Tuesday
Jan242017

Well-formed cerebellum found in ovaries of a 16-year old girl

Have you ever found something to be really scary but simultaneously very interesting? I had that weird feeling while reading an article about a patient’s teratomas exhibiting a well-formed cerebellum and brainstem-like structures, published by a group from the Nara Medical University Japan this year in January.

Arising from three embryonic germ layers, a teratoma (greek for “monstrosity”) is a neoplasm forming different kinds of tissue, such as organs, hair and teeth or even brain tissue. As they are derived from primitive, pluripotent stem cells, teratomas belong to the class of germ cell tumors (GCTs). One can distinguish between either cancerous or non-cancerous GCTs that happen to occur in the ovary or testes. As the formation of these tissues seems to be very controlled, the tissue components in teratomas often show well-differentiated and highly organized structures. One extreme example was the case of a 16-year-old Japanese girl who was found to have large, predominantly cystic tumors in both of her ovaries that included a well-formed cerebellum and brainstem-like structures. The first of the two teratomas contained a small amount of CNS tissue without well-organized structures. The other one had - beneath adipose or bronchial wall tissue - mostly well-differentiated and highly organized cerebellar tissue approximately 2.8 centimeters in size. The cerebellar cortex showed well-formed layers, which are histologically very similar to those of normal adults. Interestingly, the thickness of the molecular layer was approximately the same as a normal adults’ and immunohistochemistry could prove many parallel fibers in the lower half of the molecular layer. In addition, the authors found partial focal expansion and dysmorphic change of dendrites in Purkinje cells of the cerebellar cortex. The tumor was covered by fibrous tissue containing bone plates in a tectum-like manner.

- YEK

References:

1. Well-formed cerebellum and brainstem-like structures in a matrue ovarian teratoma: Neuropathological observations.  Shintaku, M. Sakuma, T. Ohbayashi, C. & Maruo, M. Neuropathology. 2017. doi:10.1111/neup.12360

2. Weimann, A., et al. Original-Prufungsfragen mit Kommentar GK 2. Allgemeine Pathologie, Theime Verlag, 2002, 201. [German]

3. Forrester & Merz. Paediatr Perinat Epidemiol. 2006, 20, 54-58.

4. Ng, et al., Cancer. 1999, 86, 1198-1202.

Thursday
Jan122017

Fireworks and their impact on the environment and on human health

Have you enjoyed all the fireworks on New Year’s Eve? Maybe all of us should remember this for next year: The fine dust pollution in Munich, Germany was 564 mg/m3 on New Year’s Eve – more than 14 times the maximal annual mean value of 40 mg/m3.

Fine dust pollution can – depending on their actual size – penetrate the trachea and smaller particles can even reach the lung. Fine dust pollution is associated with more respiratory diseases, exacerbation in asthmatic patients, cardiovascular problems and even lung cancer.

The chart below shows the daily mean concentration of very small particles (smaller than 2.5 mm), which are especially worrying as they readily penetrate into bronchioles and may even reach the bloodstream, in Munich in December and January with a huge peak on New Year’s Eve.

Just one more number, to put the extent of the pollution into context: Every year fireworks release about 4000 tons of fine dust in Germany (PM10 – particles smaller than 10 mm), which are equal to 15 % of all fine dust released in traffic in ONE YEAR.

On top of the possible health hazards of fine dust pollution the simple volume of fireworks can be dangerous too! Alone in Germany (I’m sorry for all the data from Germany, but I spent New Year’s there :-D) around 8000 people are suffering from damage to the inner ear each New Year’s Eve, with about one third of them suffering permanently.

Another environmental problem of fireworks is the fact, that there is still unburnt residues inside, like propellants or colorants, which in turn can pollute lakes and rivers. One exemplary residue is Perchlorate, which is associated with thyroid problems.

Maybe all of us should think about reducing our use of fireworks and instead enjoy watching all those firework explosions of our neighbors.

