Why high-fat, low-carb diets help some epileptics

March 19, 2015 § Leave a comment

A series of pie charts depicting the calorific contributions from carbohydrate, protein and fat in four diets: the typical American diet; the Atkins diet during the induction phase; the classic ketogenic diet in a 4:1 ratio of fat to combined protein and carbohydrate (by weight); and the MCT oil ketogenic diet. Image from http://commons.wikimedia.org/wiki/File:Ketogenic_diets_pie_MCT.svg

A series of pie charts depicting the calorific contributions from carbohydrate, protein and fat in four diets: the typical American diet; the Atkins diet during the induction phase; the classic ketogenic diet in a 4:1 ratio of fat to combined protein and carbohydrate (by weight); and the MCT oil ketogenic diet. Image from http://commons.wikimedia.org/wiki/File:Ketogenic_diets_pie_MCT.svg

Antiepileptic drugs don’t work for one-third of patients. Instead, those patients usually eat ketogenic diets, high in fat and low in carbohydrates, which somehow stops seizures. In a paper just out in Science, researchers report how ketogenic diets work at the molecular level and say they designed a new drug that mimics the molecular effects of ketogenic diets.

“Current antiepileptic drugs are designed to target molecules that regulate electrical currents in neurons,” says Tsuyoshi Inoue at Okayama University in Japan, who led the work.  He adds that they “focused on antiepileptic actions of ketogenic diets” so they could find other ways to target epilepsy, particularly through metabolism.

Ketogenic diets force the body to rely on ketone bodies instead of glucose as an energy source. Inoue and colleagues explored what happens in single neurons in mouse brain slices when their energy source is switched from glucose to ketone bodies.

“We found that a metabolic pathway, known as astrocyte-neuron lactate shuttle, regulates electrical activities in neurons,” says Inoue.

An enzyme in the pathway is lactate dehydrogenase. When the energy source went from glucose to ketone bodies, the investigators realized that the switch in energy source inhibited the pathway via lactate dehydrogenase and caused the neurons to become hyperpolarized.

When the investigators inhibited lactate dehydrogenase in a mouse model of epilepsy, the animals suffered fewer seizures.

Next, the investigators used an enzymatic assay to see which existing antiepileptic drugs act on lactate dehydrogenase. They found a drug called stiripentol, used to treat a form of epilepsy called Dravet syndrome, inhibits lactate dehydrogenase. The investigators modified the drug’s chemical structure and found an analog that better suppresses seizures than the original.

Inoue says that inhibitors of lactate dehydrogenase can be “a new group of antiepileptic drugs to mimic ketogenic diets.”

Blog takes a break

August 13, 2013 § Leave a comment

Wild Types is taking a summer break! Check back at the end of the month for new posts.

Jon Lorsch to head National Institute of General Medical Sciences

March 25, 2013 § 1 Comment

Jon Lorsch, a professor at Johns Hopkins University, will be the next director of the National Institute of General Medical Sciences. He’ll arrive at the institute in Bethesda, Md., this summer.

Lorsch, an active member of the American Society for Biochemistry and Molecular Biology’s mentoring committee, will oversee a $2.4 billion budget that supports primarily fundamental research and scientific workforce training.

“With his reputation of being a broad-minded and visionary thinker with strong management skills, I am confident that Jon will lead NIH’s basic science flagship to keep the U.S. at the forefront of biomedical research,” Francis S. Collins, director of the National Institutes of Health, said in a statement announcing the appointment on March 25.

Lorsch will take the NIGMS reins from Judith H. Greenberg. Greenberg has served as the acting director of the institute since July 2011, when Jeremy Berg stepped down, after holding the director position for eight years, to become the University of Pittsburgh’s associate senior vice-chancellor of science strategy and planning.

Berg, who now is also president of the ASBMB, said he was pleased with the appointment: “Jon is a great choice. He is an outstanding scientist with ideas spanning many disciplines and with great teaching and training experience. He also led the curriculum reform efforts at Johns Hopkins and balanced clinical and basic perspectives very well.”

Berg continued: “He is very personable and is a good listener but is not at all afraid of tough issues. Jon is one of a small group of people whom I frequently reached out to when I was NIGMS director for his perspectives and advice.  NIGMS will be in good hands.”

Lorsch holds a Ph.D. in biochemistry from Harvard University and completed a postdoctoral stint at Stanford University. His group at Hopkins developed a fully reconstituted yeast translation initiation system, which the group used to understand the molecular mechanisms of the process by which the genetic blueprint in cells gets turned into working protein machines.

According to a Hopkins bio, Lorsch is thought to be the black sheep in his family “because, out of five males, he is the only one without a degree from Harvard Business School.”

