Revolution or Heroin

Un blog enfocado a todas esas grandes cosas que conforman la vida. http://regretloversguiltdreams.tumblr.com/

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Glow Pro

The springtail – a mini arthropod that's easy to nurture in the laboratory – produces bioluminescence (light-emission) using a novel molecular system. This finding could help advance biomedical research applications – commonly used to highlight or report production of molecules – that rely on glow-in-the-dark chemicals

Read the published research article here

Image from work by Manabu Bessho-Uehara and colleagues

The Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Sendai, Japan

Image contributed by the authors under a Creative Commons Attribution 4.0 International (CC BY 4.0) licence

Published in Biology Open, May 2025

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[bogleech]

I just found out through @revretch​ about needlenose flies!? They’re horseflies, so the males feed on nectar while the females feed on both nectar and blood, but they both have this huge long “proboscis” for drinking nectar out of deeper flowers, like a hummingbird! That’s completely useless for biting, but insects have multiple pairs of mouthparts anyway. So one pair forms the nectar feeding tube, while another pair form the usual short blades, under the head, that a horsefly drinks blood with. It’s all one mouth, but it’s like if your upper jaw was stretched into a straw. The EFFECT is like two different mouths for two different purposes!

[neurosciencestuff]

Sleep Phase Can Reduce Anxiety in People with PTSD

A new study shows that sleep spindles, brief bursts of brain activity occurring during one phase of sleep and captured by EEG, may regulate anxiety in people with post-traumatic stress disorder (PTSD).

The study shines a light on the role of spindles in alleviating anxiety in PTSD as well as confirms their established role in the transfer of new information to longer-term memory storage. The findings challenge recent work by other researchers that has indicated spindles may heighten intrusive and violent thoughts in people with PTSD.

The final draft of the preprint publishes in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging on May 3, 2023.

“These findings may be meaningful not only for people with PTSD, but possibly for those with anxiety disorders,” said senior author Anne Richards, MD, MPH, of the UCSF Department of Psychiatry and Behavioral Sciences, the Weill Institute for Neurosciences and the San Francisco VA Medical Center. “There are non-invasive ways that might harness the benefits of this sleep stage to provide relief from symptoms."

The researchers enrolled 45 participants who had all experienced combat or noncombat trauma; approximately half had moderate symptoms of PTSD and the other half had milder symptoms or were asymptomatic. The researchers studied the spindles during non-rapid eye movement 2 (NREM2) sleep, the phase of sleep when they mainly occur, which comprises about 50% of total sleep.

Violent Images Used to Test Brain Processing

In the study, participants attended a “stress visit” in which they were shown images of violent scenes, such as accidents, war violence, and human and animal injury or mutilation, prior to a lab-monitored nap that took place about two hours later.

Anxiety surveys were conducted immediately after exposure to the images as well as after the nap when recall of the images was tested. The researchers also compared anxiety levels in the stress visit to those in a control visit without exposure to these images.

The researchers found that spindle rate frequency was higher during the stress visit than during the control visit. “This provides compelling evidence that stress was a contributing factor in spindle-specific sleep rhythm changes,” said first author Nikhilesh Natraj, PhD, of the UCSF Department of Neurology, the Weill Institute for Neurosciences and the San Francisco VA Medical Center. Notably, in participants with greater PTSD symptoms, the increased spindle frequency after stress exposure reduced anxiety post-nap.

Sleeping Meds, Electrical Stimulation May Promote Sleep Spindles

In the study, naps took place shortly after exposure to violent images – raising a question about whether sleep occurring days or weeks after trauma will have the same therapeutic effect. The researchers think this is likely, and point to interventions that could trigger the spindles associated with NREM2 sleep and benefit patients with stress and anxiety disorders.

Prescription drugs, like Ambien, are one option that should be studied further, “but a big question is whether the spindles induced by medications can also bring about the full set of brain processes associated with naturally occurring spindles,” said Richards.

Electrical brain stimulation is another area for more study, researchers said. “Transcranial electrical stimulation in which small currents are passed through the scalp to boost spindle rhythms or so-called targeted memory reactivation, which involves a cue, like an odor or sound used during an experimental session and replayed during sleep may also induce spindles,” said Natraj.

“In lieu of such inventions, sleep hygiene is definitely a zero-cost and easy way to ensure we are entering sleep phases in an appropriate fashion, thereby maximizing the benefit of spindles in the immediate aftermath of a stressful episode,” he said.

The researchers’ next project is to study the role of spindles in the consolidation and replay of intrusive and violent memories many weeks after trauma exposure.

[neurosciencestuff]

Astrocyte cells critical for learning skilled movements

When astrocyte function is disrupted, neurons in the brain’s motor cortex struggle to execute and refine motion, a new study in mice shows.

From steering a car to swinging a tennis racket, we learn to execute all kinds of skilled movements during our lives. You might think this learning is only implemented by neurons, but a new study by researchers at The Picower Institute for Learning and Memory at MIT shows the essential role of another brain cell type: astrocytes.

Just as teams of elite athletes train alongside staffs of coaches, ensembles of neurons in the brain’s motor cortex depend on nearby astrocytes to help them learn to encode when and how to move, and the optimal timing and trajectory of a motion, the study shows. Describing a series of experiments in mice, the new paper in the Journal of Neuroscience reveals two specific ways that astrocytes directly impact motor learning, maintaining an optimal molecular balance in which the neuronal ensembles can properly refine movement performance.

“This finding is part of a body of work from our lab and other labs that elevate the importance of astrocytes to neuronal encoding and hence to behavior,” said senior author Mriganka Sur, Newton Professor of Neuroscience in The Picower Institute and MIT’s Department of Brain and Cognitive Sciences. “This shows that while the population coding of behaviors is a neuronal function, we need to include astrocytes as partners with them.”

