Author Archives: NeuroJo

Brain Metabolism and Neurodegeneration Links: July 10th 2015

Oxidative stress in Alzheimer disease and mild cognitive impairment: evidence from human data provided by redox proteomics: http://link.springer.com/article/10.1007/s00204-015-1556-z

AMPK-mediated regulation of neuronal metabolism and function in brain diseases: http://informahealthcare.com/doi/abs/10.3109/01677063.2015.1067203

Influence of Lentiviral β-Synuclein Overexpression in the Hippocampus of a Transgenic Mouse Model of Alzheimer’s Disease on Amyloid Precursor Protein Metabolism and Pathology: http://www.karger.com/Article/Abstract/430952

The hitchhiker’s guide to PGC-1α isoform structure and biological functions: http://link.springer.com/article/10.1007/s00125-015-3671-z

Overexpression of PGC-1α Influences Mitochondrial Signal Transduction of Dopaminergic Neurons: http://link.springer.com/article/10.1007/s12035-015-9299-7

The Polg Mutator Phenotype Does Not Cause Dopaminergic Neurodegeneration in DJ-1: http://eneuro.org/content/eneuro/2/1/ENEURO.0075-14.2015.full.pdf

Metabolic clues to salubrious longevity in the brain of the longest-lived rodent: the naked mole-rat: http://www.ncbi.nlm.nih.gov/pubmed/25940666

Proteomic analysis and functional characterization of mouse brain mitochondria during aging reveal alterations in energy metabolism: http://www.ncbi.nlm.nih.gov/pubmed/25546256

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The wonder of pregnancy

I’m not an overjoyed pregnant woman. I guess this comes as no surprise to those that know me, as I’m not necessarily the type of person with whom ‘overjoyed’ is quickly associated. I am incredibly grateful to pregnant and deeply hope for a healthy child but the ‘wonder’ of pregnancy largely eluded me.

After the first few weeks of knowing I was pregnant, the rush of excitement and happiness wore off, and the fatigue and nausea set in. Those first few months of pregnancy felt akin to when I had undiagnosed Graves’ disease, I was tired all the time and my emotions were out of my control. Pregnancy almost felt like another chronic disease to live with. Each time I went for an ultrasound I was surprised to see that there was a living fetus in there. Feeling like crap and not being able to tell anyone why just felt like the new normal.

Even into the second trimester after we’d told people and when I started feeling less tired and nauseated I still didn’t get those feelings of wonder at pregnant. I wondered why I did not feel that wonder. It has taken until now, when at 24+ weeks pregnant, I can feel little Nugget moving around on a regular basis to get those feelings.

She has a little schedule. She usually wakes up when I do (or she’s awake beforehand I just don’t feel her as I’m asleep) then she has a bit of exercise around 11am, followed by a burst of activity around 2pm, then again around 6 in the evening and finally at bed time around 10pm.

If I’m busy working or lost in thought she’ll kick me in the uterus it really does bring home the wonder of it all.

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When your research keeps being overlooked

Twice in the past two days I’ve read sentences similar to this one implying that increased levels of the protein that shall be referred to as ‘X’ to avoid getting too specialized, is protective in models of Parkinson’s disease (PD):

“X mRNA levels are reduced in a number of neurodegenerative diseases …. since increased levels ameliorate behavioral defects and neuropathology of Huntington’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis”. 

The thing is that two papers published in 2012 showed that increased levels of X did not ameliorate the neuropathology of PD and actually caused some PD-like symptoms in model animals, like depletion of dopamine (that’s a big one). I was the first author of one of these papers and Carine Ciron from the EPFL was the other (1). Neither of these papers were cited in either article that referred to increased ‘X’ being protective against PD.

The issue is possibly clouded by one paper demonstrating that normalization of X levels rescued striatal pathology in a knockout model (2) and another showing that transgenic mice overexpressing X (without characterization of the level of expression) displayed increased resistance to the PD-inducing toxin MPTP (3).

In another example, I also recently read a review article where the authors mentioned all of the supporting evidence for increased levels of another protein (Y?) after exercise in humans and cited none of the studies demonstrating that this protein wasn’t increased after exercise.

