine of warm-blooded organisms (including humans) are harmless, but some strains are not. When the latter taint foods, perhaps through unseen and unknown fecal contamination, the result can be severe food poisoning or worse. 
E. coli outbreaks are not uncommon. They can – and do – kill too.
That’s worth remembering, along with these rules.
Pictured: Electron micrograph of E. coli bacteria courtesy of Thomas Deerinck, National Center for Microscopy and Imaging Research at UC San Diego.

Eek!

The current, on-going Ebola crisis is just the latest reminder that we live in a world dominated by microbes, many of them harmful to our health and lives.

The Ebola virus is indisputably frightening, with outbreaks that have a case fatality rate of up to 90 percent. Fortunately, its mode of transmission appears limited: Close contact with the blood, secretions, organs and other bodily fluids of infected animals. So far, its spread has been limited to defined regions of Africa where healthcare services and disease prevention efforts have proved minimal to non-existent.

For the time being, at least, Ebola seems a bit exotic. But there are plenty of menacing microbes closer at hand. They may not possess the same nasty ability to kill but they are often easier to transmit and more prone to infect.

Among them is Escherichia coli, more commonly called E. coli. It is an abundant bacterium. Most strains, which reside in the lower intestine of warm-blooded organisms (including humans) are harmless, but some strains are not. When the latter taint foods, perhaps through unseen and unknown fecal contamination, the result can be severe food poisoning or worse

E. coli outbreaks are not uncommon. They can – and do – kill too.

That’s worth remembering, along with these rules.

Pictured: Electron micrograph of E. coli bacteria courtesy of Thomas Deerinck, National Center for Microscopy and Imaging Research at UC San Diego.

In Rats and Men, Nicotine Withdrawal Casts Similar PallReduced reward response in brains helps explain why it’s so hard to quit smoking
Efforts to quit smoking tend to end in failure. Almost half of smokers attempt to quit each year, but only 4 to 7 percent succeed on any given attempt without medicines or assistance, according to the American Cancer Society, and less than 25 percent of smokers who use medicines remain smoke-free for more than six months. Relapse is especially common within 48 hours of quitting when nicotine withdrawal symptoms are most acute.
In a set of novel experiments involving both humans and rats, researchers at the University of California, San Diego School of Medicine, Florida Atlantic University (FAU), University of Pittsburgh, Washington University and Harvard Medical School report that the brain’s response to reward – its ability to recognize and derive pleasure from natural stimuli such as food, money or sex – is measurably reduced after nicotine withdrawal.
The findings, published this week online in JAMA Psychiatry, suggest that nicotine withdrawal significantly impacts the ability to modulate behavioral choices based on the expectancy of reward. This deficit is seen often in people who suffer from depression.
“What we saw in both humans and rats was decreased responsiveness to reward,” said Athina Markou, PhD, professor and vice-chair of research in the Department of Psychiatry at UC San Diego. “During acute nicotine withdrawal, both people and animals attended less to positive rewards. That’s a hallmark of depression. And there is evidence that people who already express depressive symptoms and quit smoking are more likely to become clinically depressed and stay that way. These findings have an obvious bearing on how we approach cessation treatment.” 
The study authors say the breadth of the findings involving similar results in two different species offer a strong translational framework for future studies that will allow development of clinical treatments focusing on reward responsiveness during early nicotine withdrawal.
“The fact that the effect was similar across species using this translational task not only provides us with a ready framework to proceed with additional research to better understand the mechanisms underlying withdrawal of nicotine, and potentially new treatment development, but it also makes us feel more confident that we are actually studying the same behavior in humans and rats as the studies move forward,” said Michele Pergadia, PhD, associate professor of clinical biomedical science in the Charles E. Schmidt College of Medicine at FAU. 
The experiments reported in JAMA Psychiatry assessed reward responsiveness based upon the propensity to modulate behavior according to prior experience. In human testing, conducted at Washington University, participants were asked to repeat a computer task, with “correct” responses earning a modest financial reward. In testing at UC San Diego, rats were trained to press a lever upon hearing a specific tone to earn a food reward.
Results were similar. Human participants who were smokers but who had abstained from smoking for 24 hours prior to testing and rats chronically exposed to nicotine but deprived for 24 hours also prior to testing both performed less effectively than non-smokers and rats with no nicotine experience. That is, both humans and rats withdrawing from nicotine failed to display a bias toward maximizing their rewards. 
Markou’s team, which included co-authors Andre Der-Avakian, PhD, and Manoranjan D’Souza, MD, PhD, subsequently re-exposed rats to nicotine and re-tested them. This time, the animals showed a heightened reward response, stronger than before.
“This finding indicates that after the initial withdrawal, if a relapse occurs, it will produce a more pleasurable effect. That’s why smokers who have a single cigarette after quitting often find it triggers a full relapse and they’re soon back to smoking as much as before.”
Markou and Pergadia say the findings open up two avenues of future research: Studying the neurobiology of the reward response phenomenon to pinpoint where in the brain it occurs and which circuits or neurons are involved; and assessing potential medications on rats during reward response testing. Promising drugs, if approved by the FDA for human administration, could then be tested on humans in similar experiments – an approach that could provide both new insights and speed the drug development process.