Picower Institute Postdoc Jennifer Shih and former Sur Lab postdocs Chloe Delepine and Keji Li are the paper’s co-lead authors.

“This research highlights the complexity of astrocytes and the importance of astrocyte-neuron interactions in fine-tuning brain function by providing concrete evidence of these mechanisms in the motor cortex,” Delepine said.

Messing with motor mastery

The team gave their mice a simple motor task to master. When cued with a tone, the mice had to reach for and push down a lever within five seconds. The rodents showed they could learn the task over a few days and master it within a couple of weeks. They not only performed the task more accurately, but also their reactions quickened and the trajectory of their reaching and pushing became smoother and more uniform.

In some of the mice, however, the team employed precision molecular interventions to disrupt two specific functions of astrocytes in the motor cortex. In some mice, they disrupted the astrocytes’ ability to soak up the neurotransmitter glutamate, a chemical that excites neural activity when it is received at connections called synapses. In other mice they hyperactivated the astrocytes’ calcium signals, which affected how they function. In both ways, the interventions disrupted the normal process by which neurons would form or change their connections with each other, a process called “plasticity” that enables learning.

The interventions each affected the performance of the mice. The first one (a knockdown of the glutamate transporter GLT1) didn’t affect whether the mice pushed the lever or how quickly they did so. Instead it disrupted the smoothness of the motion. Mice with GLT1 disrupted remained erratic and shaky, as if unable to refine their technique. Mice subjected to the second intervention (activation of Gq signaling) showed deficits not only in the smoothness of their motion trajectory but also in their understanding of when to push the lever and their quickness in doing so.

The team dug deeper into how these deficits emerged. Using a two-photon microscope they tracked neural activity in the motor cortex in unaltered mice and mice treated with each intervention. Compared to what they saw in normal mice, the mice with GLT1 disrupted showed less correlated activity among neurons. Mice with Gq activation showed excessive correlated activity compared to the normal mice.

“The data suggest that an optimal level of neuronal correlation is required for the emergence of functional neuronal ensembles that drive task performance,” the authors wrote. “Meaningful correlations that carry information are what drive motor learning rather than the absolute magnitude of potentially non-specific correlations.”

The team dug even deeper still. They carefully isolated astrocytes from the motor cortex of mice, including some who were untrained in the motor task as well as ones who were trained, including mice who were unaltered and mice who underwent each intervention. In all these samples of purified astrocytes, they then sequenced RNA to assess how they differed in their expression of genes. They found that in trained vs. untrained mice, astrocytes exhibited greater expression of genes related to GLT1. In mice where they intervened they saw lowered expression. That evidence further suggested that the glutamate transporter process is indeed fundamental to training in motor tasks.

“Here we show that astrocytes have an important role in enabling neurons to encode information properly, both the learning and the execution of a movement for example,” Sur said.

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Monocyte, Microlith, Mineral?

Every breath can be a struggle if you have the rare lung disease pulmonary alveolar microlithiasis. It’s caused by a faulty protein in the membranes of cells that line alveoli, tiny air sacs that fill your lungs. This causes mineral structures called hydroxyapatite microliths to form inside alveoli. Researchers now investigate this process by analysing RNA – a marker for gene activity – in lung tissue from human patients and a mouse model of the disease. Looking at immune cells called monocytes, which can develop into bone-degrading cells called osteoclasts, the team found that osteoclast-related genes were activated in alveolar monocytes. They also found that microliths, pictured using scanning electron microscopy at different resolutions in human (top) and mouse (bottom) lung tissue, contained osteoclast enzymes. This suggests that in response to microliths forming, osteoclast-like cells kickstart into action. This may present a new research avenue for pulmonary alveolar microlithiasis therapies.

Written by Lux Fatimathas

Image adapted from work by Yasuaki Uehara and colleagues

Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Nature Communications, March 2023

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Light-activated Bacteria

Neuroscientists have had the monopoly on using light-activated proteins to induce electrical impulses in cells. This ability to control cell firing at the flick of a switch has revolutionised research into the brain, but brain cells are not the only electrical cells in nature. It’s understood, for example, that changes in microbial cell electrophysiology regulate all sorts of processes including spore production, biofilm formation and susceptibility to antibiotics. With this in mind, researchers have now adapted tools previously used in neurons for use in bacteria. The bacteria in the video contain such photoswitch proteins and, when exposed to light for 10 seconds (every 10 minutes), become negatively charged (hyperpolarised) – seen as a pulse of blue colour. As a proof-of-concept experiment, these flashing bacteria open the door for research into various aspects of microbial electrophysiology and pave the way for developing synthetic bacteria whose functions can be controlled by light.

Written by Ruth Williams

Video from work by Tailise Carolina De Souza-Guerreiro and colleagues

School of Life Sciences, University of Warwick, Coventry, UK and Center for Nanoscience and Technology, Istituto Italiano di Teconologia, Milano, Italy

Video originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Advanced Science, January 2023

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[neurosciencestuff]

(Image caption: A microglial nodule, a dense collection of activated microglia, in the brainstem of a COVID-19 patient. The microglia, stained brown, are adjacent to two neurons (*). Photo courtesy of Dritan Agalliu and Michael Glendinning, Departments of Neurology and Pathology & Cell Biology at Columbia University Vagelos College of Physicians and Surgeons)

Coronavirus Does Not Infect the Brain But Still Inflicts Damage

SARS-CoV-2, the virus that causes COVID-19, likely does not directly infect the brain but can still inflict significant neurological damage, according to a new study from neuropathologists, neurologists, and neuroradiologists at Columbia University Vagelos College of Physicians and Surgeons.

