Such rhythmic waves linked to state of consciousness

Date:
March 29, 2018

Source:
Washington University School of Medicine

Summary:
Very slow brain waves, long considered an artifact of brain scanning techniques, may be more important than anyone had realized. Researchers have found that very slow waves are directly linked to state of consciousness and may be involved in coordinating activity across distant brain regions.

 

Brain concept (stock illustration).
Credit: © phonlamaiphoto / Fotolia

 

 

If you keep a close eye on an MRI scan of the brain, you’ll see a wave pass through the entire brain like a heartbeat once every few seconds. This ultra-slow rhythm was recognized decades ago, but no one quite knew what to make of it. MRI data are inherently noisy, so most researchers simply ignored the ultra-slow waves.

But by studying electrical activity in mouse brains, researchers at Washington University School of Medicine in St. Louis have found that the ultra-slow waves are anything but noise. They are more like waves in the sea, with everything the brain does taking place in boats upon that sea. Research to date has been focused on the goings-on inside the boats, without much thought for the sea itself. But the new information suggests that the waves play a central role in how the complex brain coordinates itself and that the waves are directly linked to consciousness.

“Your brain has 100 billion neurons or so, and they have to be coordinated,” said senior author Marcus Raichle, MD, the Alan A. and Edith L. Wolff Distinguished Professor of Medicine and a professor of radiology at Mallinckrodt Institute of Radiology at the School of Medicine. “These slowly varying signals in the brain are a way to get a very large-scale coordination of the activities in all the diverse areas of the brain. When the wave goes up, areas become more excitable; when it goes down, they become less so.”

The study is published March 29 in the journal Neuron.

In the early 2000s, Raichle and others discovered patterns of brain activity in people as they lay quietly in MRI machines, letting their minds wander. These so-called resting-state networks challenged the assumption that the brain quiets itself when it’s not actively engaged in a task. Now we know that even when you feel like you’re doing nothing, your brain is still humming along, burning almost as much energy daydreaming as solving a tough math problem.

Using resting-state networks, other researchers started searching for — and finding — brain areas that behaved differently in healthy people than in people with brain diseases such as schizophrenia and Alzheimer’s. But even as resting-state MRI data provided new insights into neuropsychiatric disorders, they also consistently showed waves of activity spreading with a slow regularity throughout the brain, independently of the disease under study. Similar waves were seen on brain scans of monkeys and rodents.

Some researchers thought that these ultra-slow waves were no more than an artifact of the MRI technique itself. MRI gauges brain activity indirectly by measuring the flow of oxygen-rich blood over a period of seconds, a very long timescale for an organ that sends messages at one-tenth to one-hundredth of a second. Rather than a genuinely slow process, the reasoning went, the waves could be the sum of many rapid electrical signals over a relatively long time.

First author Anish Mitra, PhD, and Andrew Kraft, PhD — both MD/PhD students at Washington University — and colleagues decided to approach the mystery of the ultra-slow waves using two techniques that directly measure electrical activity in mice brains. In one, they measured such activity on the cellular level. In the other, they measured electrical activity layer by layer along the outer surface of the brain.

They found that the waves were no artifact: Ultra-slow waves were seen regardless of the technique, and they were not the sum of all the faster electrical activity in the brain.

Instead, the researchers found that the ultra-slow waves spontaneously started in a deep layer of mice’s brains and spread in a predictable trajectory. As the waves passed through each area of the brain, they enhanced the electrical activity there. Neurons fired more enthusiastically when a wave was in the vicinity.

Moreover, the ultra-slow waves persisted when the mice were put under general anesthesia, but with the direction of the waves reversed.

“There is a very slow process that moves through the brain to create temporary windows of opportunity for long-distance signaling,” Mitra said. “The way these ultra-slow waves move through the cortex is correlated with enormous changes in behavior, such as the difference between conscious and unconscious states.”

The fact that the waves’ trajectory changed so dramatically with state of consciousness suggests that ultra-slow waves could be fundamental to how the brain functions. If brain areas are thought of as boats bobbing about on a slow-wave sea, the choppiness and direction of the sea surely influences how easily a message can be passed from one boat to another, and how hard it is for two boats to coordinate their activity.

The researchers now are studying whether abnormalities in the trajectory of such ultra-slow waves could explain some of the differences seen on MRI scans between healthy people and people with neuropsychiatric conditions such as dementia and depression.

“If you look at the brain of someone with schizophrenia, you don’t see a big lesion, but something is not right in how the whole beautiful machinery of the brain is organized,” said Raichle, who is also a professor of biomedical engineering, of neurology, of neuroscience and of psychological and brain sciences. “What we’ve found here could help us figure out what is going wrong. These very slow waves are unique, often overlooked and utterly central to how the brain is organized. That’s the bottom line.”

Story Source:

Materials provided by Washington University School of Medicine. Original written by Tamara Bhandari. Note: Content may be edited for style and length.