ASBMB survey of young scientists sparks Twitter conversation about gender disparities

January 24, 2013 § Leave a comment

  1. Interesting note from bit.ly/UncG27 – Men outnumber women as applicants for faculty positions in biochem by almost 3:1. #WiS #STEM
  2. Survey suggests due in part to lack of knowledge of family-friendly policies… RT @Ilovepigenetics: @(me) Why are women leaving before TT?
  3. *********************************************************************************************************************
  4. @Ilovepigenetics @biochembelle Had a boss who’d let the women do the work, then take the credit, women never fought back ….
  5. @AjazSadia @Ilovepigenetics @biochembelle used to say if you were any good, you’d be raising family than working in the lab. So.
  6. @biochembelle That is the biggest sign about how TT is something I know has no interest to me based on how it’s set up. Despite the science
  7. *********************************************************************************************************************
  8. @biochembelle A TT job demands that your career comes first-TT women don’t have ‘wives’ at home making dinner. Whose career comes first?
  9. @dave_bridges @biochembelle I have seen many career focused women choose to follow their husband’s career. It’s more than dinner, housework.
  10. @Ilovepigenetics @dave_bridges Yep. Many surveys that say women still shoulder larger share of domestic duties in dual-career households.
  11. *********************************************************************************************************************
  12. .@biochembelle @Wikisteff We’ve got a majority of F in our biochem major here at AU. Fac used to be 1:1 M:F. After recent turnover is 4:2
  13. @biochembelle @dave_bridges Big disparity in # of female faculty. UofM A2 has many in powerful positions; other institutes not so much.
  14. @Wikisteff At our institution, Chemistry is 53% male over last three years. Institution is 43% male over same time. @biochembelle
  15. Though, I think there remain disparities in attitudes/pressures vs. official institutional policies. @biochembelle @Ilovepigenetics

Happy Holidays!

December 21, 2012 § Leave a comment

Image created by ASBMB's designer extraordinaire, Marnay Harris (http://marnayharris.com/)

Image created by ASBMB’s designer extraordinaire, Marnay Harris (http://marnayharris.com/)

The 12 days of Labmas

December 13, 2012 § 1 Comment

  1. SciTriGrrl
    @AmasianV @DrLabRatOry @biochembelle on a rhyming note: milkin’ = sulkin’? How many 9 postdocs sulkin’ ?@dr_leigh
  2. SciTriGrrl
    @biochembelle @DrLabRatOry @AmasianV the 5th day has to be ” five dead rats”! See how well that fits?#12daysoflabmas
  3. DrLabRatOry
    On the 3rd day of labmas my PI gave to me: 3 bench friends, 2 thermal gloves, and an old book of crystallography @AmasianV @biochembelle
  4. biochembelle
    On the 2nd day of labmas, my PI gave to me… 2 thermal gloves [both lefties] (and an old book of crystallography). @DrLabRatOry @AmasianV
  5. AmasianV
    @biochembelle on the first day of labmas my PI gave to me…

Urinary metabolic profile of clinical depression

November 19, 2012 § Leave a comment

Image courtesy of Kevin Dooley http://www.flickr.com/photos/pagedooley/2811155478/

Clinical depression, also known as major depressive disorder, robs its victims of interest and pleasure, sleep, appetite and concentration. Clinically depressed people also suffer from excessive fatigue and dark thoughts.  The illness is a major cause of disability, suicide and physical problems. However, a diagnosis for the illness is based on psychiatric reviews, which can be subjective. In a paper in Molecular & Cellular Proteomics, Chinese researchers described a test that could objectively diagnose the illness.

Depression is a complex mental disorder that involves multiple factors. The disease diagnosis is subjective because it can present a number of different symptoms and the exact causes for it are not understood. “Despite overwhelming efforts to identify the biomarkers for MDD, there were still no empirical laboratory tests available to diagnose MDD,” says Peng Xie of Chongqing Medical University who was the senior author on the MCP paper, adding that the current subjective diagnosis process has a considerable error rate.

The researchers decided to analyze urine, a sample that can be collected easily, for metabolites that could act as markers for depression. By using nuclear magnetic resonance spectroscopy, they were able to identify five molecules in urine that together seemed to sort out people who suffered from depression from those who didn’t.

The molecules were malonate, formate, N-methylnicotinamide, m-hydroxyphenylacetate and alanine. Malonate and formate are primarily involved in energy metabolism, m-hydroxyphenylacetate has a role in gut microbial metabolism and N-methylnicotinamide N-methylnicotinamide affects tryptophan-nicotinic acid metabolism. Alanine is one of the 20 amino acids used to make proteins. Xie says, “Based on the previous clinical and basic studies, we suggest that disturbances of these metabolic pathyways are implicated in the development of MDD.”

Xie says the researchers zoomed in on a few metabolites as markers because, in clinical practice, it is not convenient or economically feasible to simultaneously measure a large number of metabolites for diagnosis. The current work is a proof-of-concept and opens up more avenues of investigation. Xie says for one, the researchers would like to collect urine samples from depression patients and healthy controls from more ethnically diverse populations to further validate the diagnostic performance of the five metabolites. They also would like to dig deeper in to the underlying metabolic pathways of these five molecules to see if they can uncover how these biochemical pathways play into the disease.