“There’s been considerable debate about whether this virus infects the brain, but we were unable to find any signs of virus inside brain cells of more than 40 COVID-19 patients,” says James E. Goldman, MD, PhD, professor of pathology & cell biology (in psychiatry), who led the study with Peter D. Canoll, MD, PhD, professor of pathology & cell biology, and Kiran T. Thakur, MD, the Winifred Mercer Pitkin Assistant Professor of Neurology.

“At the same time, we observed many pathological changes in these brains, which could explain why severely ill patients experience confusion and delirium and other serious neurological effects—and why those with mild cases may experience ‘brain fog’ for weeks and months.”

The study, the largest and most detailed COVID-19 brain autopsy report published to date, suggests that the neurological changes often seen in these patients may result from inflammation triggered by the virus in other parts of the body or in the brain’s blood vessels.

The study was published in the journal Brain.

No virus in brain cells

The study examined the brains of 41 patients with COVID-19 who succumbed to the disease during their hospitalization. The patients ranged in age from 38 to 97; about half had been intubated and all had lung damage caused by the virus. Many of the patients were of Hispanic ethnicity. There was a wide range of hospital length with some patients dying soon after arrival to the emergency room while others remained in the hospital for months. All of the patients had extensive clinical and laboratory investigations, and some had brain MRI and CT scans.

To detect any virus in the neurons and glia cells of the brain, the researchers used multiple methods including RNA in situ hybridization, which can detect viral RNA within intact cells; antibodies that can detect viral proteins within cells; and RT-PCR, a sensitive technique for detecting viral RNA.

Despite their intensive search, the researchers found no evidence of the virus in the patients’ brain cells. Though they did detect very low levels of viral RNA by RT-PCR, this was likely due to virus in blood vessels or leptomeninges covering the brain.

“We’ve looked at more brains than other studies, and we’ve used more techniques to search for the virus. The bottom line is that we find no evidence of viral RNA or protein in brain cells,” Goldman says. “Though there are some papers that claim to have found virus in neurons or glia, we think that those result from contamination, and any virus in the brain is contained within the brain’s blood vessels.”

“If there’s any virus present in the brain tissue, it has to be in very small amounts and does not correlate with the distribution or abundance of neuropathological findings,” Canoll says.

The tests were conducted on more than two dozen brain regions, including the olfactory bulb, which was searched because some reports have speculated that the coronavirus can travel from the nasal cavity into the brain via the olfactory nerve. “Even there, we didn’t find any viral protein or RNA,” Goldman says, “though we found viral RNA and protein in the patients’ nasal mucosa and in the olfactory mucosa high in the nasal cavity.” (The latter finding appears in an unpublished study, currently on BioRxiv, led by Jonathan Overdevest, MD, PhD, assistant professor of otolaryngology, and Stavros Lomvardas, PhD, professor of biochemistry & molecular biophysics and neuroscience.)

Hypoxic damage and signs of neuronal death

Despite the absence of virus in the brain, in every patient the researchers found significant brain pathology, which mostly fell into two categories.

“The first thing we noticed was a lot of areas with damage from a lack of oxygen,” Goldman says. “They all had severe lung disease, so it’s not surprising that there’s hypoxic damage in the brain.”

Some of these were large areas caused by strokes, but most were very small and only detectable with a microscope. Based on other features, the researchers believe these small areas of hypoxic damage were caused by blood clots, common in patients with severe COVID-19, that temporarily stopped the supply of oxygen to that area.

A more surprising finding, Goldman says, was the large number of activated microglia they found in the brains of most patients. Microglia are immune cells that reside in the brain and can be activated by pathogens.

“We found clusters of microglia attacking neurons, a process called ‘neuronophagia,’” says Canoll. Since no virus was found in the brain, it’s possible the microglia may have been activated by inflammatory cytokines, such as Interleukin-6, associated with SARS-CoV-2 infection.

“At the same time, hypoxia can induce the expression of 'eat me' signals on the surface of neurons, making hypoxic neurons more vulnerable to activated microglia,” Canoll says, “so even without directly infecting brain cells, COVID-19 can cause damage to the brain.”

The group found this pattern of pathology in one of their first autopsies, described by Osama Al-Dalahmah, MD, PhD, instructor in pathology & cell biology, in a case report published last March. Over the next few months, as the neuropathologists did many more COVID brain autopsies, they saw similar findings over and over again and realized that this is a prominent and common neuropathological finding in patients who die of COVID.

The activated microglia were found predominantly in the lower brain stem, which regulates heart and breathing rhythms, as well as levels of consciousness, and in the hippocampus, which is involved in memory and mood.

“We know the microglia activity will lead to loss of neurons, and that loss is permanent,” Goldman says. “Is there enough loss of neurons in the hippocampus to cause memory problems? Or in other parts of the brain that help direct our attention? It’s possible, but we really don’t know at this point.”

Persistent neurological problems in survivors

Goldman says that more research is needed to understand the reasons why some post-COVID-19 patients continue to experience symptoms.

The researchers are now examining autopsies on patients who died several months after recovering from COVID-19 to learn more.

They are also examining the brains from patients who were critically ill with acute respiratory distress syndrome (ARDS) before the COVID-19 pandemic to see how much of COVID-19 brain pathology is a result of the severe lung disease.