Journal Reference:

  1. Anish Mitra, Andrew Kraft, Patrick Wright, Benjamin Acland, Abraham Z. Snyder, Zachary Rosenthal, Leah Czerniewski, Adam Bauer, Lawrence Snyder, Joseph Culver, Jin-Moo Lee, Marcus E. Raichle. Spontaneous Infra-slow Brain Activity Has Unique Spatiotemporal Dynamics and Laminar StructureNeuron, 2018; DOI: 10.1016/j.neuron.2018.03.015

 

Source: Washington University School of Medicine. “Slow, steady waves keep brain humming: Such rhythmic waves linked to state of consciousness.” ScienceDaily. ScienceDaily, 29 March 2018. <www.sciencedaily.com/releases/2018/03/180329141012.htm>.

Date:
March 28, 2018

Source:
NASA/Goddard Space Flight Center

Summary:
Galaxies and dark matter go together like peanut butter and jelly. You typically don’t find one without the other.

 

This large, fuzzy-looking galaxy is so diffuse that astronomers call it a ‘see-through’ galaxy because they can clearly see distant galaxies behind it. The ghostly object, catalogued as NGC 1052-DF2, doesn’t have a noticeable central region, or even spiral arms and a disk, typical features of a spiral galaxy. But it doesn’t look like an elliptical galaxy, either. Even its globular clusters are oddballs: they are twice as large as typical stellar groupings seen in other galaxies. All of these oddities pale in comparison to the weirdest aspect of this galaxy: NGC 1052-DF2 is missing most, if not all, of its dark matter.
Credit: NASA, ESA, and P. van Dokkum (Yale University)

 

 

Galaxies and dark matter go together like peanut butter and jelly. You typically don’t find one without the other.

Therefore, researchers were surprised when they uncovered a galaxy that is missing most, if not all, of its dark matter. An invisible substance, dark matter is the underlying scaffolding upon which galaxies are built. It’s the glue that holds the visible matter in galaxies — stars and gas — together.

“We thought that every galaxy had dark matter and that dark matter is how a galaxy begins,” said Pieter van Dokkum of Yale University in New Haven, Connecticut, lead researcher of the Hubble observations. “This invisible, mysterious substance is the most dominant aspect of any galaxy. So finding a galaxy without it is unexpected. It challenges the standard ideas of how we think galaxies work, and it shows that dark matter is real: it has its own separate existence apart from other components of galaxies. This result also suggests that there may be more than one way to form a galaxy.”

The unique galaxy, called NGC 1052-DF2, contains at most 1/400th the amount of dark matter that astronomers had expected. The galaxy is as large as our Milky Way, but it had escaped attention because it contains only 1/200th the number of stars. Given the object’s large size and faint appearance, astronomers classify NGC 1052-DF2 as an ultra-diffuse galaxy. A 2015 survey of the Coma galaxy cluster showed these large, faint objects to be surprisingly common.

But none of the ultra-diffuse galaxies discovered so far have been found to be lacking in dark matter. So even among this unusual class of galaxy, NGC 1052-DF2 is an oddball.

Van Dokkum and his team spotted the galaxy with the Dragonfly Telephoto Array, a custom-built telescope in New Mexico they designed to find these ghostly galaxies. They then used the W.M. Keck Observatory in Hawaii to measure the motions of 10 giant groupings of stars called globular clusters in the galaxy. Keck revealed that the globular clusters were moving at relatively low speeds, less than 23,000 miles per hour. Stars and clusters in the outskirts of galaxies containing dark matter move at least three times faster. From those measurements, the team calculated the galaxy’s mass. “If there is any dark matter at all, it’s very little,” van Dokkum explained. “The stars in the galaxy can account for all the mass, and there doesn’t seem to be any room for dark matter.”

The researchers next used NASA’s Hubble Space Telescope and the Gemini Observatory in Hawaii to uncover more details about the unique galaxy. Gemini revealed that the galaxy does not show signs of an interaction with another galaxy. Hubble helped them better identify the globular clusters and measure an accurate distance to the galaxy.

The Hubble images also revealed the galaxy’s unusual appearance. “I spent an hour just staring at the Hubble image,” van Dokkum recalled. “It’s so rare, particularly these days after so many years of Hubble, that you get an image of something and you say, ‘I’ve never seen that before.’ This thing is astonishing: a gigantic blob that you can look through. It’s so sparse that you see all of the galaxies behind it. It is literally a see-through galaxy.”

The ghostly galaxy doesn’t have a noticeable central region, or even spiral arms and a disk, typical features of a spiral galaxy. But it doesn’t look like an elliptical galaxy, either. The galaxy also shows no evidence that it houses a central black hole. Based on the colors of its globular clusters, the galaxy is about 10 billion years old. Even the globular clusters are oddballs: they are twice as large as typical stellar groupings seen in other galaxies.

“It’s like you take a galaxy and you only have the stellar halo and globular clusters, and it somehow forgot to make everything else,” van Dokkum said. “There is no theory that predicted these types of galaxies. The galaxy is a complete mystery, as everything about it is strange. How you actually go about forming one of these things is completely unknown.”

But the researchers do have some ideas. NGC 1052-DF2 resides about 65 million light-years away in a collection of galaxies that is dominated by the giant elliptical galaxy NGC 1052. Galaxy formation is turbulent and violent, and van Dokkum suggests that the growth of the fledgling massive galaxy billions of years ago perhaps played a role in NGC 1052-DF2’s dark-matter deficiency.

