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It’s time for the bacterial evolution crowd to get their own toys

Oct 04 2010

ResearchBlogging.org
Molecular phylogenetics has revolutionized our understanding of biodiversity and evolution like no tool before it. The advent of using the divergence among the gene and protein sequences of different organisms as both a proxy for the biological species concept (at the species level) and a way to compare organisms with no obvious shared morphological or cellular features has resulted in the most sweeping change of how we classify the diversity of life since Linnaeus. Like any paradigm shift, however, the new data available opened up a Pandora’s Box of new issues that needed to be grappled with.

One of the major discoveries that came to light was that prokaryotic organisms (often called “bacteria”, but actually made up of two very distinct lineages, the Eubacteria and Archaea) are not quite what we thought they were. You see, Darwinism laid the foundation for how evolutionary biologists interpret the world, and while Darwin got a lot of things right, there were many things he had no idea even existed, that have shaped how we understand evolution today (as there will be many things we don’t know about today that will shape how scientists in 150 years understand evolution). While Darwin’s concepts for descent with modification fit the multicellular world pretty damn well, things get a little muddled in the unicellular world, especially when we leave the eukaryotic cells many of us know, and move to the bacteria.

Bacteria don’t play by the rules that work so well for the multicellular among us, and the differences are at the heart of a scientific debate that has been playing out for two decades. In the early stages of molecular phylogenetics, it was thought that the history of life’s evolution could be revealed if we compared the sequence of a ubiquitous gene across all taxa. The small subunit (SSU) of the ribosomal RNA was chosen as the appropriate gene because no life form lacks ribosomes, and because of it’s important role, the DNA sequence that codes for the functional RNA is highly conserved. As a result, the SSU is the most diversely sequenced gene around and is used today as the gold standard for comparison of bacterial and some eukaryotic species.

But there was a surprise in store when people started to sequence other genes from diverse bacterial lineages. The phylogenetic trees resulting from these new data did not match those of the SSU. In some cases, the differences were dramatic. It had been clear for some time that bacteria could exchange DNA, but the extent and potential evolutionary distance of the exchange took the community by surprise. Indeed, there are some bacterial genomes that appear to be a mixed bag of genes from diverse sources, such that their closest sister taxon can not be identified with certainty (e.g. Zhaxybayeva et al 2009). The evolutionary picture within and among bacterial groups is so confounded by lateral gene transfer (LGT), that the term “Tree of Life” has been abandoned by many, in preference of some variation on “Web of Life”.

On top of the issues with LGT, there is the problem that bacteria just don’t speciate the way eukaryotes do. The most recent issue of Biology & Philosophy (2010, 25(4)) is dedicated to the discussion of bacterial evolution and how it differs from that of eukaryotes, but the paper by Lawrence and Retchless (2010) really drives to the heart of the problem: we can not use models fashioned after evolutionary patterns in eukaryotes to understand prokaryotic evolution because the speciate in fundamentally different ways.

This message has been repeated far and wide and several researchers are actively proposing novel models for use in prokaryotic systems (e.g. Bapteste et al. 2009). Despite this, paper after paper are churned out using traditional phylogenetic methods to try and classify bacteria using the same assumptions applied to eukaryotic systems. What the hell is going on?

To tell you the truth, I don’t know. I think part of the issue is availability and acceptability. Tried and true phylogenetic methods are well known and reasonably well understood by a large community of people. If one is writing a paper or grant proposal, introducing controversial or novel methodology is one way to make the process exceedingly more difficult on yourself (a whole new thing for reviewer 3 to reject outright without understanding it!). Playing it safe means that you can cite the large body of literature that is also applying the same methods, in some sort of schooling fish mentality. Another factor might be the radicalization of the LGT movement by researchers not willing to abandon the Tree of Life idea, for personal or political reasons. Rarely have I seen such vitriol unleashed at conferences as when the topic of rampant prokaryotic LGT comes up.

But the data are the data. It is abundantly clear that bacteria violate the assumptions inherent in the methodology currently used to model evolutionary history (even worse than eukaryotes do, but that’s a different story). Until the bacterial evolution community comes up with and embraces new methods to model prokaryotic evolution, leaps in our understanding of that process will be limited.