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Halting Diabetes Destruction

Type 1 diabetes occurs when the body’s immune system attacks its own pancreatic islet cells – specifically the beta cells, which produce insulin. The pancreatic islets of mice with a version of type 1 diabetes are shown above. On the left, the animal’s T cells can be seen crowding into the islet to destroy the beta cells, while on the right far fewer T cells are present. That’s because the animal on the right had been receiving daily injections of a recently discovered mitochondrial protein called MOTS-c, which possesses T cell regulatory activity. Animals treated with MOTS-c had preserved insulin production and improved blood glucose levels compared with controls. They also had significantly delayed onset of diabetes or no diabetes at all. The discovery that patients with type 1 diabetes have unusually low levels of MOTS-c suggests novel treatments aimed at boosting the protein’s activity may be of clinical benefit.

Written by Ruth Williams

Image from work by Byung Soo Kong and colleagues

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea and Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Cell Reports, July 2021

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[neurosciencestuff]

Reading Minds with Ultrasound: A Less-Invasive Technique to Decode the Brain's Intentions

What is happening in your brain as you are scrolling through this page? In other words, which areas of your brain are active, which neurons are talking to which others, and what signals are they sending to your muscles?

Mapping neural activity to corresponding behaviors is a major goal for neuroscientists developing brain–machine interfaces (BMIs): devices that read and interpret brain activity and transmit instructions to a computer or machine. Though this may seem like science fiction, existing BMIs can, for example, connect a paralyzed person with a robotic arm; the device interprets the person's neural activity and intentions and moves the robotic arm correspondingly.

A major limitation for the development of BMIs is that the devices require invasive brain surgery to read out neural activity. But now, a collaboration at Caltech has developed a new type of minimally invasive BMI to read out brain activity corresponding to the planning of movement. Using functional ultrasound (fUS) technology, it can accurately map brain activity from precise regions deep within the brain at a resolution of 100 micrometers (the size of a single neuron is approximately 10 micrometers).

The new fUS technology is a major step in creating less invasive, yet still highly capable, BMIs.

"Invasive forms of brain–machine interfaces can already give movement back to those who have lost it due to neurological injury or disease," says Sumner Norman, postdoctoral fellow in the Andersen lab and co-first author on the new study. "Unfortunately, only a select few with the most severe paralysis are eligible and willing to have electrodes implanted into their brain. Functional ultrasound is an incredibly exciting new method to record detailed brain activity without damaging brain tissue. We pushed the limits of ultrasound neuroimaging and were thrilled that it could predict movement. What's most exciting is that fUS is a young technique with huge potential—this is just our first step in bringing high performance, less invasive BMI to more people."

The new study is a collaboration between the laboratories of Richard Andersen, James G. Boswell Professor of Neuroscience and Leadership Chair and director of the Tianqiao and Chrissy Chen Brain–Machine Interface Center in the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech; and of Mikhail Shapiro, professor of chemical engineering and Heritage Medical Research Institute Investigator. Shapiro is an affiliated faculty member with the Chen Institute.

A paper describing the work appeared in the journal Neuron.

In general, all tools for measuring brain activity have drawbacks. Implanted electrodes (electrophysiology) can very precisely measure activity on the level of single neurons, but, of course, require the implantation of those electrodes into the brain. Non-invasive techniques like functional magnetic resonance imaging (fMRI) can image the entire brain but require bulky and expensive machinery. Electroencephalography (EEGs) does not require surgery but can only measure activity at low spatial resolution.

Ultrasound works by emitting pulses of high frequency sound and measuring how those sound vibrations echo throughout a substance, such as various tissues of the human body. Sound travels at different speeds through these tissue types and reflects at the boundaries between them. This technique is commonly used to take images of a fetus in utero, and for other diagnostic imaging.

Ultrasound can also "hear" the internal motion of organs. For example, red blood cells, like a passing ambulance, will increase in pitch as they approach the source of the ultrasound waves, and decrease as they flow away. Measuring this phenomenon allowed the researchers to record tiny changes in the brain's blood flow down to 100 micrometers (on the scale of the width of a human hair).

"When a part of the brain becomes more active, there's an increase in blood flow to the area. A key question in this work was: If we have a technique like functional ultrasound that gives us high-resolution images of the brain's blood flow dynamics in space and over time, is there enough information from that imaging to decode something useful about behavior?" Shapiro says. "The answer is yes. This technique produced detailed images of the dynamics of neural signals in our target region that could not be seen with other non-invasive techniques like fMRI. We produced a level of detail approaching electrophysiology, but with a far less invasive procedure."

The collaboration began when Shapiro invited Mickael Tanter, a pioneer in functional ultrasound and director of Physics for Medicine Paris (ESPCI Paris Sciences et Lettres University, Inserm, CNRS), to give a seminar at Caltech in 2015. Vasileios Christopoulos, a former Andersen lab postdoctoral scholar (now an assistant professor at UC Riverside), attended the talk and proposed a collaboration. Shapiro, Andersen, and Tanter then received an NIH BRAIN Initiative grant to pursue the research. The work at Caltech was led by Norman, former Shapiro lab postdoctoral fellow David Maresca (now assistant professor at Delft University of Technology), and Christopoulos. Along with Norman, Maresca and Christopoulos are co-first authors on the new study.

The technology was developed with the aid of non-human primates, who were taught to do simple tasks that involved moving their eyes or arms in certain directions when presented with certain cues. As the primates completed the tasks, the fUS measured brain activity in the posterior parietal cortex (PPC), a region of the brain involved in planning movement. The Andersen lab has studied the PPC for decades and has previously created maps of brain activity in the region using electrophysiology. To validate the accuracy of fUS, the researchers compared brain imaging activity from fUS to previously obtained detailed electrophysiology data.

Next, through the support of the T&C Chen Brain–Machine Interface Center at Caltech, the team aimed to see if the activity-dependent changes in the fUS images could be used to decode the intentions of the non-human primate, even before it initiated a movement. The ultrasound imaging data and the corresponding tasks were then processed by a machine-learning algorithm, which learned what patterns of brain activity correlated with which tasks. Once the algorithm was trained, it was presented with ultrasound data collected in real time from the non-human primates.