Another idea is that gas moving toward the giant elliptical NGC 1052 may have fragmented and formed NGC 1052-DF2. The formation of NGC 1052-DF2 may have been helped by powerful winds emanating from the young black hole that was growing in the center of NGC 1052. These possibilities are speculative, however, and don’t explain all of the characteristics of the observed galaxy, the researchers said.

The team is already hunting for more dark-matter deficient galaxies. They are analyzing Hubble images of 23 other diffuse galaxies. Three of them appear similar to NGC 1052-DF2.

“Every galaxy we knew about before has dark matter, and they all fall in familiar categories like spiral or elliptical galaxies,” van Dokkum said. “But what would you get if there were no dark matter at all? Maybe this is what you would get.”

Story Source:

Materials provided by NASA/Goddard Space Flight CenterNote: Content may be edited for style and length.


Journal Reference:

  1. Pieter van Dokkum, Shany Danieli, Yotam Cohen, Allison Merritt, Aaron J. Romanowsky, Roberto Abraham, Jean Brodie, Charlie Conroy, Deborah Lokhorst, Lamiya Mowla, Ewan O’Sullivan & Jielai Zhang. A galaxy lacking dark matterNature, 2018 DOI: 10.1038/nature25676

 

Source: NASA/Goddard Space Flight Center. “Dark matter goes missing in oddball galaxy.” ScienceDaily. ScienceDaily, 28 March 2018. <www.sciencedaily.com/releases/2018/03/180328130724.htm>.

Date:
March 27, 2018

Source:
College of Engineering, Carnegie Mellon University

Summary:
Researchers have developed a low-cost 3-D bioprinter by modifying a standard desktop 3-D printer, and they have released the breakthrough designs as open source so that anyone can build their own system.

 

PrintrBot Simple Metal modified with the LVE for FRESH printing.
Credit: Adam Feinberg/HardwareX

 

 

Researchers at Carnegie Mellon University have developed a low-cost 3-D bioprinter by modifying a standard desktop 3-D printer, and they have released the breakthrough designs as open source so that anyone can build their own system. The researchers — Materials Science and Engineering (MSE) and Biomedical Engineering (BME) Associate Professor Adam Feinberg, BME postdoctoral fellow TJ Hinton, and Kira Pusch, a recent graduate of the MSE undergraduate program — recently published a paper in the journal HardwareX that contains complete instructions for printing and installing the syringe-based, large volume extruder (LVE) to modify any typical, commercial plastic printer.

“What we’ve created,” says Pusch, “is a large volume syringe pump extruder that works with almost any open source fused deposition modeling (FDM) printer. This means that it’s an inexpensive and relatively easy adaptation for people who use 3-D printers.”

As the researchers explain in their paper, “Large volume syringe pump extruder for desktop 3D printers,” most commercial 3-D bioprinters currently on the market range in cost from $10,000 to more than $200,000 and are typically proprietary machines, closed source, and difficult to modify.

“Essentially, we’ve developed a bioprinter that you can build for under $500, that I would argue is at least on par with many that cost far more money,” says Feinberg, who is also a member of the Bioengineered Organs Initiative at Carnegie Mellon. “Most 3-D bioprinters start between $10K and $20K. This is significantly cheaper, and we provide very detailed instructional videos. It’s really about democratizing technology and trying to get it into more people’s hands.”

And not only does the LVE cut down on cost, it also allows users to print artificial human tissue on a larger scale and at higher resolution, opening doors for researchers, makers, and professionals to experiment with 3-D printing biomaterials and fluids.

“Usually there’s a trade-off,” explains Feinberg, “because when the systems dispense smaller amounts of material, we have more control and can print small items with high resolution, but as systems get bigger, various challenges arise. The LVE 3-D bioprinter allows us to print much larger tissue scaffolds, at the scale of an entire human heart, with high quality.”

“Bioprinting has historically been limited in volume,” adds Pusch, “so essentially the goal is to just scale up the process without sacrificing detail and quality of the print.”

Pusch, the first author on the paper, was a research assistant in Feinberg’s lab for three years during her undergraduate career. During that time, she received an International Summer Undergraduate Research Fellowship (iSURF) to work in the Netherlands, and also interned with General Electric’s Center for Additive Technology Advancement. Following her graduation from Carnegie Mellon in December of 2017, she began a spring internship at Formlabs in Boston and has since accepted a second internship position for the summer at Blue Origin in Seattle. Pusch has also co-authored a second paper in ACS Biomaterials Science & Engineering with Hinton, “3D Printing PDMS Elastomer in a Hydrophilic Support Bath via Freeform Reversible Embedding.” As a research assistant in Feinberg’s lab, Pusch was able to experience real-world application of her research early on in her academic career. When asked about her experience in Feinberg’s lab, Pusch emphasizes how grateful she is to have had the opportunity to work with such supportive and brilliant mentors.

In their paper, the researchers demonstrated the system using alginate, a common biomaterial for 3-D printing, and using the lab’s signature Freeform Reversible Embedding of Suspended Hydrogels (FRESH) technique.