References
Zhaxybayeva O, Swithers KS, Lapierre P, Fournier GP, Bickhart DM, DeBoy RT, Nelson KE, Nesbø CL, Doolittle WF, Gogarten JP, & Noll KM (2009). On the chimeric nature, thermophilic origin, and phylogenetic placement of the Thermotogales. Proceedings of the National Academy of Sciences of the United States of America, 106 (14), 5865-70 PMID: 19307556

Lawrence, J., & Retchless, A. (2010). The myth of bacterial species and speciation Biology & Philosophy, 25 (4), 569-588 DOI: 10.1007/s10539-010-9215-5

Bapteste, E., O’Malley, M., Beiko, R., Ereshefsky, M., Gogarten, J., Franklin-Hall, L., Lapointe, F., Dupré, J., Dagan, T., Boucher, Y., & Martin, W. (2009). Prokaryotic evolution and the tree of life are two different things Biology Direct, 4 (1) DOI: 10.1186/1745-6150-4-34

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What I am listening to while I read your proposal

Oct 02 2010

“The cost is more than what you get paid, but do it anyway….”

Word.

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Job vacancy: Journal Club Killa

Oct 01 2010

Having filled our previously advertised job in Seminar Napping, Employment University has a new position available immediately, entitled, Journal Club Killa.

Requirements:

Applicants must religiously attend journal clubs on topics they know little about, but purport to do research in. They must be able to ask a bevy of questions that derail the discussion into obscure topics of self-interest and be persistent enough to smother constructive conversation. The successful applicant will also never print out the paper being discussed and repeatedly spout random inquiries that make plain the fact that they never read the paper to begin with.

Preferred Skillz:

Candidates who prefer to talk at length about the way research was done 20 years ago are strongly encouraged to apply, particularly if they try to pass it off as though they are doing “cutting edge” work. Using the same arguments week after week, regardless of the paper of choice will also be reviewed favorably.

Compensation:

The job pays only in self-satisfaction and ill-tempered glares from presenting students, but if you are interested in this position, this seems to be all the compensation you ever seek.

Applicants should send three letters of reference attesting to their ability to read from the paper of the student next to them and inability to use anything but their outside voice when asking said student questions while others are talking. If possible, letter writers will be asked to comment on the candidate’s refusal to back down from any position on how new data are wrong, despite overwhelming contrary evidence.

Please forward application packets to:PLS, Department of Science, Employment University

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Panelized

Oct 01 2010

On top of several other things I have going on these days, I’m also reviewing a stack of grants for an NSF panel. I have done a good amount of ad hoc reviews for NSF and other funding agencies before, so I didn’t think this would be all that much different. Oh, but it is.

To start with, some of these proposals are pretty far outside of my expertise. When you get an ad hoc review it often (though not always) falls within your close field, which is why they sent it to you. When you have been assigned 12 reviews out of ~100, the odds are against even half of those being related to your work.

Another issue is the sheer volume. Proposals are dense and it takes a bit to get through on, summarize your thoughts on their system and approach and comment intelligently on the whole thing. Doing that 4 or 5 times takes a lot of time. 12 times for grants that are mostly outside of work? That’s a whole new ball game. I would be lying if I didn’t tell you that I am about 3/4 through and feeling like my brain has turned to oatmeal. Remember that I am also teaching, dealing with everything going on in my lab and trying to write a new grant for the Oct NIH deadline.

Finally, the feedback is giving me a bit of stage fright. When you do ad hoc reviews you submit them and go about your daily business. When you are a panelist, you instantly have access to all of the other reviews on the proposals you are reviewing, as soon as yours is submitted. As soon as the submit button is hit, you can see how your impression measures up against all the other reviewers, and I admit that has made me a little more vigilant in making sure I can back everything I say up with data. It’s not that I did crappy reviews in the past, but the instant comparison between my opinion and that of Big Name X is slightly intimidating as I hit the submit button. In some cases I am right in line with others and in some cases I have a very different opinion of the proposal. In the latter cases, it means that I need to do more reading to make sure I can defend my position when it comes to the panel, which BTW, is yet another unknown for me.

I am glad I am doing this and looking forward to the experience, but the process has been more draining than I thought it would be and finding time to get to all of them has really cut into the time I spend with my family. I’ll be happy when it is over.

