Fever and Autism

OK, I've got a bit of a soap-box feeling about this issue.... the autism and vaccination thing.  I've been so blessed to have very average children, with no hints of autism, Aspergers, or anything on the spectrum.  I do know lots of parents who are worried about vaccines playing a role in the onset of these disorders autism spectrum disorders or ASD.

I believe the link between vaccines and ASD has been thoroughly  laid to rest.  Still, many really cling to this as a reason to delay or even refuse vaccinations for their children. The issue I have is twofold: one, by your not vaccinating you're putting my child at risk for disease.  Two: by maintaining focus on the vaccine/ASD link the energy/intellect/resources of researchers investigating ASD is distracted, sidetracked, derailed, and unproductive.

Case in point, this paper coming form the May 5 issue of The Journal of Autism and Developmental Disorders "Is Maternal Influenza or Fever During Pregnancy Associated with Autism or Developmental Delays?  Results from the CHARGE (CHildhood Autism Risks from Genetics and Environment) Study."

This study looked at over 500 kids who have been placed on the ASD.  Over 50% of moms reported having a fever while pregnant. Synopsis by Medscape: "Fever during pregnancy is linked to a 2-fold increased risk for ASD or developmental delay (DD) in offspring, new research suggests. However, using medication to lower the fever may counter this effect.


'The inflammatory process may have a damaging effect on the developing fetus in some women," lead author Ousseny Zerbo, PhD, now a postdoctoral researcher with the Kaiser Permanente Northern California Division of Research in Oakland, said in an interview with Medscape Medical News. "These results call for more studies looking at inflammation during pregnancy and risk of autism,' he added."

Sleep your way to thin

OK, I wish this were really true.  But maybe not sleeping is making you fat?

A new study, published April 11 in Science Translational Medicine suggests that not getting enough shut-eye might be a contributing factor to weight gain, diabetes, and other metabolic disorders.  Big time.

The researchers took 24 healthy volunteers and subjected them to a grueling 21 days of very little sleep and total day/night disorientation.  For four weeks, the volunteers were only allowed to sleep 5.6 hours of every 24.  Lights were kept on "dim" and the day/night schedule was shifted to 28 hours.

How did the volunteers respond?  Insulin levels dropped in all subjects to a level seen in pre-diabetes. Volunteers also measured a reduced resting metabolic rate, down 8% from normal.  Meaning, fewer the sleepy volunteers needed fewer calories to maintain weight.  Insulin levels, blood sugar response, and basal metabolic rate returned to normal within a few days of the volunteers resuming a normal amount of sleep, within the normal 24 hour day/night cycle.

What's the take home?
Missing out on sleep can effect you. Big time.  Sure, these volunteers were only tortured for a few weeks, and quickly went back to normal.  But what if you're trying to survive on 5-6 hours of sleep a night for years?  Decades? This study suggests it can take a significant toll on your basal metabolic rate to the extent that if no other variables change would lead to 12+ lbs gained in one year. And missing out on the extra sleep can result in insulin insensitivity - a serious pre-diabetic state. There's lots of other animal and human studies supporting these conclusions.

Now, being realistic, and being a mom of two little girls who have their own definition of sleep that rarely takes into account Mom's need for shut-eye, I know how hard getting all your zzz's can be.  But this study might help give you a little more encouragement to try to catch a nap when you can, or maybe try to turn in when the kids to a couple times a week.  Your waistline and your longevity might benefit in the long run.


Oh, in case you're wondering about if the volunteers were compensated, "Participants received payment for volunteering in this study, equivalent to ~$10 per hour when in the laboratory."  They also got meals. No mention of them being provided video games.

The article:

Adverse Metabolic Consequences in Humans of Prolonged Sleep Restriction Combined with Circadian Disruption
Orfeu M. Buxton, Sean W. Cain, Shawn P. O’Connor, James H. Porter, Jeanne F. Duffy, Wei Wang, Charles A. Czeisler, Steven A. Shea 


The abstract found here. 