What happens in study sections, stays in study sections.

November 12, 2012 § Leave a comment

  1. drugmonkeyblog
    The preliminary results show that she has no trouble recruiting a diverse subject pool. #studysectionafterdark
  2. StrangeSource
    She pushed me away. “What’s wrong now?” I pleaded. “Let’s talk budget.” #studysectionafterdark
  3. mbeisen
    Her eyes were brown. The sheets were pink. #studysectionafterdark
  4. mbeisen
    “You’re above MY payline.” #studysectionafterdark
  5. mbeisen
    “I bet your IRB wouldn’t approve THIS” #studysectionafterdark
  6. mbeisen
    It was going so well until she suggested we do something novel. #studysectionafterdark
  7. drugmonkeyblog
    #alwaysthemoodkiller RT @mbeisen: It was going so well until she suggested we do something novel. #studysectionafterdark
  8. StrangeSource
    I…I just don’t think this is feasible, I stammered. @mbeisen @drugmonkeyblog #studysectionafterdark
  9. mbeisen
    I asked for her number. She said “1 for innovation. 5 for approach.” #studysectionafterdark @boehninglab @drugmonkeyblog
  10. drugmonkeyblog
    …her voice had a sultry rasp….from handling five primary reviews that day… #studysectionafterdark @boehninglab @mbeisen

Cellular organelles get into the election year

October 19, 2012 § 1 Comment

  1. mr_graba
    Students now creating memes to do mudslinging against other organelles. Real scientists joining the fun! #authenticlearning #education
  2. mr_graba
    RT @NuCleanNucleus: #funfact Did you know there’s a foundation devoted to mitochondria’s screwups? I think theres some ice for that burn #iceicebaby
  3. mr_graba
    RT @NuCleanNucleus: @Reticulum_Rocks , when u screw up, you send the person TO the ER! #lol #badsciencejoke
  4. PlasmaMembrane4
    @mr_graba will obviously vote for us, because we are like border control. The harmful things are kicked out, and the good things are let in!
  5. mr_graba
    RT @Reticulum_Rocks: Besties! We work together with the Golgi Body and share chemical products! @wholly4golgi
  6. mr_graba
    RT @Wholly4Golgi: We package your macromolecules up better than FedEx.
  7. mr_graba
    RT @Peroxisomes2012: @PlasmaMembrane4 @Golgi_Body2012 Viruses get inside cells via proteins in plasma membranes
  8. mr_graba
    RT @Lysosomes2012: casually digesting some bad organelles
    #lysosomelife #cellprobs
  9. mr_graba
    RT @Peroxisomes2012: @TheNucleus2012 Red blood cells don’t have nuclei
  10. mr_graba
    RT @TheNucleus2012: Why vote for chloroplast? It is something that is only found in plants. Vote for an organelle found in you, me, and your Dog! Vote Nucleus!
  11. mr_graba
    RT @Golgi_Body2012: If you want a healthy nervous system, don’t vote for peroxisomes. #Golgi2012
  12. mr_graba
    My students are running election campaigns for cell organelles. Creativity explosion in the classroom!

The 2012 Nobel Prize in Chemistry on Twitter

October 10, 2012 § Leave a comment

[View the story “The 2012 Nobel Prize in Chemistry on Twitter” on Storify]

The 2012 Nobel Prize in Chemistry on Twitter

Any time biochemists win the Nobel Prize in Chemistry, chemists start asking questions what exactly it means to be a chemist. Here’s how this year’s Nobel Prize in Chemistry to Robert Lefkowitz and Brian Kobilka for G-protein-coupled receptors played out on some Twitter handles.

Storified by Raj Mukhopadhyay · Wed, Oct 10 2012 10:42:07

Nobel: A Quaint Anachronism? Critics find the Nobel committee’s selection rules & categories out of date with science.

Happy to see Biochemists winning in . Need to gray the lines between disciplines to make largest impacts.

But, again, is that saying something about our field, in general? Do we need a jumpstart? Better PR? Better translation?

It’s a collective action problem between “us” and the Nobel Medicine folks. You get 3 bullets max to fire, once a year.

Who’s going to share their pie w/the biologists? Apparently, it’s the chemists.

– Problem for me is the reverse: Why don’t more chemists win for Med, Physics, Lasker, etc? (2/2)

2C) Are we just getting our collective panties in a bunch over this?

‘No’ RT : Question: if we asked Lefkowitz/Kobilka “are you chemists?” What do you think their answer would be?

Probably “No, thank God, otherwise we wouldn’t have won the Nobel Prize”?

And as arguments begin over whether biochemists are chemists, check out my 2009 story on the chem

I want South Park characters arguing over fairness of Nobel chem prize being awarded for biochem. Someone make this happen.

The 2012 Nobel In Chemistry. Yes, Chemistry.: A deserved Nobel? Absolutely. But the grousing has already started…

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