In Rats and Men, Nicotine Withdrawal Casts Similar Pall
Reduced reward response in brains helps explain why it’s so hard to quit smoking

Efforts to quit smoking tend to end in failure. Almost half of smokers attempt to quit each year, but only 4 to 7 percent succeed on any given attempt without medicines or assistance, according to the American Cancer Society, and less than 25 percent of smokers who use medicines remain smoke-free for more than six months. Relapse is especially common within 48 hours of quitting when nicotine withdrawal symptoms are most acute.

In a set of novel experiments involving both humans and rats, researchers at the University of California, San Diego School of Medicine, Florida Atlantic University (FAU), University of Pittsburgh, Washington University and Harvard Medical School report that the brain’s response to reward – its ability to recognize and derive pleasure from natural stimuli such as food, money or sex – is measurably reduced after nicotine withdrawal.

The findings, published this week online in JAMA Psychiatry, suggest that nicotine withdrawal significantly impacts the ability to modulate behavioral choices based on the expectancy of reward. This deficit is seen often in people who suffer from depression.

“What we saw in both humans and rats was decreased responsiveness to reward,” said Athina Markou, PhD, professor and vice-chair of research in the Department of Psychiatry at UC San Diego. “During acute nicotine withdrawal, both people and animals attended less to positive rewards. That’s a hallmark of depression. And there is evidence that people who already express depressive symptoms and quit smoking are more likely to become clinically depressed and stay that way. These findings have an obvious bearing on how we approach cessation treatment.” 

The study authors say the breadth of the findings involving similar results in two different species offer a strong translational framework for future studies that will allow development of clinical treatments focusing on reward responsiveness during early nicotine withdrawal.

“The fact that the effect was similar across species using this translational task not only provides us with a ready framework to proceed with additional research to better understand the mechanisms underlying withdrawal of nicotine, and potentially new treatment development, but it also makes us feel more confident that we are actually studying the same behavior in humans and rats as the studies move forward,” said Michele Pergadia, PhD, associate professor of clinical biomedical science in the Charles E. Schmidt College of Medicine at FAU. 

The experiments reported in JAMA Psychiatry assessed reward responsiveness based upon the propensity to modulate behavior according to prior experience. In human testing, conducted at Washington University, participants were asked to repeat a computer task, with “correct” responses earning a modest financial reward. In testing at UC San Diego, rats were trained to press a lever upon hearing a specific tone to earn a food reward.

Results were similar. Human participants who were smokers but who had abstained from smoking for 24 hours prior to testing and rats chronically exposed to nicotine but deprived for 24 hours also prior to testing both performed less effectively than non-smokers and rats with no nicotine experience. That is, both humans and rats withdrawing from nicotine failed to display a bias toward maximizing their rewards. 

Markou’s team, which included co-authors Andre Der-Avakian, PhD, and Manoranjan D’Souza, MD, PhD, subsequently re-exposed rats to nicotine and re-tested them. This time, the animals showed a heightened reward response, stronger than before.

“This finding indicates that after the initial withdrawal, if a relapse occurs, it will produce a more pleasurable effect. That’s why smokers who have a single cigarette after quitting often find it triggers a full relapse and they’re soon back to smoking as much as before.”

Markou and Pergadia say the findings open up two avenues of future research: Studying the neurobiology of the reward response phenomenon to pinpoint where in the brain it occurs and which circuits or neurons are involved; and assessing potential medications on rats during reward response testing. Promising drugs, if approved by the FDA for human administration, could then be tested on humans in similar experiments – an approach that could provide both new insights and speed the drug development process.

