Marrow Christmas And A Happy New Smear!

Estrogen Alters Memory Circuit Function in Women with Gene Variant

Fluctuations in estrogen can trigger atypical functioning in a key brain memory circuit in women with a common version of a gene, NIMH scientists have discovered. Brain scans revealed altered circuit activity linked to changes in the sex hormone in women with the gene variant while they performed a working memory task.

(Image caption: Both PET scans (left) and fMRI scans (right) showed the same atypical activation (yellow) in the brain’s memory hub, or hippocampus, in response to estrogen in women performing a working memory task – if they carried a uniquely human version of the BDNF gene. Activity in this area is typically suppressed during working memory. Picture shows PET and fMRI data superimposed over anatomical MRI image)

The findings may help to explain individual differences in menstrual cycle and reproductive-related mental disorders linked to fluctuations in the hormone. They may also shed light on mechanisms underlying sex-related differences in onset, severity, and course of mood and anxiety disorders and schizophrenia. The gene-by-hormone interaction’s effect on circuit function was found only with one of two versions of the gene that occurs in about a fourth of white women.

Drs. Karen Berman, Peter Schmidt, Shau-Ming Wei, and colleagues, of the NIMH Intramural Research Program, report on this first such demonstration in women April 18, 2017 in the journal Molecular Psychiatry.

Prior to the study, there was little evidence from research on the human brain that might account for individual differences in cognitive and behavioral effects of sex hormones. For example, why do some women develop postpartum depression and others do not – in response to the same hormone changes? Why do some women report that estrogen replacement improved their memory, whereas large studies of postmenopausal estrogen therapy show no overall improvement in memory performance?

Evidence from humans has also been lacking for the neural basis of stark sex differences in prevalence and course of mental disorders that are likely related to sex hormones. For example, why are there higher rates of mood disorders in females and higher rates of ADHD in males – or later onset of schizophrenia in females?

In seeking answers to these questions, the researchers focused on working memory, a well-researched brain function often disturbed in many of these disorders. It was known that working memory is mediated by a circuit from the brain’s executive hub, the prefrontal cortex, to its memory hub, the hippocampus. Notably, hippocampus activity is typically suppressed during working memory processing.

Following-up on a clue from experiments in mice, the NIMH team hypothesized that estrogen tweaks circuit function by interacting with a uniquely human version of the gene that codes for brain derived neurotrophic factor (BDNF), a pivotal chemical messenger operating in this circuit. To find out, the researchers experimentally manipulated estrogen levels in healthy women with one or the other version of the BDNF gene over a period of months. Researchers periodically scanned the women’s brain activity while they performed a working memory task to see any effects of the gene-hormone interaction on circuit function.

The researchers first scanned 39 women using PET (positron emission tomography) and later confirmed the results in 27 women using fMRI (functional magnetic resonance imaging). Both pegged atypical activity in the hippocampus to the interaction. Turning up the same findings using two types of neuroimaging strengthens the case for the accuracy of their observations, say the researchers. Such gene-hormone interactions affecting thinking and behavior are consistent with findings from animal studies and are suspect mechanisms conferring risk for mental illness, they add.

Toxic Alzheimer’s Protein Spreads Through Brain Via Extracellular Space

A toxic Alzheimer’s protein can spread through the brain—jumping from one neuron to another—via the extracellular space that surrounds the brain’s neurons, suggests new research from Karen Duff, PhD, and colleagues at Columbia University Medical Center.

(Image caption: Orange indicates where tau protein has traveled from one neuron to another. Credit: Laboratory of Karen Duff, PhD)

The spread of the protein, called tau, may explain why only one area of the brain is affected in the early stages of Alzheimer’s but multiple areas are affected in later stages of the disease.

“By learning how tau spreads, we may be able to stop it from jumping from neuron to neuron,” says Dr. Duff. “This would prevent the disease from spreading to other regions of the brain, which is associated with more severe dementia.”

The idea the Alzheimer’s can spread through the brain first gained support a few years ago when Duff and other Columbia researchers discovered that tau spread from neuron to neuron through the brains of mice.

In the new study, lead scientist Jessica Wu, PhD, of the Taub Institute discovered how tau travels by tracking the movement of tau from one neuron to another. Tau, she found, can be released by neurons into extracellular space, where it can be picked up by other neurons. Because tau can travel long distances within the neuron before its release, it can seed other regions of the brain.

“This finding has important clinical implications,” explains Dr. Duff. “When tau is released into the extracellular space, it would be much easier to target the protein with therapeutic agents, such as antibodies, than if it had remained in the neuron.”

A second interesting feature of the study is the observation that the spread of tau accelerates when the neurons are more active. Two team members, Abid Hussaini, PhD, and Gustavo Rodriguez, PhD, showed that stimulating the activity of neurons accelerated the spread of tau through the brain of mice and led to more neurodegeneration.

