> I was looking into it further…this is one example I found (of many) of actual geneticists expressing it the same way as these folks. It seems like a pretty standard way to write it.

Depends on what you mean by standard, I guess. However, in either case it is incorrect, and I gave you an article literally published by Jax, which is the ultimate authority on both these animals and their nomenclature, saying as much.

It’s pretty standard for academics and practitioners to refer to lactate as “lactic acid”, and to think of it as a waste product, and yet both of these notions are totally incorrect.

> Especially when a cursory search of Jackson’s catalog seems to indicate that their Ifngr1-/- mice are all C57BL/6J.

You’re a little confused on the terminology here, which is understandable because these databases assume proficiency in it. Ifngr1 is a gene, not a strain (interferon gamma receptor 1). The “-/-“ refers to a double-knockout. Jax produces 6J-background mice with a huge number of knockouts/knockins/mutations, they supply over 8,000 strains and most are built on 6J. If you search the database for the string “ifngr1” you will see many substrains with that string in their denotation. The correct notation for ifngr1 double knockouts is probably B6.129S7-Ifngr^(1tm1Agt)/J, where “J” refers to the colony maintainer (in this case, Jackson Laboratories), the post-hyphen string refers to the gene of interest, and “tm” denotes the targeted mutation of that gene. B6.129S is a 129 substrain commonly used when producing congenic strains.

But, again, I don’t actually know if that’s the correct strain because they didn’t actually give the right notation.

> To me, questions of whether these were the best test subjects seem more pertinent than potential ambiguity in terminology

They’re the same question, and that’s my point. People don’t get that the ambiguity impairs our ability to correctly evaluate the comparisons being made between these subjects. A mouse denoted as “C57BL/6” in your study could literally be one of several thousand strains, with tens of thousands of known and documented mutations which may of may not be present in your cohort, which is to say nothing of the undocumented influence of drift.

As to whether they’re the best subjects, the unfortunate fact is that we don’t really have an alternative genetic background anywhere near as standardized as these animals. The problem is that nutrition has a habit of trying to shift the reference frame to make low quality data and inferences look high-quality simply because it’s the best they have. See the GRADE scandal for a key example of this.

> Is there more reason to suggest they should have specified?

Geneticists understand that using rodents as a test subject not only means you need to take a huge grain of salt when comparing macroscopic results to humans, but that we also need a big grain of salt when comparing mice cohorts to other mice cohorts, at least when they are of different genotypes.

It just depends on how confident you are that all accumulated drift and mutations in all existing laboratory mice of each denoted strain have have zero effect on the physiology of the animals. Personally, my confidence in this is zero.

If you want, I can give you recent literature on this issue of growing, undocumented genetic diversity in common lab strains and why it’s a problem.

> Anyway I’ll stick with my Cardiologist and my Oncologist at Ironwood Cancer Research Center because they’ve been correct through all of my treatments thus far to cure my Lymphoma faster than the first quacks at Banner (Who I will never go to again) who I got stuck with, and that was 7 years ago.

Cool. I don’t care. You making conclusive claims in a subreddit that requires you to cite claims.

First off, you’re in /r/science. If you want to make claims, be ready to cite them without getting snarky with people, particularly if you aren’t actually educated on the topic.

Second, the cholesterol-lowering effect sometimes seen in research involving oatmeal is from soluble fiber. Guess how many grams of soluble fiber are in each 20g-carbohydrate packet of Quaker instant oatmeal? I’ll give you a hint: it’s less than 2g and more than 0g. This is a minuscule amount.

> and for maintaining plasticity of inner walls of arteries and veins by aiding on the prevention of hardening and plaque

Cardiovascular disease is the number one cause of death in the developed world. If this statement was true, Quaker would be preaching it 24/7 on every advertising channel they could get their hands on. Alas, they are not.

> Quaker instant oatmeal is “processed” food but is actually quite good for you

Source?

There is an unfortunate general ignorance outside of genetics of what these mice really are and how to think about them. Institutions that have their own colonies with have qualified and knowledgeable people as maintainers, but they aren’t writing the papers. In a nutshell, they are the renewable testing grounds of a genome we know and control, making them a valid background for a) interventions in that genome and b) interventions among genetically identical cohorts.

Black-6 descendant strains (like B6J, which this study likely used) are not intended to ask questions of diet or drug effect and extrapolate across non-identical colonies or other species, but rather to have a controlled genetic background against which to test the effect of interventions and/or genes which we add or subtract, ie knockouts.

The way that Jackson maintains B6J is by periodically reintroducing frozen gametes from the original “Adam and Eve” B6J pair, and using them to refresh the source colony based on the reference genome, which for B6J is called GRCm38.p6.

However, the inevitable fact is that as soon as you take mice away from that colony and start breeding them, they immediately start diverging from the source genome, accumulating mutations which have the potential to alter their physiology and bias study results. This is why it’s so critically important that you always denote the exact substrain being used, but also more broadly that we take a huge grain of salt when we see some change in outcomes in a mouse population for which we don’t really have an precise background rate of that outcome. It’s not exactly the cohort that’s the problem, since if you’re using two groups of mice that are presumably nearly genetically identical to each other the deviation is null, but rather the comparison between studies.

eg, study 1 used “Black-6” mice and found diet A had 1.5 OR for some outcome compared to diet B, study 2 used “Black-6” mice and found diet A had 0.9 OR for the same outcome compared to diet B, but if we have no idea what the actual genetic differences between those two colonies were, the comparison is kinda fucked. We don’t know their distance from the reference genome, if the distance from each is symmetrical, if both have had cryorecovery done and at what points, etc. These mice are under intense selection pressure to breed large litters and survive a very unnatural laboratory environment, and we know there are substantial genetic differences accumulating among them, both from those environmental stimuli and from drift. And then you start bundling these things into meta-analysis and you have this growing source of invisible confounding.

> We first examined feeding behavior and multiple physiological parameters in naive wild-type (WT) C57BL6 female mice placed on either a chow or an AIN93G diet for 4 weeks.

There is no such thing as a “C57BL6” mouse, unless you have a time machine and are going back to Jackson in the 1950’s and grabbing some of the initial black-6 population. Otherwise, you are using some other substrain that needs to be denoted so we know how to evaluate their outcomes.

https://www.jax.org/news-and-insights/jax-blog/2016/june/there-is-no-such-thing-as-a-b6-mouse

Source: Jackson Lab, the global supplier of genetically defined mice, including the strain incorrectly denoted on this paper, and the substrain they actually did use

Citation for this?

Not a well-studied question. Resistance training seems to reliably increase some factors within BMD (mainly sclerostin and osteocalcin) but the increases are generally clinically insignificant, ie they aren’t big enough to even budge the osteoporotic fracture risk calculation.

This highlights why resistance training and adequate bioavailable bone minerals are so critically important during development. For the most part, once you’re 30 maintenance is really the name of the game.

Not specifically related, but Stephan Schiffels (one of the lead authors) runs the Population Genetics group at Planck and has published lots of really great work in this area if anyone wants further reading.

Not really. We are under no delusion that a complete phylogenetic tree will ever be mapped, there’s just too many species across too much time, and astronomically low chances of preservation, not to mention large stretches all over the tree where body plans simply aren’t preservable. It’s indeed an often misused term, but it’s a useful one in the right context, where you have a distinct intermediary (Darwin in fact used the term “intermediary links”, not “‘missing”) whose ancestors and descendants share morphology you can place on a continuum, with the intermediary somewhere in between.