The algorithm predicted, within a few seconds, what behavior the non-human primate was going to carry out (eye movement or reach), direction of the movement (left or right), and when they planned to make the movement.

"The first milestone was to show that ultrasound could capture brain signals related to the thought of planning a physical movement," says Maresca, who has expertise in ultrasound imaging. "Functional ultrasound imaging manages to record these signals with 10 times more sensitivity and better resolution than functional MRI. This finding is at the core of the success of brain–machine interfacing based on functional ultrasound."

"Current high-resolution brain–machine interfaces use electrode arrays that require brain surgery, which includes opening the dura, the strong fibrous membrane between the skull and the brain, and implanting the electrodes directly into the brain. But ultrasound signals can pass through the dura and brain non-invasively. Only a small, ultrasound-transparent window needs to be implanted in the skull; this surgery is significantly less invasive than that required for implanting electrodes," says Andersen.

Though this research was carried out in non-human primates, a collaboration is in the works with Dr. Charles Liu, a neurosurgeon at USC, to study the technology with human volunteers who, because of traumatic brain injuries, have had a piece of skull removed. Because ultrasound waves can pass unaffected through these "acoustic windows," it will be possible to study how well functional ultrasound can measure and decode brain activity in these individuals.

[neurosciencestuff]

Regular caffeine consumption affects brain structure

Coffee, cola or an energy drink: caffeine is the world’s most widely consumed psychoactive substance. Researchers from the University of Basel have now shown in a study that regular caffeine intake can change the gray matter of the brain. However, the effect appears to be temporary.

No question – caffeine helps most of us to feel more alert. However, it can disrupt our sleep if consumed in the evening. Sleep deprivation can in turn affect the gray matter of the brain, as previous studies have shown. So can regular caffeine consumption affect brain structure due to poor sleep? A research team led by Dr. Carolin Reichert and Professor Christian Cajochen of the University of Basel and UPK (the Psychiatric Hospital of the University of Basel) investigated this question in a study.

The result was surprising: the caffeine consumed as part of the study did not result in poor sleep. However, the researchers observed changes in the gray matter, as they report in the journal Cerebral Cortex. Gray matter refers to the parts of the central nervous system made up primarily of the cell bodies of nerve cells, while white matter mainly comprises the neural pathways, the long extensions of the nerve cells.

A group of 20 healthy young individuals, all of whom regularly drink coffee on a daily basis, took part in the study. They were given tablets to take over two 10-day periods, and were asked not to consume any other caffeine during this time. During one study period, they received tablets with caffeine; in the other, tablets with no active ingredient (placebo). At the end of each 10-day period, the researchers examined the volume of the subjects’ gray matter by means of brain scans. They also investigated the participants’ sleep quality in the sleep laboratory by recording the electrical activity of the brain (EEG).

Sleep unaffected, but not gray matter

Data comparison revealed that the participants’ depth of sleep was equal, regardless of whether they had taken the caffeine or the placebo capsules. But they saw a significant difference in the gray matter, depending on whether the subject had received caffeine or the placebo. After 10 days of placebo – i.e. “caffeine abstinence” – the volume of gray matter was greater than following the same period of time with caffeine capsules.

The difference was particularly striking in the right medial temporal lobe, including the hippocampus, a region of the brain that is essential to memory consolidation. “Our results do not necessarily mean that caffeine consumption has a negative impact on the brain,” emphasizes Reichert. “But daily caffeine consumption evidently affects our cognitive hardware, which in itself should give rise to further studies.” She adds that in the past, the health effects of caffeine have been investigated primarily in patients, but there is also a need for research on healthy subjects.

Although caffeine appears to reduce the volume of gray matter, after just 10 days of coffee abstinence it had significantly regenerated in the test subjects. “The changes in brain morphology seem to be temporary, but systematic comparisons between coffee drinkers and those who usually consume little or no caffeine have so far been lacking," says Reichert.

[neurosciencestuff]

Regular caffeine consumption affects brain structure

Coffee, cola or an energy drink: caffeine is the world’s most widely consumed psychoactive substance. Researchers from the University of Basel have now shown in a study that regular caffeine intake can change the gray matter of the brain. However, the effect appears to be temporary.

No question – caffeine helps most of us to feel more alert. However, it can disrupt our sleep if consumed in the evening. Sleep deprivation can in turn affect the gray matter of the brain, as previous studies have shown. So can regular caffeine consumption affect brain structure due to poor sleep? A research team led by Dr. Carolin Reichert and Professor Christian Cajochen of the University of Basel and UPK (the Psychiatric Hospital of the University of Basel) investigated this question in a study.

The result was surprising: the caffeine consumed as part of the study did not result in poor sleep. However, the researchers observed changes in the gray matter, as they report in the journal Cerebral Cortex. Gray matter refers to the parts of the central nervous system made up primarily of the cell bodies of nerve cells, while white matter mainly comprises the neural pathways, the long extensions of the nerve cells.

A group of 20 healthy young individuals, all of whom regularly drink coffee on a daily basis, took part in the study. They were given tablets to take over two 10-day periods, and were asked not to consume any other caffeine during this time. During one study period, they received tablets with caffeine; in the other, tablets with no active ingredient (placebo). At the end of each 10-day period, the researchers examined the volume of the subjects’ gray matter by means of brain scans. They also investigated the participants’ sleep quality in the sleep laboratory by recording the electrical activity of the brain (EEG).