Scientists Discover Neurochemical Imbalance in Schizophrenia
Using human induced pluripotent stem cells (hiPSCs), researchers at Skaggs School of Pharmacy and Pharmaceutical Sciences at University of California, San Diego have discovered that neurons from patients with schizophrenia secrete higher amounts of three neurotransmitters broadly implicated in a range of psychiatric disorders.
The findings, reported online Sept. 11 in Stem Cell Reports, represent an important step toward understanding the chemical basis for schizophrenia, a chronic, severe and disabling brain disorder that affects an estimated one in 100 persons at some point in their lives. Currently, schizophrenia has no known definitive cause or cure and leaves no tell-tale physical marks in brain tissue.
"The study provides new insights into neurotransmitter mechanisms in schizophrenia that can lead to new drug targets and therapeutics,” said senior author Vivian Hook, PhD, a professor with Skaggs School of Pharmacy and UC San Diego School of Medicine.
In the study, UC San Diego researchers with colleagues at The Salk Institute for Biological Studies and the Icahn School of Medicine at Mount Sinai, N.Y., created functioning neurons derived from hiPSCs, themselves reprogrammed from skin cells of schizophrenia patients. The approach allowed scientists to observe and stimulate human neurons in ways impossible in animal models or human subjects.
Researchers activated these neurons so that they would secrete neurotransmitters – chemicals that excite or inhibit the transmission of electrical signals through the brain. The process was replicated on stem cell lines from healthy adults.
A comparison of neurotransmitters produced by the cultured “brain in a dish” neurons showed that the neurons derived from schizophrenia patients secreted significantly greater amounts of the catecholamine neurotransmitters dopamine, norepinephrine and epinephrine.
Catecholamine neurotransmitters are synthesized from the amino acid tyrosine and the regulation of these neurotransmitters is known to be altered in a variety of psychiatric diseases. Several psychotropic drugs selectively target the activity of these neurotransmitters in the brain.
In addition to documenting aberrant neurotransmitter secretion from neurons derived from patients with schizophrenia, researchers also observed that more neurons were dedicated to the production of tyrosine hydroxylase, the first enzyme in the biosynthetic pathway for the synthesis of dopamine, from which both norepinephrine and epinephrine are made.
This discovery is significant because it offers a reason for why schizophrenia patients have altered catecholamine neurotransmitter levels: They are preprogrammed to have more of the neurons that make these neurotransmitters.
“All behavior has a neurochemical basis in the brain,” Hook said. “This study shows that it is possible to look at precise chemical changes in neurons of people with schizophrenia.”
The applications for future treatments include being able to evaluate the severity of an individual’s disease, identify different sub-types of the disease and pre-screen patients for drugs that would be most likely to help them. It also offers a way to test the efficacy of new drugs.
“It is very powerful to be able to see differences in neurons derived from individual patients and a big accomplishment in the field to develop a method that allows this,” Hook said.
Pictured: Enzymes that biosynthesize the neurotransmitters dopamine (left), norepinephrine (center) and epinephrine (right).

Scientists Discover Neurochemical Imbalance in Schizophrenia

Using human induced pluripotent stem cells (hiPSCs), researchers at Skaggs School of Pharmacy and Pharmaceutical Sciences at University of California, San Diego have discovered that neurons from patients with schizophrenia secrete higher amounts of three neurotransmitters broadly implicated in a range of psychiatric disorders.

The findings, reported online Sept. 11 in Stem Cell Reports, represent an important step toward understanding the chemical basis for schizophrenia, a chronic, severe and disabling brain disorder that affects an estimated one in 100 persons at some point in their lives. Currently, schizophrenia has no known definitive cause or cure and leaves no tell-tale physical marks in brain tissue.

"The study provides new insights into neurotransmitter mechanisms in schizophrenia that can lead to new drug targets and therapeutics,” said senior author Vivian Hook, PhD, a professor with Skaggs School of Pharmacy and UC San Diego School of Medicine.

In the study, UC San Diego researchers with colleagues at The Salk Institute for Biological Studies and the Icahn School of Medicine at Mount Sinai, N.Y., created functioning neurons derived from hiPSCs, themselves reprogrammed from skin cells of schizophrenia patients. The approach allowed scientists to observe and stimulate human neurons in ways impossible in animal models or human subjects.

Researchers activated these neurons so that they would secrete neurotransmitters – chemicals that excite or inhibit the transmission of electrical signals through the brain. The process was replicated on stem cell lines from healthy adults.

A comparison of neurotransmitters produced by the cultured “brain in a dish” neurons showed that the neurons derived from schizophrenia patients secreted significantly greater amounts of the catecholamine neurotransmitters dopamine, norepinephrine and epinephrine.

Catecholamine neurotransmitters are synthesized from the amino acid tyrosine and the regulation of these neurotransmitters is known to be altered in a variety of psychiatric diseases. Several psychotropic drugs selectively target the activity of these neurotransmitters in the brain.