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The interesting genomes are almost gone!

Sep 29 2010

So I was minding my own bloggy business the other day and ran across a link at the John Hawks weblog to the discussion we were having the other day about press announcements pre-empting publishing. While reading, I came across this gem:

I think genomics has come to an inflection point — organisms whose genomes are obviously of some utility, but which have not yet been subject of a whole-genome sequencing project, are getting scarce. It’s not enough to sequence a genome, if you want to do glamor science. You have to have some, you know, science in there — pushing theoretical understanding in some way.

I was going to leave a comment there, but it’s one of those comment-free monoblogues, so we can discuss this here instead. Whereas I agree with the second part about needing to find something interesting in a genome and do a thorough analysis to get it into a glamor journal, the first part is what made me stop and say “WUT?” This is the kind of stuff that drives me nuts, as I have mentioned before because what is really meant is that we’re running out of ‘interesting’ animal genomes to sequence. If you ask me, we hit that point a while back, but there are a shit-ton of interesting genomes out there we have virtually no idea about.

Depending on who you believe*, there are probably 5-7 ‘supergroups’ into which all eukaryotes can be classified. Of those groups, 2 (or 3, again, based on classification scheme) have not a single published genome sequence and many major lineages within those groups are also unrepresented. We have few or no genomes to use when investigating some of the major innovations in eukaryotic evolution. We know virtually nothing about ecologically important (and truly bizarre) organisms, like dinoflagellates, at the genomic level. To say that interesting genomes are getting scarce is to admit that your view is “if it ain’t animal, it’s crap”, which is a pretty sad statement for a biologist.

I’m not suggesting that we all go out and find a bizarre beast to work on, but simply that we allow for the possibility that there is important science happening outside of animals (and even plants, on a bad day). There is even the chance (though not a requirement) that the discoveries in Other organisms could advance the science in animals. You never know what unusual cell might change the way we look at fundamental cellular processes.

BERJAYA
Hey there, I’m Tetrahymena. We probably haven’t met, but there have been dozens of critical discoveries made using me as a study subject, including Nobel Prize winning research catalytic RNA and telomerase. But, you know, whatever. Oh, did I mention I have two nuclei that are different forms of essentially the same information, but function completely differently? Other than all that, I’m boring as hell.

*The fact that there is active debate on the major groups of eukaryotic organisms should be half decent evidence that we need to more broadly sample organisms rather than sequencing 1000 of the same genus.

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Why don’t you just pay them more?

Sep 28 2010

Everybody thinks they are underpaid. It’s true, and this sentiment probably even scales with the more money someone makes. We see it on public display in sports all the time and I’m sure it happens in the business world just as much. Most people that do a specialized job feel like they have outplayed their contract.

In the academic science game, this is certainly true. No one feels like they get paid enough, especially after years of training. Grad students don’t have a lot of take home salary, and while each level above them is an upgrade in pay, academics is not a place to get rich. There’s been a discussion at DrugMonkey about grad student pay and relative comparisons, but that’s not what I want to talk about today.

I’m more interested in why scientific trainees are not paid more*. Many people seem to think it is just a matter of the PI of a lab either not caring or being stingy. While undoubtedly there are plenty of uncaring and stingy people running labs, there are constraints on people who are neither, as well. This particular post was partly spurred by a comment by LabSpaces overlord Brian Krueger on one of Gerty-Z’s posts, in which he stated:

I think a lot of professors are stindgy bastards. It always really pissed me off when I was in a lab where the PI would brag about how much money he had to waste on new computers or whatever at the end of the fiscal year and yet the undergrads in the lab are unpaid and the techs haven’t seen raises in years. I say pay your good students and pay them well. Good people are really hard to find and the “compensation” of training is such a ridiculously arcane idea. Sometimes people need to eat too. And in this case, I think you’re right. A student shouldn’t have to choose between debt and research, especially if the PI can afford to pay them.

Now, to be fair, in response to my comment that I will elaborate on here, Brian did clarify that he was talking about a lab in which the PI genuinely did seem like a douche. But I do think this sentiment is held by a lot of students and postdocs, as evidenced from a couple of years reading this here blogosphere.