A private study

Found this story today. Wow.

OK, I wanted to post this on my "regular" blog, but thought it fit better here.  I mean, there's a phenomena out there that people acknowledge, deny, joke about, but it's never really been investigated.  Brave souls. I'd love to see the grant application for this one.

Quote from the article:

Having 3 distinct regions, the G-spot emerged with dimensions of length (L) of 8.1 mm x width (W) 3.6 mm to 1.5 mm x height (H) 0.4 mm. Upon removal of the entire structure with the adjacent margin tissues, the G-spot stretched from 8.1 to 33 mm.

Takeaway message: as much as we think we already know about anatomy, apparently there's still more to discover.  Well, maybe more to document. 

Bottoms up, little worms!

Caenorhabditis elegans Battling Starvation Stress: Low Levels of Ethanol Prolong Lifespan in L1 Larvae

So.... 
"Starving worm larvae that usually live 10 days could survive 20 to 30 in the presence of alcohol. "

Why I need to get back to this.

At the park today, another Mom and I were talking about the color of our children's hair.  I have two red-heads.  She has one red-head, one dark haired child. Here's the conversation:

Other Mom: Did you know red hair comes from one recessive gene carried by both parents?

Me: Yes, I believe it's the melanocortin receptor type 1 (MC1R)  gene.

OM: Well, I read that if both parents carry the gene, then they have a 40% chance of having a baby with red hair.

Me: Umm.... I'm pretty sure if it's a single gene trait, it would be expected 25% of the time.

OM: No, I read 40%.  Because it's recessive.

Yeah.  I let it go.  But guess there's more work to be done.

Please, the few of you who read this (and do not have Ph.D at the end of your name), tell me you know why it should be 25%.

I'm not lazy, I'm immunizing my kids.

I like to think I'm a loving and attentive mother. A clean one, not so much. So when some scrap of information comes in that makes me feel lauded for my laziness, I embrace it. Today's article comes through the graces of Uncle Jim, and the NEJM.  "Exposure to Environmental Microorganisms and Childhood Asthma".  I just love these medical titles. They really tell you what you need to know in as few words possible.

The punchline.
So, kids on farms as compared to kids not raised on farms (most of the kids I know) have less asthma, breathing problems, etc.  Why?  Well, I always thought it was because they were exposed to more things as kids, so their immune system got an extra workout.  This article supports this and gives some proof as to why.

What did they do?
Two big studies looked at how much bacteria farm kids as opposed to city kids were exposed to. Two separate methods were used, one used a fancy type of flypaper to trap bacteria, the other looked at mattress dust collected with a vacuum. Gotta love how low-tech can give high-quality data.  Mix the bacteria collected with standard culturing and staining techniques and fancy DNA sequencing and showed the farm kids were exposed to not only a greater number, but a greater variety of bacteria and fungus than the city kids. And those farm kids, in all their wholesomeness, had fewer cases of asthma and atopy than the non farm-kids.

Why is this important?
Well, it's been known for some time that kids on farms, or kids exposed to lots of dander, bugs, dirt, etc, actually do better in terms of autoimmune issues (asthma, atopy, and the like) than kids kept in a cleaner environment.  While this study was not absolutely connect the dots to bacteria/fungi exposure and bolstered immune system, it brought us closer.  So, maybe it's not so bad when, at Grammy's house, my 1 year old rubs her piece of bread on the floor where the dog's fur lays in small tufts, and I, much to my parents' chagrin, let her take a bite.  Maybe it's OK to let her eat a little bit of dirt.  OK, a lot of dirt.  Maybe exposing her to lots of little bugs at an early age is gonna help her not have to buy lots of Benadryl, Allegra, and whatever other miracle antihistamine is made in the future.  And maybe I can stop feeling a smidgen of Mommy Guilt over letting her be a kid. Maybe she knows something I don't.