Feinberg’s lab aims to produce open source biomedical research that other researchers can expand upon. By making their research widely accessible, Feinberg’s lab hopes to seed innovation widely, to encourage the rapid development of biomedical technologies to save lives.

“We envision this as being the first of many technologies that we push into the open source environment to drive the field forward,” says Feinberg. “It’s something we really believe in.”

Story Source:

Materials provided by College of Engineering, Carnegie Mellon UniversityNote: Content may be edited for style and length.


Journal Reference:

  1. Kira Pusch, Thomas J. Hinton, Adam W. Feinberg. Large volume syringe pump extruder for desktop 3D printersHardwareX, 2018; 3: 49 DOI: 10.1016/j.ohx.2018.02.001

 

Source: College of Engineering, Carnegie Mellon University. “3-DIY: Printing your own bioprinter.” ScienceDaily. ScienceDaily, 27 March 2018. <www.sciencedaily.com/releases/2018/03/180327132009.htm>.

Date:
March 26, 2018

Source:
University of Alaska Fairbanks

Summary:
Controlling greenhouse gas emissions in the coming decades could substantially reduce the consequences of carbon releases from thawing permafrost during the next 300 years, according to a new article.

 

Controlling greenhouse gas emissions in the coming decades could substantially reduce the consequences of carbon releases from thawing permafrost during the next 300 years, according to a new paper published this week in the Proceedings of National Academy of Sciences.

 

Conversely, climate policy that results in little or no effort to control greenhouse gases like carbon dioxide would likely result in a substantial release of carbon from the permafrost region by 2300, the study found.

A. David McGuire, U.S. Geological Survey senior scientist and climate system modeling expert with the University of Alaska Fairbanks Institute of Arctic Biology, is lead author of the paper. Several other UAF researchers, along with scientists from about two dozen other research institutions worldwide, contributed to the study.

Scientists estimate that the soils of the Earth’s circumpolar North contain about twice the amount of carbon as is in the atmosphere. Much of that carbon is frozen organic matter locked within permafrost. As global temperatures rise and permafrost thaws, the previously frozen organic material begins to decay and releases greenhouse gases like methane and carbon dioxide. The release of that carbon can, in turn, cause additional warming and the release of more carbon, something scientists call a positive feedback loop.

Even without immediate controls on greenhouse gases now, the bulk of the permafrost carbon release would not occur until after the year 2100. Study authors note that this could cause society to grow complacent and accept less aggressive efforts to control greenhouse gases. Waiting too long to institute controls could mean the controls come too late to prevent substantive loss of carbon from permafrost soils.

“Society can do something about this, at least that’s what the state-of-the-art models are saying,” McGuire said.

The degree to which climate change could influence carbon dynamics in the northern permafrost region has important implications for policy decisions. However, most climate system models have not done a good job of showing the relationship between permafrost and soil carbon dynamics. Because of that, they haven’t allowed an accurate assessment of the effects of climate change on carbon in the region.

In the new study, McGuire and his colleagues used simulations to study changes in permafrost and carbon storage in the northern permafrost region from 2010 to 2299 using two climate change scenarios: One with low carbon dioxide emissions and one with high carbon dioxide emissions. Permafrost expert Dmitry Nicolsky of the UAF Geophysical Institute provided simulation data on changes in the extent of permafrost in the northern hemisphere and the predicted thaw depth under the two scenarios.

The low emission scenario would require carbon emissions by global human society to decrease by 75 percent during this century. In that scenario, the study showed the loss 3 million to 5 million square kilometers of permafrost and changes in soil carbon ranging from a 66-petagram loss to a 70-petagram gain. One petagram equals one trillion kilograms or 2.2 trillion pounds.

In the high emission scenario, or essentially no change in current trends of fossil fuel use, permafrost losses were between 6 million and 16 million square kilometers, while soil carbon losses varied from 74 to 652 petagrams and occur mostly after 2100. This represents a loss of 20 to 63 percent of the carbon now stored in northern permafrost.

The findings suggest that effective new greenhouse gas controls could help lessen the effects of climate change on the release of carbon from soils of the northern permafrost region and therefore decrease the potential for a positive feedback of permafrost carbon release on climate warming.

“If such controls aren’t adopted, it will lead to major changes for ecosystems and infrastructure,” Nicolsky said.

Story Source:

Materials provided by University of Alaska FairbanksNote: Content may be edited for style and length.


Journal Reference:

  1. A. David McGuire, David M. Lawrence, Charles Koven, Joy S. Clein, Eleanor Burke, Guangsheng Chen, Elchin Jafarov, Andrew H. MacDougall, Sergey Marchenko, Dmitry Nicolsky, Shushi Peng, Annette Rinke, Philippe Ciais, Isabelle Gouttevin, Daniel J. Hayes, Duoying Ji, Gerhard Krinner, John C. Moore, Vladimir Romanovsky, Christina Schädel, Kevin Schaefer, Edward A. G. Schuur, Qianlai Zhuang. Dependence of the evolution of carbon dynamics in the northern permafrost region on the trajectory of climate changeProceedings of the National Academy of Sciences, 2018; 201719903 DOI: 10.1073/pnas.1719903115

 

Source: University of Alaska Fairbanks. “Climate policy, carbon emissions from permafrost.” ScienceDaily. ScienceDaily, 26 March 2018. <www.sciencedaily.com/releases/2018/03/180326160953.htm>.