Sleep unaffected, but not gray matter

Data comparison revealed that the participants’ depth of sleep was equal, regardless of whether they had taken the caffeine or the placebo capsules. But they saw a significant difference in the gray matter, depending on whether the subject had received caffeine or the placebo. After 10 days of placebo – i.e. “caffeine abstinence” – the volume of gray matter was greater than following the same period of time with caffeine capsules.

The difference was particularly striking in the right medial temporal lobe, including the hippocampus, a region of the brain that is essential to memory consolidation. “Our results do not necessarily mean that caffeine consumption has a negative impact on the brain,” emphasizes Reichert. “But daily caffeine consumption evidently affects our cognitive hardware, which in itself should give rise to further studies.” She adds that in the past, the health effects of caffeine have been investigated primarily in patients, but there is also a need for research on healthy subjects.

Although caffeine appears to reduce the volume of gray matter, after just 10 days of coffee abstinence it had significantly regenerated in the test subjects. “The changes in brain morphology seem to be temporary, but systematic comparisons between coffee drinkers and those who usually consume little or no caffeine have so far been lacking," says Reichert.

[mednerds]

COVID-19 vaccines

The basic principle of vaccination is to prime the immune system so it is better prepared to meet a pathogen. Historically, the earliest way to accomplish this was to get a mild infection that conferred immunity to a stronger disease; for example, exposure to cowpox to prevent getting the much more deadly smallpox. Modern approaches use weakened or inactivated viruses, or even fragments of a virus, but the principle remains the same: safely expose the immune system to a pathogen so immune cells learn to recognize it and can react quickly and effectively the next time it appears.

In the case of COVID-19, some of the vaccines use a new technique based around messenger RNA (mRNA). In this approach, patients are never exposed to the virus, even in a weakened form. Instead, the vaccine carries mRNA from a key virus gene that makes the spike protein. Once inside cells, the mRNA serves as a template to make the spike protein, and our immune system then learns about it and is ready to fight off the virus. The mRNA template is then quickly degraded by our normal cellular processes.

When enough people are vaccinated, a disease can no longer spread through the population. That’s how vaccination campaigns have helped bring many diseases under control. COVID-19 vaccines have been developed on an accelerated timeline because of the exceptional circumstances, but they nevertheless went through the entire regulatory review and approval process. Though there will be immense logistical challenges in ensuring that everyone has timely access to a vaccine, we are one step closer to a post COVID-19 world.

Conceptualized by: Sedeer el-Showk Design: Youssef Khalil. Nature.

[themedicalstate]

Inside the B.1.1.7 Coronavirus Variant

At the heart of each coronavirus is its genome, a twisted strand of nearly 30,000 “letters” of RNA. These genetic instructions force infected human cells to assemble up to 29 kinds of proteins that help the coronavirus multiply and spread.

As viruses replicate, small copying errors known as mutations naturally arise in their genomes. A lineage of coronaviruses will typically accumulate one or two random mutations each month.

Some mutations have no effect on the coronavirus proteins made by the infected cell. Other mutations might alter a protein’s shape by changing or deleting one of its amino acids, the building blocks that link together to form the protein.

Through the process of natural selection, neutral or slightly beneficial mutations may be passed down from generation to generation, while harmful mutations are more likely to die out.

Mutations In the B.1.1.7 Lineage

A coronavirus variant first reported in Britain has 17 recent mutations that change or delete amino acids in viral proteins.

The variant was named Variant of Concern 202012/01 by Public Health England, and is part of the B.1.1.7 lineage of coronaviruses.

Notable mutations in the B.1.1.7 lineage are listed below. Six other mutations, not shown in the diagram above, do not change an amino acid.

Eight Spike Mutations

Researchers are most concerned about the eight B.1.1.7 mutations that change the shape of the coronavirus spike, which the virus uses to attach to cells and slip inside.

Each spike is a group of three intertwined proteins:

Building one of these spike proteins typically takes 1,273 amino acids, which can be written as letters:

Spike proteins in the B.1.1.7 lineage have two deletions and six substitutions in this sequence of amino acids.

Written as letters, a B.1.1.7 spike protein looks like this:

These mutations alter the shape of the spike protein by changing how the amino acids fold together into a complex shape.

The Spike N501Y Mutation

Scientists suspect that one mutation, called N501Y, is very important in making B.1.1.7 coronaviruses more contagious. The mutation’s name refers to the nature of its change: the 501st amino acid in the spike protein switched from N (asparagine) to Y (tyrosine).

The N501Y mutation changes an amino acid near the top of each spike protein, where it makes contact with a special receptor on human cells.

Because spike proteins form sets of three, the mutation appears in three places on the spike tip:

In a typical coronavirus, the tip of the spike protein is like an ill-fitting puzzle piece. It can latch onto human cells, but the fit is so loose that the virus often falls away and fails to infect the cell.

The N501Y mutation seems to refine the shape of the puzzle piece, allowing a tighter fit and increasing the chance of a successful infection.

Researchers think the N501Y mutation has evolved independently in many different coronaviruses lineages. In addition to the B.1.1.7 lineage, it has been identified in variants from Australia, Brazil, Denmark, Japan, the Netherlands, South Africa, Wales, Illinois, Louisiana, Ohio and Texas.

In addition to N501Y, the B.1.1.7 has 16 other mutations that might benefit the virus in other ways. It’s also possible that they might be neutral mutations, which have no effect one way or the other. They may simply be passed down from generation to generation like old baggage. Scientists are running experiments to find out which is the case for each mutation.

One mysterious mutation in the B.1.1.7 lineage deletes the 69th and 70th amino acids in the spike protein. Experiments have shown that this deletion enables the coronavirus to infect cells more successfully. It’s possible that it changes the shape of the spike protein in a way that makes it harder for antibodies to attach.