If you like to read something from a rather chemical perspective about greener fireworks or their ingredients, I’d recommend this article: http://www.bbc.com/future/story/20120611-greener-cleaner-fireworks

-NS

 

References:

http://www.umweltbundesamt.de/sites/default/files/medien/479/publikationen/hgp_wenn_die_luft_zum_schneiden_ist_0.pdf (in German)

http://theconversation.com/our-prettiest-pollutant-just-how-bad-are-fireworks-for-the-environment-52451

Tuesday
Jan032017

Non-invasive gamma oscillations show promise for reducing amyloid plaque

It is well established that Alzheimer’s disease (AD) is a fatal neurodegenerative disorder, which currently afflicts ~5.4 million Americans1. There are five FDA drugs approved to treat the debilitating symptoms of AD1, but no therapeutic to date can alleviate the underlying pathology. Recently, solanezumab, an experimental AD drug developed by Eli Lilly, failed to significantly slow the progression of cognitive decline in a phase 3 clinical trial2. Failure of this AD drug, and many others, is complicated by both the heterogeneity of AD and the extensive anatomical damage caused by the disease. A common hypothesis is that by the time AD symptoms emerge, neurological injury is beyond repair. To circumvent these issues, ideal AD treatments would be non-toxic, non-invasive, and prophylactic.
A recent report from Iaccarino and Singer et al. identified a non-invasive light-based intervention to reduce Aβ plaque formation (a hallmark of AD pathology) in AD mouse models3. This study established a link between gamma waves (a particular type of neural oscillation) and AD-related neurotoxicity. First, the authors determined that gamma waves were reduced in the hippocampus of pre-symptomatic AD mice (5XFAD model) as compared to wild-type controls, through electrophysiological recordings. To better understand the function of gamma waves, mice were engineered using optogenetics to produce 40 hertz (Hz) gamma oscillations upon pulses of light in a specific region of the brain (fast-spiking parvalbumin interneurons). One hour of gamma wave production was sufficient to reduce Aβ protein levels by ~40% as determined by enzyme-linked immunosorbent assays (ELISA) and immunohistochemistry (IHC). Next, authors investigated gene expression profiles altered by gamma wave production through RNA sequencing. Interestingly, genes associated with the engulfing state of microglia (immune cells of the brain) were enriched. As determined by IHC, microglia were enlarged and co-localized with Aβ plaques, suggesting that gamma waves stimulated microglial-mediated phagocytosis of Aβ.
To further the application of these findings, the authors engineered a 40 Hz light flickering paradigm to stimulate gamma waves in the mouse visual cortex non-invasively. Analogous to the optogenetic approach, one hour of light flicker intervention reduced Aβ protein levels in the visual cortex of AD and wild-type mice by 20-58%, as determined by ELISA. These effects were acute (lasting less than twenty-four hours) and constrained to the visual cortex (Aβ protein was not reduced in the hippocampus). In AD mice, the light flicker intervention also resulted in enlarged microglia that engulfed Aβ protein, as determined by IHC and fluorescence-activated cell sorting combined with ELISA. Finally, the authors investigated whether the light flicker intervention had utility in mice with advanced Aβ plaque formation. One hour of light flicker intervention for seven consecutive days resulted in reduction of Aβ plaque by ~67% and also reduced Tau phosphorylation (another hallmark of AD pathology).
Taken together this extensive mechanistic study provides a promising foundation for non-invasive AD treatment. Moving forward it will be important to explore the long-term effects of 40 Hz light flickering on plaque load, brain atrophy, cognition, and survival time. Future studies combining transcranial magnetic stimulation to produce 40 Hz gamma oscillations and amyloid positron emission tomography imaging in humans could further determine the in vivo relationship between gamma waves and Aβ plaque formation in AD patients.
-TMG
1) Alzheimer’s Association, http://www.alz.org/research/overview.asp, 3 November 2016.
2) New York Times, “Eli Lilly’s Experimental Alzheimer’s Drug Fails in Large Trial”,  http://www.nytimes.com/2016/11/23/health/eli-lillys-experimental-alzheimers-drug-failed-in-large-trial.html?_r=0, 3 November 2016. 
3) Iaccarino and Singer et al. (2016) Gamma frequency entrainment attenuates amyloid load and modifies microglia Nature. 
Monday
Nov282016

The Data Science Behind Cyber Monday

As you awaken from your Thanksgiving food-coma and return to the work-week grind, don’t forget: today is Cyber Monday!  The holiday-shopping season officially began last week on Black Friday, and today retailers are expected to reign in similar profits.  Forbes magazine predicts that retail sales will exceed $3 billion on both Black Friday and Cyber Monday [1].  