ACRP Blog Interviews Target Health on the Paperless Clinical Trial

 

As a followup to an ACRP Webinar on March 7, entitled: “Regulatory Concerns When Running Paperless Clinical Trials,“ presented by Jonathan Helfgott, formerly of FDA and Jules Mitchel, President of Target Health Inc., Michael Causey, of the ACRP Blog interviewed Dr. Mitchel. The interview is entitled “Paperless Clinical Trials Gain Momentum.“ We were told that this was one of the most popular webinars with over 350 attendees.

 

If you want a copy of the slides, just let us know.

 

For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 165). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.

 

Joyce Hays, Founder and Editor in Chief of On Target

Jules Mitchel, Editor

 

QUIZ

Filed Under News | Leave a Comment

Diabetes Gene That Causes Low and High Blood Sugar Levels

The fluctuation of blood sugar (red) and the sugar-lowering hormone insulin (blue) in humans during the course of a day with three meals. One of the effects of a sugar-rich vs a starch-rich meal is highlighted.

Graphic credit: Jakob Suckale, Michele Solimena – Solimena Lab and Review Suckale Solimena 2008 Frontiers in Bioscience PMID 18508724, preprint PDF from Nature Precedings, original data: Daly et al. 1998 PMID 9625092, CC BY 3.0, https://en.wikipedia.org/w/index.php?curid=24016521

 

 

Diabetes mellitus (DM), commonly referred to as diabetes, is a group of metabolic disorders in which there are high 1) ___ sugar levels over a prolonged period. Symptoms of high blood sugar include frequent urination, increased thirst, and increased hunger. If left untreated, diabetes can cause many complications. Acute complications can include diabetic ketoacidosis, hyperosmolar hyperglycemic state, or death. Serious long-term complications include cardiovascular disease, stroke, chronic kidney disease, foot ulcers, and damage to the eyes. Diabetes is due to either the pancreas not producing enough insulin or the cells of the body not responding properly to the insulin produced. There are three main types of diabetes mellitus:

 

Type 1 DM results from the pancreas’s failure to produce enough 2) ___. This form was previously referred to as “insulin-dependent diabetes mellitus“ (IDDM) or “juvenile diabetes“. The cause is unknown.

 

Type 2 DM begins with insulin resistance, a condition in which cells fail to respond to insulin properly. As the disease progresses a lack of insulin may also develop. This form was previously referred to as “non insulin-dependent diabetes mellitus“ (NIDDM) or “adult-onset diabetes“. The most common cause is excessive body 3) ___ and insufficient exercise.

 

Gestational diabetes is the third main form, and occurs when pregnant women without a previous history of diabetes develop high blood sugar levels.

 

Prevention and treatment involve maintaining a healthy diet, regular physical exercise, a normal body weight, and avoiding use of tobacco. Control of blood pressure and maintaining proper foot care are important for people with the disease. Type 1 DM must be managed with insulin injections. Type 2 DM may be treated with medications with or without insulin. Insulin and some oral medications can cause low blood sugar. Weight loss surgery in those with obesity is sometimes an effective measure in those with type 2 DM. Gestational diabetes usually resolves after the birth of the 4) ___. As of 2015, an estimated 415 million people had diabetes worldwide, with type 2 DM making up about 90% of the cases. This represents 8.3% of the world’s 5) ___ population. As of 2014, trends suggested the rate would continue to rise. Diabetes at least doubles a person’s risk of early 6) ___. From 2012 to 2015, approximately 1.5 to 5.0 million deaths each year resulted from diabetes. The global economic cost of diabetes in 2014 was estimated to be US$612 billion. In the United States, diabetes cost $245 billion in 2012.

 

A recent, perhaps hopeful, study of families with rare blood sugar conditions has revealed a new gene thought to be critical in the regulation of insulin, the key 7) ___ in diabetes. The research carried out at two British universities: Queen Mary University of London, University of Exeter and in the U.S.. Vanderbilt University, and published in the journal PNAS, could lead to the development of novel treatments for both rare and common forms of diabetes. In addition to the more common forms of diabetes (type 1 or type 2), in about 1-2 per cent of cases diabetes is due to a genetic disorder. A defective gene typically affects the function of insulin-producing cells in the pancreas, known as beta cells. The research team studied the unique case of a family where several individuals suffer from diabetes, while other family members had developed insulin-producing tumors in their pancreas. These tumors, known as insulinomas, typically cause low blood sugar levels, in contrast to diabetes which leads to high blood sugar levels. The authors were initially surprised about the association of two apparently contrasting conditions within the same families — diabetes which is associated with high blood sugar and insulinomas associated with low blood sugar. The research shows that, surprisingly, the same 8) ___ defect can impact the insulin-producing beta cells of the pancreas to lead to these two opposing medical conditions. The team also observed that males were more prone to developing diabetes, while insulinomas were more commonly found in females, but the reasons behind this difference are still unknown.