Researchers call this a recurrent deletion region because the same part of the genome has been repeatedly deleted in different lineages of coronaviruses. The H69–V70 deletion also occurred in a variant that infected millions of mink in Denmark and other countries. Scientists are beginning to identify a number of these regions, which may play an important role in the virus’s future evolution.

In another recurrent deletion region, a number of coronavirus lineages are missing either the 144th or 145th amino acid in the spike protein. The name of the mutation comes from the two tyrosines (Y) that are normally in those positions in the protein.

Like the H69–V70 deletion, Y144/145 occurs on the edge of the spike tip. It may also make it harder for antibodies to stick to the coronavirus.

This mutation changes an amino acid from P to H on the stem of the coronavirus spike:

When spike proteins are assembled on the surface of a coronavirus, they’re not yet ready to attach to a cell. A human enzyme must first cut apart a section of the spike stem. The P681H mutation may make it easier for the enzyme to reach the site where it needs to make its cut.

Like N501Y, the P681H mutation has arisen in other coronavirus lineages besides B.1.1.7. But it’s rare for one lineage to carry both mutations.

ORF8 is a small protein whose function remains mysterious. In one experiment, scientists deleted the protein and found that the coronavirus could still spread. That suggests that ORF8 is not essential to replication, but it might still give some competitive edge over mutants that have lost the protein.

ORF8 is typically only 121 amino acids long:

But a B.1.1.7 mutation changes the 27th amino acid from Q to a genetic Stop sign:

Researchers assume that this ORF8 stump cannot function. But if losing the protein leaves B.1.1.7 at a disadvantage, it’s possible that the advantages of another mutation like N501Y might make up for the loss.

Detection and Spread

B.1.1.7 first came to light in the United Kingdom in late November. Researchers looked back at earlier samples and found that the first evidence dates back to Sept. 20, in a sample taken from a patient near London.

The B.1.1.7 lineage has now been detected in over 50 countries, including the United States. Britain has responded to the surge of B.1.1.7 with stringent lockdowns, and other countries have tried to prevent its spread with travel restrictions.

B.1.1.7 is estimated to be roughly 50 percent more transmissible than other variants. Federal health officials warn that it may become the dominant variant in the United States by March. It is no more deadly than other forms of the coronavirus. But because it can cause so many more infections, it may lead to many more deaths.

B.1.1.7 has been detected in at least 14 states, but the United States has no national surveillance program for determining the full extent of its spread.

How Did the Variant Evolve?

A number of researchers suspect that B.1.1.7 gained many of its mutations within a single person. People with weakened immune systems can remain infected with replicating coronaviruses for several months, allowing the virus to accumulate many extra mutations.

When these patients are treated with convalescent plasma, which contains coronavirus antibodies, natural selection may favor viruses with mutations that let them escape the attack. Once the B.1.1.7 lineage evolved its battery of mutations, it may have been able to spread faster from person to person.

Other Mutations in Circulation

One of the first mutations that raised concerns among scientists is known as D614G. It emerged in China early in the pandemic and may have helped the virus spread more easily. In many countries, the D614G lineage came to dominate the population of coronaviruses. B.1.1.7 descends from the D614G lineage.

A more recent variant detected in South Africa quickly spread to several other countries. It is known as 501Y.V2 and is part of the B.1.351 lineage. This variant has eight mutations that change amino acids in the spike protein. Among these mutations is N501Y, which helps the spike latch on more tightly to human cells.

None of these variants are expected to help the coronavirus evade the many coronavirus vaccines in clinical trials around the world. Antibodies generated by the Pfizer-BioNTech vaccine were able to lock on to coronavirus spikes that have the N501Y spike mutation, preventing the virus from infecting cells in the lab.

Experts stress that it would likely take many years, and many more mutations, for the virus to evolve enough to avoid current vaccines.

Sources: Andrew Rambaut et al., Virological; Andrew Ward, Scripps Research; Trevor Bedford, nextstrain.org; Paul Duprex, University of Pittsburgh School of Medicine; Houriiyah Tegally et al., medRxiv; Nature; Centers for Disease Control and Prevention; Global Report Investigating Novel Coronavirus Haplotypes. Spike models from Ward Lab, Scripps Research. Spike-receptor model by Cong Lab, Chinese Academy of Sciences. ORF8 model by the Yang Zhang Research Group, University of Michigan. Cahill-Keyes map projection by Gene Keyes. By Jonathan Corum and Carl Zimmer (The New York Times).

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New study suggests exercise is good for the aging brain

Exercise seems to endow a wealth of benefits, from the release of happiness-inducing hormones to higher physical fitness. New research shows it may provide a boost to the mind too.

University of Iowa researchers have found that a single bout of exercise improves cognitive functions and working memory in some older people. In experiments that included physical activity, brain scans, and working memory tests, the researchers also found that participants experienced the same cognitive benefits and improved memory from a single exercise session as they did from longer, regular exercise.

“One implication of this study is you could think of the benefits day by day,” says Michelle Voss, assistant professor in the Department of Psychological and Brain Sciences and the study’s corresponding author. “In terms of behavioral change and cognitive benefits from physical activity, you can say, ‘I’m just going to be active today. I’ll get a benefit.’ So, you don’t need to think of it like you’re going to train for a marathon to get some sort of optimal peak of performance. You just could work at it day by day to gain those benefits.”

Previous research has shown exercise can confer a mental boost. But the benefits vary: One person may improve cognitively and have improved memory, while another person may show little to no gain.

Limited research has been done on how a single bout of physical activity may affect cognition and working memory specifically in older populations, despite evidence that some brain functions slip as people age.