In addition to documenting aberrant neurotransmitter secretion from neurons derived from patients with schizophrenia, researchers also observed that more neurons were dedicated to the production of tyrosine hydroxylase, the first enzyme in the biosynthetic pathway for the synthesis of dopamine, from which both norepinephrine and epinephrine are made.

This discovery is significant because it offers a reason for why schizophrenia patients have altered catecholamine neurotransmitter levels: They are preprogrammed to have more of the neurons that make these neurotransmitters.

“All behavior has a neurochemical basis in the brain,” Hook said. “This study shows that it is possible to look at precise chemical changes in neurons of people with schizophrenia.”

The applications for future treatments include being able to evaluate the severity of an individual’s disease, identify different sub-types of the disease and pre-screen patients for drugs that would be most likely to help them. It also offers a way to test the efficacy of new drugs.

“It is very powerful to be able to see differences in neurons derived from individual patients and a big accomplishment in the field to develop a method that allows this,” Hook said.

Pictured: Enzymes that biosynthesize the neurotransmitters dopamine (left), norepinephrine (center) and epinephrine (right).

River of Dreams
The cortex is the brain’s outermost layer, visually characterized by its notable sulci or deep folds, which allow the brain to cram more neurons into limited space. When you look at a human brain, you see only about one-third of its surface, the other two-thirds are hidden in the folds. The more wrinkly the brain surface, the greater the ability to think, generally speaking. 
The cortex is where much of our brain’s higher executive functions occur, from interpreting sensory input and controlling voluntary movement to generating thoughts and forming memories. Naturally, doing all of that work requires a large and steady supply of oxygen and other nutrients.
Above is wide-field confocal micrograph by Tom Deerinck at the National Center for Microscopy Imaging and Research at UC San Diego. The image depicts the in situ superficial vasculature (blood vessels) of a rat cerebral cortex, whose brains are very similar to humans in basic structure and function. It was made using 50 optical sections.

River of Dreams

The cortex is the brain’s outermost layer, visually characterized by its notable sulci or deep folds, which allow the brain to cram more neurons into limited space. When you look at a human brain, you see only about one-third of its surface, the other two-thirds are hidden in the folds. The more wrinkly the brain surface, the greater the ability to think, generally speaking. 

The cortex is where much of our brain’s higher executive functions occur, from interpreting sensory input and controlling voluntary movement to generating thoughts and forming memories. Naturally, doing all of that work requires a large and steady supply of oxygen and other nutrients.

Above is wide-field confocal micrograph by Tom Deerinck at the National Center for Microscopy Imaging and Research at UC San Diego. The image depicts the in situ superficial vasculature (blood vessels) of a rat cerebral cortex, whose brains are very similar to humans in basic structure and function. It was made using 50 optical sections.

Local Bars and Restaurants Urge Pregnant Women Not to Drink
All things in moderation, the saying goes, but if you are a pregnant woman no amount of alcohol is known to be safe for the developing baby.
“When a pregnant woman drinks alcohol so does her baby,” said Kenneth Lyons Jones, MD, chief of the Division of Dysmorphology and Teratology in the Department of Pediatrics at University of California, San Diego School of Medicine. “So why take the risk?”
To help get the word out that alcohol and pregnancy don’t mix, volunteers with the Southern California affiliate of the National Organization on Fetal Alcohol Syndrome (SoCal NOFAS) are handing out “Pregnant? Don’t Drink” coasters to San Diego area bars and restaurants on Tuesday, September 9th as part of International Fetal Alcohol Spectrum Disorders (FASD) Awareness Day.
International FASD Awareness Day is held annually on the ninth day of the ninth month to urge women not to drink during the full nine months of pregnancy.
Read more here

Local Bars and Restaurants Urge Pregnant Women Not to Drink

All things in moderation, the saying goes, but if you are a pregnant woman no amount of alcohol is known to be safe for the developing baby.

“When a pregnant woman drinks alcohol so does her baby,” said Kenneth Lyons Jones, MD, chief of the Division of Dysmorphology and Teratology in the Department of Pediatrics at University of California, San Diego School of Medicine. “So why take the risk?”

To help get the word out that alcohol and pregnancy don’t mix, volunteers with the Southern California affiliate of the National Organization on Fetal Alcohol Syndrome (SoCal NOFAS) are handing out “Pregnant? Don’t Drink” coasters to San Diego area bars and restaurants on Tuesday, September 9th as part of International Fetal Alcohol Spectrum Disorders (FASD) Awareness Day.

International FASD Awareness Day is held annually on the ninth day of the ninth month to urge women not to drink during the full nine months of pregnancy.

Read more here

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