 

The researcher team identified a genetic disorder in a gene called MAFA, which controls the production of insulin in beta 9) ___. Unexpectedly, this gene defect was present in both the family members with diabetes and those with insulinomas, and was also identified in a second, unrelated family with the same unusual dual picture. This is the first time a defect in this gene has been linked with a disease. The resultant mutant protein was found to be abnormally stable, having a longer life in the cell, and therefore significantly more abundant in the beta cells than its normal version. The authors commented that they believe that this gene defect is critical in the development of the disease and that they are now performing further studies to determine how this defect can, on the one hand, impair the production of insulin to cause diabetes, and on the other, cause insulinomas. The team stated that they are committed to understanding more about the causes of all types of 10) ___ and that this research provides important insights into the impact a change in this particular gene has on insulin-producing beta cells and how this relates to the development of a rare genetic form of diabetes. It’s also a great example of how studying rarer conditions could help us learn more about more common types of diabetes.“

 

The study was funded by Diabetes UK, while co-authors also got support from the UK National Institute of Health Research (NIHR), and the US National Institutes of Health, Wellcome Trust and Royal Society. Story Sources: Queen Mary University of London: researchers: Donato Iacovazzo, Sarah E. Flanagan, Emily Walker, Rosana Quezado, Fernando Antonio de Sousa Barros, Richard Caswell, Matthew B. Johnson, Matthew Wakeling, Michael Brandle, Min Guo, Mary N. Dang, Plamena Gabrovska, Bruno Niederle, Emanuel Christ, Stefan Jenni, Bence Sipos, Maike Nieser, Andrea Frilling, Ketan Dhatariya, Philippe Chanson, Wouter W. de Herder, Bjorn Konukiewitz, Gunter Kloppel, Roland Stein, Marta Korbonits, Sian Ellard. MAFAmissense mutation causes familial insulinomatosis and diabetes mellitus. Proceedings of the National Academy of Sciences, 2018; 201712262 DOI: 10.1073/pnas.1712262115

Queen Mary University of London. “Diabetes gene found that causes low and high blood sugar levels in the same family.“ ScienceDaily.com (15 January 2018); Wikipedia)

 

ANSWERS: 1) blood; 2) insulin; 3) weight; 4) baby; 5) adult; 6) death; 7) hormone; 8) gene; 9) cells; 10) diabetes

 

Robert Daniel Lawrence MD (1892-1968)

Robert Daniel Lawrence MD

Photo credit: Unknown – http://wellcomeimages.org/indexplus/image/L0000433.html, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=35452965

  

Dr. Robert “Robin“ Daniel Lawrence (1892 – 1968) MA, MB ChB (Hons), MD, FRCP, LLD was a British physician at King’s College Hospital, London. He was diagnosed with diabetes in 1920 and became an early recipient of insulin injections in the UK in 1923. He devoted his professional life to the care of diabetic patients and is remembered as the founder of the British Diabetic Association. Dr. Lawrence, better known as Robin Lawrence was born at 10 Ferryhill Place, Aberdeen, Scotland. He was the second son of Thomas and Margaret Lawrence. His father was a prosperous brush manufacturer, whose firm supplied all the brushes to Queen Victoria and her heirs at Balmoral.

 

At eighteen, Lawrence matriculated at Aberdeen University to take an MA in French and English. After graduation, he briefly worked in an uncle’s drapery shop in Glasgow but gave this up after just a few weeks, returning to Aberdeen where he enrolled back at Aberdeen University to study medicine. He had a brilliant undergraduate career winning gold medals in Anatomy, Clinical Medicine and Surgery and graduated ?with honors’ in 1916. During his second year, on the advice of his anatomy professor he sat and passed the primary FRCS examination in London. He gave up rugby as a student, but represented the University at both hockey and tennis. He was also President of the Students’ Representative Council. On graduation he immediately joined the RAMC and after six months home service, served on the Indian Frontier until invalided home in 1919 with dysentery and was discharged with the final rank of Captain. After a few weeks convalescing at home and fishing, he went to London and obtained the post of House Surgeon in the Casualty Department at King’s College Hospital. Six months later, now being accepted as a “King’s Man“, he became an assistant surgeon in the Ear, Nose and Throat Department. Shortly afterwards, while practicing for a mastoid operation on a cadaver, he was chiseling the bone when a bone chip flew into his right eye setting up an unpleasant infection. He was hospitalized but the infection failed to settle and he was discovered to have diabetes. At his age at this time this represented a death sentence.