So what are the constraints on pay?

Well, the most obvious is grant funds. I realize that the typical trainee or technician doesn’t care where their money comes from, but the reality of their PI’s situation is relevant to the question. If we think about a postdoc, for example, the salary is only one part of the equation. If a PDF makes $45K / year, their benefits are roughly 60% of that, or $27K. Together, that’s $72K / year from a budget of a grant, but it gets better because in the submitted budget the PI has to factor in the university overhead. Now you’re looking at $72K X 55% (or so), which means that the hit to the grant budget is a little more than $110K / year. I know that I am in the minority of science bloggers in that I am primarily NSF-based in my finding opportunities, but I think people might be interested to take a look at the NSF funding info page and to get a feel for the median annual size of grants by NSF organization. If you don’t want to click on the link, I’ll spoil the surprise and tell you its in the $110K-$120K range. For BIO, it was $143K in 2009, but drilling down a bit you will see that even that number is slightly misleading due to some bigger money programs in the mix. If you look at DM’s post from yesterday on NIGMS at NIH, the median funding level would appear to be $220K per year there. You can see where this is going….

Students, despite popular belief, are no bargain on a grant either. Some departments subsidize them in a significant way, but if not, you’re talking a $25K salary, plus benefits (in the summer), plus tuition (no overhead paid on tuition, at least) and O/H on roughly $30K. All in all, about $60K / year. If you are writing an NSF budget and want to include a student, postdoc and actually do some work, publish it and talk about it at meetings, things get interesting.

So why can’t a postdoc get $5K more? Because $5K in salary is not $5K on a grant, it’s (($5K X 1.6) X 1.55) = $12,400 X 3 year = $37,200. I don’t know about everyone else, but I struggle to keep my budget within what has been suggested to me as a fundable range. Adding almost $40K is not an easy thing to do because we are in competition with similar proposals that may require less funds. If your labs runs on multi-R01 NIH fuel, a $5K raise for three postdocs for only three years means someone gets one year less to work in the lab. If you draw the short straw, would you rather have two years with an extra $5K in your pocket each year, or that extra year at $40K?

Another issue is unions. Whereas unions may be to the advantage of the whole, IME they can be smothering to a talented technician who deserves a solid raise. In many cases a substantial pay increase $5K-$10K can only be accomplished with a new job description that needs to be opened up for applicants and can be taken without question by a more senior individual from that union who possess the same title elsewhere. How many technicians or PIs are willing to risk that?

Graduate student unions also put restrictions on how much students can get paid. Although they ensure that students have a minimum salary, get raises and have a collective voice, they don’t allow for much flexibility in what can be paid to a student. Make no mistake, I think removing grad student unions would result in a worse situation for grad students, on the whole, but if you are going to complain about pay, your union is the place you should start.

And we haven’t even gotten to the issue of competitiveness. I would bet that most people reviewing grants would tell you that they don’t take into consideration what the proposal budget is, but I bet they are not telling you the whole truth. If the budget seems reasonable, no one pays attention. But, what if one investigator budgets $5K more per year in a three year proposal for a student, tech and PDF than someone else proposing something not to far off. The first proposal is going to come in $100K (15-20% of many NSF budgets for that amount of time) more than the other, and in less the science in the first one is substantially better for one reason or another, that is going to be noticed.

Finally, having grant funds and having money for salary can be two different things. While start-up funds are not categorized, grant funds are. Money in the computer budget, for example, is gold because you need to justify money in that category with a special form that needs to get cleared at you agency. Money earmarked for foreign travel and equipment is similarly guarded. A budget can therefore roll over a substantial amount of money from one year to the next without actually having any dollars available for salary.

I am writing about this because I had no idea how research budgets really work when I was a trainee and of course I could have used more cash in my beer fund pocket, but from the other side of the desk, it isn’t always that easy. Unless the overall budgets for proposals is allowed to make a jump (and at 10% funding rates, where is that extra coming from?), I’m not sure where the extra money is going to come from to give grant-supported trainees a substantial raise.

*I’m interested in my professors aren’t paid more too, but that’s a topic for another day

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Women’s health writeup

Sep 27 2010

Today we have a special series of posts on women’s health and the absurdity of claims in mainstream media. There will be a special stream dedicated to this today on the front page and Sci at Neurotic Physiology has a round-up post where you can read about the origin of this series and also find the different blogs that are contributing today. Go check it out.