Although more work is needed to examine whether those findings are relevant for people, “they suggest that clinical trials testing treatments that increase brain activity, such as deep brain stimulation, should be monitored carefully in people with neurodegenerative diseases,” Dr. Duff says.

Using the Power of Space to Fight Cancer

From cancer research to DNA sequencing, the International Space Space is proving to be an ideal platform for medical research. But new techniques in fighting cancer are not confined to research on the space station. Increasingly, artificial intelligence is helping to “read” large datasets. And for the past 15 years, these big data techniques pioneered by our Jet Propulsion Laboratory have been revolutionizing biomedical research.

Microgravity Research on Space Station

On Earth, scientists have devised several laboratory methods to mimic normal cellular behavior, but none of them work exactly the way the body does. Beginning more than 40 years ago aboard Skylab and continuing today aboard the space station, we and our partners have conducted research in the microgravity of space.  In this environment, in vitro cells arrange themselves into three-dimensional groupings, or aggregates. These aggregates more closely resemble what actually occurs in the human body. Cells in microgravity also tend to clump together more easily, and they experience reduced fluid shear stress – a type of turbulence that can affect their behavior. The development of 3D structure and enhanced cell differentiation seen in microgravity may help scientists study cell behavior and cancer development in models that behave more like tissues in the human body.

In addition, using the distinctive microgravity environment aboard the station, researchers are making further advancements in cancer therapy. The process of microencapsulation was investigated aboard the space station in an effort to improve the Earth-based technology. Microencapsulation is a technique that creates tiny, liquid-filled, biodegradable micro-balloons that can serve as delivery systems for various compounds, including specific combinations of concentrated anti-tumor drugs. For decades, scientists and clinicians have looked for the best ways to deliver these micro-balloons, or microcapsules, directly to specific treatment sites within a cancer patient, a process that has the potential to revolutionize cancer treatment.

A team of scientists at Johnson Space Center used the station as a tool to advance an Earth-based microencapsulation system, known as the Microencapsulation Electrostatic Processing System-II (MEPS-II), as a way to make more effective microcapsules. The team leveraged fluid behavior in microgravity to develop a new technique for making these microcapsules that would be more effective on Earth. In space, microgravity brought together two liquids incapable of mixing on Earth (80 percent water and 20 percent oil) in such a way that spontaneously caused liquid-filled microcapsules to form as spherical, tiny, liquid-filled bubbles surrounded by a thin, semipermeable, outer membrane. After studying these microcapsules on Earth, the team was able to develop a system to make more of the space-like microcapsules on Earth and are now performing activities leading to FDA approval for use in cancer treatment.  

In addition, the ISS National Laboratory managed by the Center for the Advancement of Science in Space (CASIS) has also sponsored cancer-related investigations.  An example of that is an investigation conducted by the commercial company Eli Lilly that seeks to crystallize a human membrane protein involved in several types of cancer together with a compound that could serve as a drug to treat those cancers. 

“So many things change in 3-D, it’s mind-blowing – when you look at the function of the cell, how they present their proteins, how they activate genes, how they interact with other cells,” said Jeanne Becker, Ph.D., a cell biologist at Nano3D Biosciences in Houston and principal investigator for a study called Cellular Biotechnology Operations Support Systems: Evaluation of Ovarian Tumor Cell Growth and Gene Expression, also known as the CBOSS-1-Ovarian study. “The variable that you are most looking at here is gravity, and you can’t really take away gravity on Earth. You have to go where gravity is reduced.“ 

Crunching Big Data Using Space Knowledge

Our Jet Propulsion Laboratory often deals with measurements from a variety of sensors – say, cameras and mass spectrometers that are on our spacecraft. Both can be used to study a star, planet or similar target object. But it takes special software to recognize that readings from very different instruments relate to one another.

There’s a similar problem in cancer research, where readings from different biomedical tests or instruments require correlation with one another. For that to happen, data have to be standardized, and algorithms must be “taught” to know what they’re looking for.

Because space exploration and cancer research share a similar challenge in that they both must analyze large datasets to find meaning, JPL and the National Cancer Institute renewed their research partnership to continue developing methods in data science that originated in space exploration and are now supporting new cancer discoveries.

JPL’s methods are leading to the development of a single, searchable network of cancer data that researcher can work into techniques for the early diagnosis of cancer or cancer risk. In the time they’ve worked together, the two organizations’ efforts have led to the discovery of six new Food and Drug Administration-approved cancer biomarkers. These agency-approved biomarkers have been used in more than 1 million patient diagnostic tests worldwide.