 

Lawrence was initially controlled on a rigid diet and the eye infection settled but left permanently impaired vision in that eye. He abandoned thoughts of a career in surgery and worked in the King’s College Hospital Chemical Pathology Department under a Dr G A Harrison. Despite his gloomy prognosis and ill-health he managed to conduct enough research to write his MD thesis. A little later, in the expectation that he had only a short time to live, and not wishing to die at home causing upset to his family, he moved to Florence and set up in practice there. In the winter of 1922-23 his diabetes deteriorated badly after an attack of bronchitis and the end of his life seemed imminent. In early 1922, Banting, Best, Collip and Macleod in Toronto, Canada made the discovery and isolation of insulin. Supplies were initially in short supply and slow to reach the UK, but in May 1923, Harrison cabled Lawrence – “I’ve got insulin – it works – come back quick“. By this time Lawrence was weak and disabled by peripheral neuritis and with difficulty drove across the continent and reached King’s College Hospital on 28 May 1923. After some preliminary tests he received his first insulin injection on 31 May. His life was saved and he spent two months in hospital recovering and learning all about insulin. He was then appointed Chemical Pathologist at King’s College Hospital and devoted the rest of his life to the care and welfare of diabetic patients.

 

Dr. Lawrence developed one of the earliest and largest diabetic clinics in the country and in 1931 was appointed assistant physician-in-charge of the diabetic department at King’s College Hospital, becoming full physician-in-charge in 1939. He also had a large private practice. He wrote profusely on his subject and his books The Diabetic Life and The Diabetic ABC, did much to simplify treatment for doctors and patients. The Diabetic Life was first published in 1925 and became immensely popular, extending to 14 editions and translated into many languages. He published widely on all aspects of diabetes and its management, producing some 106 papers either alone or with colleagues, including important publications on the management of diabetic coma, on the treatment of diabetes and tuberculosis and on the care of pregnancy in diabetics. In 1934, he conceived the idea of an association which would foster research and encourage education and welfare of patients. To this end a group of doctors and diabetics met in the London home of Lawrence’s patient, H. G. Wells, the scientist and writer, and the Diabetic Association was formed. When other countries followed suit it became the British Diabetic Association (the BDA). Lawrence was Chairman of the Executive Council from 1934-1961 and Hon. Life President from 1962.

 

Dr. Lawrence’s enthusiasm and drive ensured the life and steady growth of this association which soon became the voice of the diabetic population and constantly sought to promote the welfare of diabetics. There are now active branches through the country. He was also a prime mover in production of “The Diabetic Journal“ (forerunner of Balance), the first issue of which appeared in January 1935. Many articles thereafter were contributed by himself anonymously. He and colleague Joseph Hoet were the main proponents in founding the International Diabetes Federation and he served as their first president from 1950-1958. At their triennial conferences, Lawrence’s appearance was always greeted with acclaim. Almost immediately after his retirement, he suffered a stroke but his spirit remained indomitable and he continued seeing private patients to the end. His last publication was an account of how hypoglycemia exaggerated the signs of his hemiparesis. Although he preached strict control of diabetes for his patients, he did not keep to a strict diet himself taking instead supplementary shots of soluble insulin as he judged he needed them. He died at home in London on 27 August 1968 aged 76.

 

Lawrence was Oliver-Sharpey lecturer at the Royal College of Physicians of London in 1946. His lecture was one of the earliest descriptions and detailed study of the rare condition now known as Lipoatrophic Diabetes. He was recipient of the Banting Medal of the American Diabetes Association the same year; Banting Lecturer of the BDA in 1949 and in 1964 Toronto University conferred on him its LLD “honoris causa.“ Charles Best, then professor of physiology in Toronto, was probably the proposer for this honor as he had met and become friendly with Lawrence when doing postgraduate research in London with Sir Henry Dale and A. V. Hill in 1925-28. They remained lifelong friends meeting regularly when in each other’s country.

 

RD Lawrence is commemorated by an annual Lawrence lecture given by a young researcher in the field of diabetes to the Medical & Scientific Section of the BDA and by the Lawrence Medal awarded to patients who have been on insulin for 60 years or more. The BDA, now Diabetes UK remains his lasting memorial.

 

Immune Cells in the Retina Can Spontaneously Regenerate

 

The retina is a thin layer of cells in the back of the eye that includes light-sensing photoreceptor cells and other neurons involved in transmitting visual information to the brain. Mixed in with these cells are microglia, specialized immune cells that help maintain the health of the retina and the function of retinal neurons. Microglia are also present in other parts of the central nervous system, including the brain. In a healthy retina, communication between neurons and microglia is important for maintaining the neuron’s ability to send signals to the brain. When the retina is injured, however, microglia have an additional role: They migrate quickly to the injury site to remove unhealthy or dying cells. However, they can also remove healthy cells, contributing to vision loss. Studies show that in degenerative retinal disorders like age-related macular degeneration (AMD) and retinitis pigmentosa (RP), inhibiting or removing microglia can help retain photoreceptors, and thus slow vision loss. But return of microglia is still important to support the retina’s neurons.

 

According to an article published online in Science Advances (21 March 2018), microglia can completely repopulate themselves in the retina after being nearly eliminated. The cells also re-establish their normal organization and function. The findings point to potential therapies for controlling inflammation and slowing progression of rare retinal diseases such as RP and AMD, the most common cause of blindness among Americans 50 and older.