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When did announcing science become the same as publishing science?

Sep 24 2010

When I was a postdoc, I used to make a Friday morning ritual of browsing through the latest issue of Science while drinking my coffee and listening to one of my favorite music podcasts. It was one of the highlights of my week, but that ritual has been long since buried by the simple fact that I just don’t have time during the day to casually read through a whole journal.

But this morning, I tried. I didn’t get all that far, however, because one item in the News of the Week section caught my attention and sent me looking around at other sources as well. Maybe I have just been oblivious to the subject of the article because it is not my game, but I nevertheless found the piece on Stephan Schuster getting “scooped” in his efforts to sequence the genomes of both the cacao tree and the Tasmanian devil. Why this article was so interesting is all in the nature of the scooping.

When I think of getting scooped, it means that another lab has published the major findings of something I am working on before my group was able to get the paper out. I don’t think I am alone in that definition, though I haven’t checked Urban Dictionary. Instead, Schuster was “scooped” because two other labs announced that they had sequenced these genomes. Uh, okay. So fucking what? According to the article, this is a devastating blow to Schuster’s group, even though they have the cacao paper submitted and they are already analyzing the Tasmanian devil sequence. My guess is that they are significantly ahead of both rivals at this stage and will get their papers out first, so why is this a big deal? Science quotes Schuster as saying:

“With what happened yesterday, I don’t believe in scientific publication anymore,” says Schuster, who thinks work shouldn’t be publicized until after peer review. “We tried to be a good citizen, … and we lost.”

You lost? What? Okay, okay, I can see how the initial big publicity would have been cool and all, but aside from a very small circle of people, who is going to remember which group made the announcement? No one. Most people will remember hearing that an announcement was made and then see the paper in a month or two and say “Hey, that chocolate genome is out. Cool.” Schuster’s group will get the citations and the other groups will be forced to publish their results in a less GlamorEleventy!!! journal and run all the comparative analysis. I guess I’m missing where Schuster “loses” here, unless this has more to do with the initial round of applause than anything else. In fact, they even get to be smug about how much further ahead they are:

The Penn State-CIRAD group sequenced the Criollo variety of cacao, assembling 76% of the cacao genome into its 10 chromosomes and placing 82% of the 28,798 genes along this DNA. “We were at the point of the [Mars-USDA] press release about 6 months ago,” claims Guiltinan.

What also seems ridiculous to me is that there are TWO groups sequencing either of these genomes. I can understand the race for the human genome and maybe even things like fruit fly and Arabidopsis, but since when did the Tasmanian devil fan club go all cut throat? And I like chocolate as much as the next person, but two genome sequences*? It’s hard to tell whether this is competition or lack of communication, but either way it seems like a giant FAIL to commit the duplicated resources. If it’s the former it’s just stupid and if the latter maybe it’s time to think about a mechanism by which people could list what genomes are being sequenced (and not in a something-I-want-to-do-one-day-and-this-is-a-way-to-pee-on-it, kinda way. Things actually on the machine.).

We also see the whole making data public before it is analyzed thing raise it’s head again.

While Schuster was fretting about his group’s Tasmanian devil work being overshadowed, his colleagues working on the cacao genome were scrambling to prevent the same thing from happening to their project. The rival Mars-USDA collaboration announced that it had assembled the sequence and opened a Web site to provide other researchers access to the data.

It’s one thing to have your own data released to the public right after assembly, but this is someone else’s data from the same organism being put out there like a Vegas buffet. I can see this being an issue, but if you are way down the road on the analysis end, don’t these announcements just light a fire to get the paper out ASAP? Statements like the one by Schuster above, might be warranted if the other groups published the data ahead of their group, but if anything, doesn’t the announcement just add some buzz to the publication?

Let’s wait for the papers before we start the pouting, no?

*BTW, the fact that Mars was a partner in the chocolate genome project (the second one) is something I find hilarious. Mmmmmm genom-nom-nom. Alright, maybe it’s just me.