Quote from #JaneGoodall primatologist and anthropologist. More quotes like this to inspire you in my new journal I Love Science, in stores March but ready for preorder now! #womeninscience #ilovescience #anthropology #scientificliteracy

Neural Pathways by Alexey Kashpersky

Network Lost

If you believe the theory of six degrees of separation, we’re all connected to each other (and possibly to Kevin Bacon) by common friends and friend-of-friends. It might feel like a small world – in fact, these patterns crops up in all sorts of places. Small world networks connect distant brain cells, and help these lymph nodes (outlined in grey) fight infections. A network of fibroblastic reticular cells (FRCs, red) spreads out inside each node, producing chemicals (green) to support immune cells while they zip around the node gathering antigens – chemical information used to target bacteria. These mouse lymph nodes are treated with different doses of a toxin that destroys FRC networks. A high dose crumples the lymph node in the bottom right. Amazingly, many of these networks repair themselves, showing just how committed immune defences are to keeping their small worlds alive.

Written by John Ankers

Image from work by Mario Novkovic, Lucas Onder and Jovana Cupovic, and colleagues

Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland

Image originally published under a Creative Commons Licence (BY 4.0)

Published in PLOS Biology, July 2016

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Crystals of the female hormone oxytocin

In women this hormone is secreted naturally by the pituitary gland. Oxytocin causes contractions of the uterus during labour, and it also stimulates the flow of milk in women who are breast-feeding.

Last Week In Science

1. Broad Institute wins CRISPR patent battle

basically UC Berkely has rights to use CRISPR in “all kinds of cells” and Broad has rights in “eukaryotic cells” (yay legal system). Anticipate more legal battles since there are more types of CRISPR techniques

2. Human genome editing gets the OK to prevent “serious heritable diseases and conditions only” 

Bioshock likely to happen in 50 years as “serious disease” dwindles in to “mediocre disease” and finally “what the hell let’s shoot fire from our hands”

3. With the EPA at risk of being destroyed, what was life like before the EPA?

4. Congress wants to shift Earth Science away from NASA (and focus on deep space)

4.1 Coders continue to save climate data

5. This years winners of underwater photos

6. Got trash on your power lines? That’s alright just attach a flamethrower to a drone, no worries 

7. Fungicides bring us closer to figuring out why all of the bees are dying

7.1 (but who cares right? we can just make quadcopters do all the work)

8. Australia is HOT AS BALLS

9. Aztecs probably died off from salmonella outbreak

10. Our genetic past and present sanitary world lead to increased autoimmunity and allergy

10.1 Getting the right microbiome early on is so important for health

11. New Zealand on a new continent might make maps include it more often

12. Now you realize how slow the speed of light is on a cosmic scale

13. Meta-Analysis shows Vitamin D supplementation provides “modest protective effect” from respiratory infections like the flu or cold

14. Watch Yosemite’s Horsetail and its annual “FireFall” (image via Robert Minor)

15. Trump’s press conference makes people wonder if he is mentally ill and if we should start testing old ass presidents for dementia

16. He continue’s to spew more anti-vaccine bullshit, showing his ignorance of science and RFK Jr.’s scam needs “just one study” to change his mind

16.1 more than 350 organizations write to Trump to assure his feeble mind that vaccines are safe

17. Simple fractal patterns are key to Rorschach test

18. Imagine shining a light somewhere on your body and microscopic bots deliver drugs there

19. How flat can a planet be?

20. Triangulene created for the first time

Who needs carefully planned chemical reactions when you can just blast hydrogens off with electricity?

21. All of the nerdy. Valentine’s. you. will. ever. need. 

22. Help find Planet 9 in your spare time

22.1 Don’t have time? then do science while your computer is idle!

Vexing Virus Shields

Around 36 million people worldwide have HIV. Scientists are trying to develop an HIV vaccine using antibodies, molecules our bodies make to target and tag invading particles. Researchers have found that rabbits exposed to a strain of HIV produce antibodies targeting a specific part of the virus: a hole in its glycan shield. This shield consists of sugar molecules attached to the outside of the virus, protecting it from attack – the hole is thus a gap in its defences. However, although most HIV strains have a hole in their glycan shields, not many strains have one in the same position as was identified, so different antibodies would need to be developed. The image shows how much certain parts of the glycan shield are conserved between different HIV strains – red being 90–100%, and green 50–60%. This is a step towards vaccines, but the shield remains a challenge in vaccine development.

Written by Esther Redhouse White

Image by Sergey Menis, Laura McCoy and James Voss

The Scripps Research Institute, USA and University of Amsterdam, The Netherlands

Image copyright held by original authors

Research published in Cell Reports, August 2016

Published in eLife, June 2016

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The Blue Lava of Kawah Ijen Volcano. The ‘blue lavas’ are a rare phenomenon, only visible on the Kawah Ijen Volcano, in Indonesia. It may look like the volcano is spewing blue lava, but in fact, the shocking blue fire occurs when the volcanic sulphuric gases combust. Emerging from cracks in the volcano’s side, these gases ignite when coming into contact with air. It’s not actual blue lava, but blue flames. (video)