 

The authors were interested in understanding what happens in the retina after microglia have been eliminated, particularly whether the cells could return to their normal arrangement and fulfill their normal functions. To test this, they depleted the microglia in the retinas of mice using the drug PLX5622 (Plexxikon), which blocks the microglial CSF-1 receptor. Microglia depend on continuous signals through this receptor for survival. Interruption of this signaling for several days caused the microglia to nearly disappear, leaving just a few cells clustered around the optic nerve — the cable-like bundle of nerve fibers that carries signals from the retina to the brain. Since loss of microglia for a short time doesn’t affect the function of neurons, removing microglia temporarily — in order to reduce inflammation for example — could potentially be useful as a therapeutic intervention for degenerative or inflammatory disorders of the retina.

 

Within 30 days after stopping the drug, the authors found that the microglia had repopulated the retina, returning to normal density after 150 days. Using a novel method for visually tracking microglial movements in the retina, they determined that the returning microglia initially grew in clusters near where the optic nerve leaves the eye. Gradually, new microglia expanded outwards towards the edges of the retina. Over time, the cells re-established an even distribution across and through the various layers of the retina.

 

To test whether the new microglia were fully functional, the authors used an injury model where photoreceptor cells are damaged by bright light. The new microglia were able to activate and migrate to the injury site normally. In addition, using electroretinography (ERG), a technique that measures the electrical signals generated by retinal neurons after being stimulated with light, the researchers tested the health of different groups of neurons. They found that the microglia were able to communicate with and fully maintain the function of neurons in the retina, especially when the depletion was short-lived.

 

Drugs that remove microglia are now administered systemically, affecting the brain and other parts of the central nervous system. According to the authors, more research is needed to find ways to administer these drugs directly to the retina, sparing off-target tissues.

 

New Genetic Mutation Link to ALS

 

KIF5A regulates part of the kinesin family of proteins that serve as tiny intracellular motors. Problems with these proteins are connected to amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, Parkinson’s disease and Alzheimer’s disease. KIF5A mutations were previously known to be connected to two other rare neurodegenerative diseases with muscle weakening, stiffening and spasticity symptoms similar to ALS: hereditary spastic paraplegia type 10 (SPG10) and Charcot-Marie-Tooth Type 2 (CMT2.) Scientists suspected KIF5A might be associated with ALS but lacked definite proof until now.

 

Now, according to an article published in Neuron (21 March 2018), Kinesin family member 5A (KIF5A), has been definitively connected to ALS. The findings identify how mutations in KIF5A disrupt transport of key proteins up and down long, threadlike axons that connect nerve cells between the brain and the spine, eventually leading to the neuromuscular symptoms of ALS.

 

According to the NIH, it took a comprehensive, collaborative effort to analyze a massive amount of genetic data to pin down KIF5A as a suspect for ALS. To zero in on KIF5A, the NIH team performed a large-scale genome-wide association study, while the University of Massachusetts team concentrated on analyzing rare variants in next generation sequence data. Over 125,000 samples were used in this study, making it by far the largest such study of ALS performed to date.

 

According to the authors, axons extend from the brain to the bottom of the spine, forming some of the longest single cellular pathways in the body, and that KIF5A helps to move key proteins and organelles up and down that axonal transport system, controlling the engines for the nervous system’s long-range “cargo trucks.“ This mutation disrupts that system, causing the symptoms we see with ALS. The authors cautioned that the discovery, while exciting, still leaves much more work to be done. The authors added that next steps for the project include further study of the frequency and location of mutations within KIF5A and determining what cargos are being disrupted.

 

Device Cleared That Senses Optimal Time to Check Intraocular Pressure

 

Elevated IOP is often associated with the optic nerve damage that is characteristic of glaucoma, the leading cause of vision loss that affects an estimated 3 million Americans.. Many patients have no symptoms until significant vision has been lost, and this loss is irreversible. intraocular pressure (IOP) varies throughout the day and may not be abnormally high when the patient is at an eye care professional’s office having an eye exam. For example, it is common for IOP to increase during sleep when the patient is lying down.

 

The FDA has allowed marketing of a one-time use contact lens that may help practitioners identify the best time of day to measure a patient’s intraocular pressure (IOP). The Triggerfish has a sensor embedded in a soft silicone contact lens that detects tiny changes or fluctuations in an eye’s volume. The device is worn for a maximum of 24 hours, transmitting data wirelessly from the sensor to an adhesive antenna worn around the eye. A portable data recorder worn by the patient receives information from the antenna and can transfer the data via Bluetooth to the clinician’s computer, which shows the range of time during the day the pressure of the eye may be increasing. The device does not actually measure IOP and is not intended to be a diagnostic tool.

 

The Triggerfish is indicated for use in adults age 22 and older under the direction and supervision of a health care professional. Clinical data supporting the marketing authorization of the Triggerfish included several studies of the safety and tolerability of the contact lenses and the effectiveness of the device measurement. The effectiveness of the device was demonstrated by showing an association between the Triggerfish device output and IOP fluctuation. The most common temporary side effects were pressure marks from the contact lens, ocular hyperemia (red eyes) and punctate keratitis (irritation of the cornea). The FDA reviewed the data for the Triggerfish through the de novo premarket review pathway, a regulatory pathway for some low- to moderate-risk medical devices that are not substantially equivalent to an already legally-marketed device.

 

The Triggerfish is manufactured by Sensimed AG of Lausanne, Switzerland.

 

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