This process of selective citation then becomes self-reinforcing as readers of those articles assume that the authors have done a good job in citing the literature and then often go on to cite the same papers without further thought or research.

There are a number of possible reasons why certain citations are left out. Journals have space limitations and that in many cases it is not possible to cite all of the relevant literature, however at the moment there are there are very few papers in either the X or Y field.

Also, people can be biased towards the literature that supports their theories (and the current trend for ‘hypothesis-driven’ rather than ‘exploratory’ research may have a hand in this) but as scientists we have a duty to be objective, present all aspects, and to not get too attached to our pet hypotheses.

Finally, sometimes people just lose track of the current literature, or a paper flies under the radar due to inappropriate cataloging or lack of promotion by the authors. However, with services such as Google Scholar, Pubcrawler and Citeulike that will deliver the relevant citations to your inbox or a daily, weekly or monthly basis, not citing the most relevant literature can come across as lazy or biased.

1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3313800/

2. http://www.sciencedirect.com/science/article/pii/S0092867406012281

3. http://link.springer.com/article/10.1007%2Fs00018-011-0850-z

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Jobs I’ve Done

Usherette in a cinema

Washer-upper

Waitress

Chef’s assistant

Data entry clerk

Bartender

Janitor in a school

Farm worker

Telesales person

Bouncer/doorwoman

Neuroscientist

Voice over artist

Scientific script writer

Tutor at a med school

Post your list!

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Well this is a sausage-fest

The Harvard newsletter has just published an article congratulating those faculty and alumni who have been admitted to the National Academy of Sciences. This is a huge achievement and possibly the highest US accolade for scientists. I have no doubt that each new member is highly deserving of admission, but there’s not a single woman among the new members. Is this a Harvard problem or a NAS problem?

http://harvardmagazine.com/2014/05/national-academy-of-sciences-adds-harvard-members-2014

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H-Mart open in Central Square!

H-Mart, the Korean grocery store, is open in Central Square and 7pm last night it was carnage in there!

I can see I’m going to have a love/hate relationship with this place. Love because it has all of the best aspects of an Asian supermarket and more. Hate because everyone else is going to love it and it’s always going to be busy!

The Central Square H-Mart has a mini food court at the front on the Mass Ave side of things. There is a Paris Baguette sandwich and patisserie place, a Go-Go Curry! and a Sapporo Ramen place that last night was sold out of ramen. Everyone loves ramen.

I couldn’t take an exhaustive tour of the store because it was so packed but I did get a bargain on some pork bulgogi ($2.99 a Ib) and bought a tray of accompaniments to the Bulgogi ($11.99) and some Asian snacks.

As I left (via one of the side exits to avoid the crush of disappointed ramen hunters at the front of the store) a young woman handed me a melamine dish painted with fruit and homely scenes saying “free gift”. She didn’t seem to have an H-Mart uniform on so maybe she was using me a mule for her shoplifting. Anyway, the joke’s on her as I now have a rather kitsch melamine tray holding my planting supplies. All in all a successful first trip except for the ramen.

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Do women take on too much lab work?

This week I had my Faculty ‘Annual’ Review. The main outcome was that I was falling behind in publications because I was spending too much time at the bench. This may sound paradoxical but it is pretty much guaranteed that the work that I’m doing at the bench right now; cloning a viral construct and packaging biomarker samples for my mentor (yeeeeah) are not likely to lead to a 2014 paper. Whereas I have a paper that is 80% written that just needs a few final experiments. However, I cannot get to that paper because this vector needs to cloned ASAP so that my mentor can present results to the funding agency in September.

The irony is that I didn’t need to be told that I was doing too much bench work. Many times I’ve gazed from the bench with envy at my mentor’s postdoc (who seems to only do experiments that generate direct data for papers) sitting at his desk leisurely putting together figures for a paper or catching up on the literature. Part of this is our different skill set. He has no molecular biology experience and only works with already established transgenic lines, so he doesn’t have to create resources. My projects are rather labor-intensive and amongst other things require the generation of new viral constructs and stereotaxic surgery to administer them.