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Found out

Sep 22 2010

Dear Finance Office,

I never thought you would catch me, but your diligence has paid off. To truly understand my crime, we need to go back a few years to when I was an undergrad. You see, at that time all I wanted was $46.72 worth of random supplies from Home Depot. But in my lowly life as an undergrad, this was out of my reach… so I plotted.

First, I got myself involved in research between my second and third years of college. I worked many hours of two years to produce a thesis, a couple of papers and admission to graduate school. I left my home country, family and girlfriend and went to get a PhD with a well respected member of the scientific field I wanted to pursue. It was a hard decision, but I had my eye on the prize: $46.72 in Home Depot goods.

I spent two years doing the long-distance relationship thing in different countries and time zones before I married my girlfriend, who moved to a new country with me. She knew how important my dream of Home Depot supplies was to me and I owe her a lot for being willing to move her life. After 5 years of graduate school, I had my PhD, but still no university purchasing card to abuse to my own selfish ends…. so I plotted.

I started a postdoc at a new university and started a family. I wrote grants. I wrote papers. I did research and supervised others doing research. I went to meetings and gave talks. When the time was right, I sent out job applications. LOTS of job applications. I got some interviews and some went better than others. I chose Employment University in no small part because they offered university purchasing cards.

I toiled at building up my lab for two years and even sat through your three hour ‘training’ session that was like a long winded parental speech about responsibility and how closely we would be watched. I endured much, but I was so close.

I used the Pcard for all sorts of things, diligently keeping receipts and lulling you into feeling like I was up to the task. I was never late, never lost a thing. Always crossing my t’s and dotting those i’s…. and I plotted.

Finally, I thought I had covered myself well enough to get away with a crime over a decade in the making! I went to Home Depot and carefully chose my precious items, ensuring they added to my envisioned total. I purchased them with my university card and when it went through a nearly wept in joy. I rushed out of the store, clutching my hard sought items to my chest, laughing manically. I thought I had won.

But no.

Your sharp eyes caught my missing receipt and the accusations started. You sent me emails in blue enlarged text! I knew I was doomed, and no amount of explanation was going to make up for the fact that there is no receipt. Letters were written, promises were made, and my Pcard was nearly revoked. I would estimate that ~$400 in employee time was used to rectify my egregious flaunting of the Pcard rules and regulations and I am now under double secret probation.

But for a few brief moments, as I held that $46.72 in Home Depot supplies in my hands after so much work, it all seemed worth it.

And I would have gotten away with it if it weren’t for those meddling kids.

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Repost: How day care will be the death of me

Sep 20 2010

It is merely September and I’m already on my first bought of anti-biotics. All the kids who were out of day care for the summer are back and the Wee One already has pneumonia. Of course, you would never know it, save for an occasional cough, but I’m wiped out. Seemed like a good idea to bust this post back out from just last spring.

Day care is a necessary evil if you have a two income family. Unless you have relatives close by who are willing to entertain your child while the two parents are at work, chances are you have to rely on day care. It can be expensive and a huge hassle, but there are not a lot of options.

There are good things about day care, such as your child getting to play with their peers for much of the day. This can lead to learning a lot of things they would otherwise not be confronted with at home. Children at day care also have to get used to being with non-parents for much of the day, which one could argue helps them when their parents need to leave them with someone to get something done or to go out for a night. A lot of day cares also go to great lengths to take what is understood about how children learn and incorporate that into daily activities. All of these are good things.

But daycare has another effect on your life. Before we sent the Wee One to daycare she almost never got sick.

BERJAYA
The Wee One, before day care.

We had the normal run of one or two colds a winter as a household, but nothing major. But day care changed all that. Day care is apparently where every cold and flu goes to party. It’s like the runny nose equivalent of Burning Man and we have our very own vector from that source. It’s like living with the monkey from “Outbreak”.

BERJAYA
The Wee One in day care. This is actually the look we get every afternoon when we arrive to take her home.

This winter the family has been a revolving door for colds. Every time one sweeps through and leaves us for dead, there is another one at the door. I’m pretty sure I have been healthy for a grand total of 8 days since November and my wife has been hit harder by each cold than I have. Day care is probably taking a year off of our lives, and we’re not even getting to play with play dough! The thing I am most excited about this spring is the chance that the time between colds will lengthen as the days do.

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