And in the spirit of giving this holiday season, shoppers will be handing over enormous amounts of data to every site they visit.  Behind the scenes at online retailers like Amazon are teams of data scientists tasked with pricing merchandise, targeting advertising, and predicting consumer behavior [2].  Ever notice that when you visit an online retailer and browse for an item without buying it, that item will show up in advertisements on other webpages for the next few days?  That’s a machine-learning algorithm at work, designed by data scientists.  As you browse the web, you leave a trail that can be picked up by advertisers.  So when you compare different cell-phones on Amazon, odds are you’ll start seeing ads for mobile devices in your Facebook newsfeed and in banner-ads while you’re reading the New York Times. With more data, these algorithms “learn” faster, so they actually become more efficient during the holiday-shopping rush [3]. The algorithms consider everything from the items you browsed and the stores you visited to the movement of your mouse and the number of clicks you made on a particular page.  On sites like Amazon, they’ll also consider whether you’re a Prime Member and items you’ve previously purchased.  

Thanks to Big Data and advances in machine learning, advertisers can push their products to targeted demographics like never before.  Still, this type of advertising does have some drawbacks.  The large amounts of data that companies accumulate about their shoppers could come with some security risks.  Moreover, last month Facebook came under-fire for offering the ability for advertisers in housing, employment, and credit, to target by “ethnic affinity” [4].  And in 2012, Target’s algorithms accidently exposed a teen girl’s pregnancy to her father [5].

Despite these drawbacks, advances in machine learning and data science and paving the way for new discoveries in other fields.  Similar algorithms power Siri and the Amazon Echo.  Machine learning and Big Data are revolutionizing the way we understand genetics, disease, and the human brain.  Like any new technology, machine-learning algorithms should be designed with their context in mind and implemented with care.  So as you shop this Cyber Monday, you can start by crossing one gift off your list: the gift of data that you’ll be giving to all of the retailers you visit.
-TM
[1] http://www.forbes.com/sites/shephyken/2016/11/19/2016-black-friday-cyber-monday-holiday-insights-and-predictions/#785131c5243f
[2] https://www.internetretailer.com/commentary/2016/11/12/science-behind-black-friday-and-cyber-monday-pricing
[3] http://everything-pr.com/big-data-black-friday/54064/
[4] http://www.forbes.com/sites/kathleenchaykowski/2016/11/11/facebook-to-ban-ethnic-affinity-targeting-for-housing-employment-credit-related-ads/#2980ba0ca747
[5] http://www.forbes.com/sites/kashmirhill/2012/02/16/how-target-figured-out-a-teen-girl-was-pregnant-before-her-father-did/
 

 

Wednesday
Nov232016

The science behind the food coma

Tomorrow is Thanksgiving, a day of family, football, and feasting! Following a large meal, many people experience what is known colloquially as a “food coma”.

Recently, scientists from the Scripps Research Institute, Florida Atlantic University, and Bowling Green State University may have found a reason for the phenomenon of postprandial sleep.  William Ja and colleagues used Drosophila (fruit flies) as a model to investigate the effects of eating on sleep. They found that after a meal, flies increased sleep for a short period before returning to a normal state of alertness. Flies that ate more also slept more. Protein, salt, and the amount eaten increased sleep, but sugar had no effect.

Researchers also used genetic tools to turn on and off neurons in the fly brain and identified a number of brain circuits that play a role in controlling post-meal sleepiness. Some of these respond specifically to protein consumption, while others are sensitive to the fruit fly’s circadian rhythms.

While this study was in fruit flies, there are some parallels and connections to mammals. Researchers speculate that post-meal sleep is important, perhaps for boosting digestion or helping animals form memories about a food source.

I wish you and your family a Happy Thanksgiving! Hopefully the “food coma” won’t hit too hard. 

CJW

References:

Scripps Research Institute. “Scientists Find Surprising Answers to ‘Food Coma’ Conundrum.” NeuroscienceNews. NeuroscienceNews, 22 November 2016.
http://neurosciencenews.com/food-coma-neuroscience-5578/

“Postprandial sleep mechanics in Drosophila” by Keith R Murphy, Sonali A Deshpande, Maria E Yurgel, James P Quinn, Jennifer L Weissbach, Alex C Keene, Ken Dawson-Scully, Robert Huber, Seth M Tomchik, and William W Ja in eLife. Published online November 22 2016 doi:10.7554/eLife.19334