Voss wanted to tease out how a single session of exercise may affect older individuals. Her team enrolled 34 adults between 60 and 80 years of age who were healthy but not regularly active. Each participant rode a stationary bike on two separate occasions—with light and then more strenuous resistance when pedaling—for 20 minutes. Before and after each exercise session, each participant underwent a brain scan and completed a memory test.

In the brain scan, the researchers examined bursts of activity in regions known to be involved in the collection and sharing of memories. In the working memory tests, each participant used a computer screen to look at a set of eight young adult faces that rotated every three seconds—flashcard style—and had to decide when a face seen two “cards” previously matched the one they were currently viewing.

After a single exercise session, the researchers found in some individuals increased connectivity between the medial temporal (which surrounds the brain’s memory center, the hippocampus) and the parietal cortex and prefrontal cortex, two regions involved in cognition and memory. Those same individuals also performed better on the memory tests. Other individuals showed little to no gain.

The boost in cognition and memory from a single exercise session lasted only a short while for those who showed gains, the researchers found.

“The benefits can be there a lot more quickly than people think,” Voss says. “The hope is that a lot of people will then keep it up because those benefits to the brain are temporary. Understanding exactly how long the benefits last after a single session, and why some benefit more than others, are exciting directions for future research.”

The participants also engaged in regular exercise, pedaling on a stationary bike for 50 minutes three times a week for three months. One group engaged in moderate-intensity pedaling, while another group had a mostly lighter workout in which the bike pedals moved for them.

Most individuals in the moderate and lighter-intensity groups showed mental benefits, judging by the brain scans and working memory tests given at the beginning and at the end of the three-month exercise period. But the brain gains were no greater than the improvements from when they had exercised a single time.

“The result that a single session of aerobic exercise mimics the effects of 12 weeks of training on performance has important implications both practically and theoretically,” the authors write.

The researchers note their study had a small participant pool, with a homogenous population that excluded anyone with chronic health conditions or who were taking beta-blockers.

To address those limitations, Voss has expanded her participant pool in a current, five-year study to confirm the initial findings and learn more about how exercise alters older people’s brains. The participants are healthy older individuals who are not physically active, similar to the participants’ profile in the study’s results reported here.

[bpod-bpod]

Articulating Words

Expressing ourselves through language is a unique trait that distinguishes us from other species. But what exactly happens in our brain during speech? A team of scientists set out to map brain activity before, during, and after we speak, focusing on the insula, a region in the middle of the brain whose role in language has puzzled neuroscientists for several years. By mapping brain activation patterns of individuals with electrodes implanted in their head as they performed speech and listening tasks, the team could identify which regions were most active before, during, and after speech. Before participants read out individual words (first half of video), most activity (in red/yellow clusters) was at the front of the brain. The insula only lit up after participants articulated words and sounds. Mapping the insula’s role during speech could help scientists to better understand the types of speech disorders that may develop after brain injury.

Written by Gaëlle Coullon

Video from work by Oscar Woolnough and colleagues

Vivian L. Smith Department of Neurosurgery, McGovern Medical School at UT Health Houston, Houston, TX, USA

Video originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in eLife, December 2019

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[neurosciencestuff]

Are you with me? New model explains origins of empathy

Researchers at the Max Planck Institute and the Santa Fe Institute have developed a new model to explain the evolutionary origins of empathy and other related phenomena, such as emotional contagion and contagious yawning. The model suggests that the origin of a broad range of empathetic responses lies in cognitive simulation. It shifts the theoretical focus from a top-down approach that begins with cooperation to one that begins with a single cognitive mechanism.

According to Fabrizio Mafessoni, who is a post-doctoral researcher at the Max Planck Institute for Evolutionary Anthropology, standard theoretical models of the origins of empathy tend to focus on scenarios in which coordination or cooperation are favored.

Mafessoni, and his co-author Michael Lachmann, a theoretical biologist and Professor at the Santa Fe Institute, explored the possibility that the cognitive processes underlying a broad range of empathetic responses — including emotional contagion, contagious yawning, and pathologies like echopraxia (compulsive repetition of others’ movements) and echolalia (compulsive repetition of others’ speech) — could evolve in the absence of kin selection or any other mechanism directly favoring cooperation or coordination.

Mafessoni and Lachmann posited that animals, including humans, can engage in the act of simulating the minds of others. We cannot read other minds — they are like black boxes to us. But, as Lachmann explains, all agents share almost identical “black boxes” with members of their species, and “they are constantly running simulations of what other minds might be doing.” This ongoing as-actor simulation is not necessarily geared toward cooperation: it’s just something humans and animals do spontaneously.

An example of this process is represented by mirror neurons: it has been known for some time that the same neurons engaged in planning a hand movement are also used when observing the hand movement of others. Mafessoni and Lachmann wondered what the consequences would be if they were to extend that process of understanding to any social interaction.

When they modeled outcomes rooted in cognitive simulation, they found that actors engaged in as-actor simulation produce a variety of systems typically explained in terms of cooperation or kin-selection. They also found that an observer can occasionally coordinate with an actor even when this outcome is not advantageous. Their model suggests that empathetic systems do not evolve solely because agents are disposed to cooperation and kin-selection. They also evolve because animals simulate others to envision their actions. According to Mafessoni, “the very origin of empathy may lie in the need to understand other individuals.”

For Lachmann, their findings “completely change how we think about humans and animals.” Their model is grounded in a single, cognitive mechanism that unifies a broad set of phenomena under one explanation. It therefore has theoretical import for a wide range of fields, including cognitive psychology, anthropology, neuroscience, complex systems, and evolutionary biology. Its power stems from both its unifying clarity and its theoretical interest in the limits of cooperation as an explanatory frame.