Just another pretty face

Today's paper is really neat. The group made a mouse mutant that had a craniofacial defect (read: messed-up looking face) and traced it to a molecular/genetic pathway.  And all in 4 jam-packed figures and tons of experiments.  I've got a soft spot in my heart for the craniofacial researchers, so this paper jumped out at me.

The title is a mouthful: The E3 ubiquitin ligase Wwp2 regulates craniofacial development through mono-ubiquitylation of Goosecoid. The 30 second summary: mice lacking the gene Wwp2 have odd faces and jawsf.  Wwp2 gene makes a protein that modifies, and activates another protein, Gsc (Goosecoid) which binds to and activates yet another gene, Sox6, which is a key regulator of normal head and face development.


The Data:
Using a gene trap method of deleting genes in mice, the Wwp2 gene was deleted.  The knock-out mice were born, but had defects in their jaws and face: they had stubby noses and domed heads.  The way they made the mice they could trace where the Wwp2 gene should be expressed by using a blue dye. They traced where the normal expression of Wwp2 was using the dye. They used a gene already known to be involved in craniofacial development, Sox9 as a control, and showed Wwp2 was necessary for normal development.  They looked further into Sox9 and found that when it is overexpressed, Wwp2 expression increases too.  Could they be linked?  They did direct DNA binding assays to show Sox9 does, indeed, bind to and controls the Wwp2 gene.

Great.  Moving on, the Wwp2 gene makes a protein called a ubiquitin ligase.   Wwp2 protein then acts on other proteins to decorate them with these teeny itty bitty modifications called ubiquitin.  Often, this targets the protein for destruction in the proteosome, but not always.  If a long chain of ubiquitin is added, the protein is destroyed; if only one little ubiquitin is added onto the target protein it can change the protein's behavior: increase or decrease it's activity, change where it likes to hang out in the cell, etc.  The first question is what protein does Wwp2 modify.  Second question is what does that modification mean for a cell, particularly one that is trying to become a jaw or nose.

They had a few hints as to the first question.  Based on the protein sequence recognized by Wwp2, they came up with four candidates and quickly showed by direct protein-protein binding assays and ubiquitination detecting assays that Wwp2, indeed, added ubiquitin to the Goosecoid protein (Gsc).  The second question, what does Gsc getting a ubiquitin from Wwp2 do to a cell, took a bit more work.  They looked at if Gsc got sent to the trash can after Wwp2 ubiquitinated it. Nope, Gsc levels stayed the same. It so happens that Gsc is a transcription factor: a protein that acts at the DNA level to change expression of other genes.  They looked at how many ubiquitin molecules Wwp2 added to Gsc, and only one was added, suggesting the ubiquitination of Gsc by Wwp2 changes Gsc's activity on genes at the DNA level.  So begins what probably was a stab in the dark that got lucky.  They did gene expression analysis to determine if the expression of any genes potentially involved with craniofacial development changed when Gsc was modified by ubiquitination.

And in comes Sox6.  Sound familiar?  Well, sort of.  In the same family as Sox9, Sox6 is yet another transcription factor that is involved in cartilage biology... just the sort of thing that could direct normal growth of bone, and also just what, when disrupted, could lead to abnormalities.

The result:
OK, so I skipped some of the experiments.  But really, they were very thorough.  And this post is already getting long. A cool little model from this paper is that the first gene they looked at, Wwp2, is turned on by Sox9, goes on to influence another protein, Gsc, which act on another gene, Sox6 to guide normal head and face development in mice.  Talk about a cascade effect.

There's always more work to be done.  I'd like to see the phenotype of the craniofacial defects be echoed in a Sox6 mutant. This would shed more light if this is the only body region affected by this particular signal cascade.  I've no doubt there's lots of literature on Sox9, but I'd like to see what the instigating signal to the little cells are that kicks off this whole signal sequence.  I mean, not every cell ends up being a part of your nose or cheek, so what sets these cells off on this fate.  And then, linking to humans, are defects in this pathway seen in humans bearing craniofacial anomalies?  And don't you love saying cranifacial anomaly?  I do.

See you next week!