The funny thing is, when I look around the surgery suite at others performing similar injections, the collection of murine surgeons is overwhelmingly female. On the whole, the men of our department seem to wangle it so that one or two (female) technicians perform the majority of their surgeries. This isn’t just limited to those of us on the lower rungs; I regularly see women with their own lab staff in the surgery suite, whereas the guys in this department seem to abandon bench work for good as soon as that first RO1 or even K award is granted.

Why is this? Are women control freaks? I will admit that yes, I can be. I was badly burnt during my PhD when I sent off a construct to generate a transgenic mouse to an outside company and they sent me back WT mice. The few weeks to figure out that no, the transgene was not present was nothing compared to the lag time waiting for the company to ‘generate’ and then actually generate the mice. So, I am now reluctant to send things out if they can be generated in house, unless they are in the hands of a trusted collaborator. Also, while here in Boston I had some difficulties with one tech who was not a native English speaker. Miscommunication, or having to type out simple but comprehensive instructions, often led me to think that it was just quicker to do it myself – something that I think most people have experienced for a whole host of reasons. Yet, the majority of the time I don’t have trouble trusting the people that I work with to complete the task successfully and most of the time I am more than happy to delegate. So, control freaks? Maybe some of us, under certain circumstances.

How about wangling our way out of bench work? (If we can convince our inner control freak!). Well, it is no secret that on the whole women can be crappy negotiators in the workplace when it comes to salary (www.forbes.com/sites/meghancasserly/2012/04/03/why-american-women-lose-negotiation-linked-in-career/ or www.nytimes.com/2014/03/25/your-money/moving-past-gender-barriers-to-negotiate-a-raise.html?_r=0) but we’re not that bad at negotiation aside from a concern about social backlash (www8.gsb.columbia.edu/newsroom/newsn/1823/role-of-gender-in-workplace-negotiations#.U1qPiVVdU1Y). Interestingly, the work cited in that last link (also here: psycnet.apa.org/journals/psp/98/2/256/ and here: www8.gsb.columbia.edu/programs-admissions/sites/programs-admissions/files/abstracts/Emily_Amanatullah_Dissertation.pdf), indicated that observers are more likely to form negative impressions of a self–advocating negotiator if the negotiator is female rather than male. So maybe women are on the whole more reluctant to negotiate themselves out of bench work for fear of forming a bad impression? 

For whatever reason, it is important to carve out time so that grants are written properly and papers published. I’ve since negotiated with my mentor to put another cloning experiment on the back burner until my semi-complete paper is submitted. This is a step forward but it really only came about because of the annual review and I realize that it was long overdue.

 

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Grantomania!

I have been constantly writing grants now for about a year. I’m pretty sick of it but I need to keep going until I’ve established a secure funding program that will give me more flexibility in my work. I’m in a department with no hard money so there is no alternative.

At times like this when motivation is low it can be helpful to take a step back and look at the process. This morning I enjoyed watching this video made by film-maker Tiffany Schlain about the creative process. Everything in it is applicable to the process of writing grants.

http://www.brainpickings.org/index.php/2014/02/19/tiffany-shlain-creative-process/

One stage of the process that I’ve come to realize is essential to me is stage 6: “just step away’. Even if I just leave the draft of an application alone for one day when I come back to it I see it through fresh eyes and realize which parts aren’t clear and how to edit out the parts that I now realize are crap.

Unfortunately, until recently I never factored this break time into my schedule for grant writing (a schedule that at its worst has consisted of “sh*t I’ve got to write this application in a weekend!”) and usually ended up giving it to a mentor to look over before I’d really looked it over myself. Of course, this leads to a drop in the quality of feedback as they’re picking up on all of the blatant issues that I would have seen myself if I’d allowed myself the break from the application.

I’m getting better at it now. Ideally, I give myself a few days away from an application but at the worst leaving a rough draft alone for a night is has worked out better than pushing further with it that night. If it’s not working, give yourself a break.

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Questioning

Asking questions is fundamental to being a scientist. This morning’s questions: “Why did you put empty ice cube trays in the fridge?”, “Why do the bananas smell of fish?”.

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