Stay in your bubble, rusty joints, and ant venom

I’m doing something new this morning and only hitting articles where the entire article is available and not behind a paywall. Barring some ground-shaking research, I intend to stick to that going forward. I’m also using the more popular science cover articles from journals like Science and Nature where it’s available rather than leaping straight into the underlying papers.

Medicine and Health

Nature: Detailed genetic screening looks at genes responsible for breast cancer

A massive study of nearly  4,000 variants in a gene associated with cancer could help to pinpoint people at risk for breast or ovarian tumours. …

The American College of Medical Genetics and Genomics recognizes about 60 genes for which screening might suggest a medical plan  to prevent or reduce the effects of a disease. Yet often when people find out that their genes include unusual DNA sequences , they are at a loss to interpret that finding.

This wasn’t just picking up on how many people had genes that were indicative of breast cancer. Instead it was a deep dive in which researchers “covered nearly every  possible single-letter variation” in some of these genes and correlated results with lab data. As many people have learned, it’s quite possible to have one of the genes associated with cancer risk, and never develop cancer. This study helps nail down exactly how 

Nature: CRISPR editing done in a living mice without detectable unwanted mutations

Here we describe ‘verification of in vivo off-targets’ (VIVO), a highly sensitive strategy that can robustly identify the genome-wide off-target effects of CRISPR–Cas nucleases in vivo. We use VIVO and a guide RNA deliberately designed to be promiscuous to show that CRISPR–Cas nucleases can induce substantial off-target mutations in mouse livers in vivo. More importantly, we also use VIVO to show that appropriately designed guide RNAs can direct efficient in vivo editing in mouse livers with no detectable off-target mutations. VIVO provides a general strategy for defining and quantifying the off-target effects of gene-editing nucleases in whole organisms, thereby providing a blueprint to foster the development of therapeutic strategies that use in vivo gene editing.

Recently, some doubt has been cast on CRISPR’s potential after several experiments showed a lot of unplanned mutations resulting from some incomplete gene clipping / joining. This experiment showing apparently error-free editing in a living organism is a big step.

Science: Is arthritis caused by oxidation?

Osteoarthritis is the most common joint disorder with increasing global prevalence due to aging of the population. Current therapy is limited to symptom relief, yet there is no cure. Its multifactorial etiology includes oxidative stress and overproduction of reactive oxygen species, but the regulation of these processes in the joint is insufficiently understood. We report that ANP32A protects the cartilage against oxidative stress, preventing osteoarthritis development and disease progression.  … Our findings indicate that modulating ANP32A signaling could help manage oxidative stress in cartilage, brain, and bone with therapeutic implications for osteoarthritis, neurological disease, and osteoporosis.

You’re not getting older. Your joints are getting rusty.


PNAS: Did climate change drive the transition from Neanderthals to modern humans?

 A causality between millennial-scale climate cycles and the replacement of Neanderthals by modern humans in Europe has tentatively been suggested. However, that replacement was diachronous and occurred over several such cycles. A poorly constrained continental paleoclimate framework has hindered identification of any inherent causality. Speleothems from the Carpathians reveal that, between 44,000 and 40,000 years ago, a sequence of stadials with severely cold and arid conditions caused successive regional Neanderthal depopulation intervals across Europe and facilitated staggered repopulation by modern humans. Repetitive depopulation–repopulation cycles may have facilitated multiple genetic turnover in Europe between 44,000 and 34,000 years ago.

Yeah, that’s an unusually and intentionally dense opening. I will translate — until now, it’s been really hard to tell if climate change is connected with the transition from Neanderthals to modern humans. Partly that’s because we haven’t had a good picture of climate change beyond the broad strokes. Now some cave formations in the Carpathians are showing that the environment bounced around severely over a period that seems pretty closely aligned with the time when Neanderthals started losing their grip over much of the continent.

Nature: The world’s oldest artwork is a ‘crayon doodle’

Sometime in the Stone Age, human artists began experimenting with a new form of visual art: drawing. Now, from the ancient rubble that accumulated on the floor of a South African cave comes the earliest-known example — an abstract, crayon-on-stone piece created about 73,000 years ago.

If you’re thinking that Crayola might not have been making genuine crayons at that point, not even in burnt sienna, you’re correct.

Now scientists know the Stone Age cave-dwellers liked to draw, too. In 73,000-year-old deposits at the site, Henshilwood and his colleagues discovered a four-centimetre-long pebble criss-crossed with nine lines. The lines appear to have been drawn with an ochre crayon, rather than painted on the surface. The artwork has given researchers their first insight into how Blombos cave’s prehistoric inhabitants used ochre as a pigment.


Science: An analysis of Bull Ant venom

Ants are diverse and ubiquitous, and their ability to sting is familiar to many of us. However, their venoms remain largely unstudied. We provide the first comprehensive characterization of a polypeptidic ant venom, that of the giant red bull ant, Myrmecia gulosa. We reveal a suite of novel peptides with a range of posttranslational modifications, including disulfide bond formation, dimerization, and glycosylation.

Some of these compounds turned out to be effective at knocking out other insects, making them pretty good for hunting or defense. But in general the thing to understand is that they cause just astounding levels of dammitthathurts.

Materials Science

PNAS: Making ceramics both tougher and stronger at the same time

Topologically interlocked materials (TIMs) are an emerging class of architectured materials based on stiff building blocks of well-controlled geometries which can slide, rotate, or interlock collectively providing a wealth of tunable mechanisms, precise structural properties, and functionalities. TIMs are typically 10 times more impact resistant than their monolithic form, but this improvement usually comes at the expense of strength.

Strength and toughness may sound like the same thing, but to a materials scientist, they’re not. The best shorthand here is how easily something breaks vs how easily its crushed. Glass is actually quite strong in one sense, but obviously fragile in the other. Ceramics have a fantastic number of uses, but can tend to be fragile — that is, easily broken. The “not tough” part of the equation.  But making them tougher can make them less strong, more easily crushed or unable to hold up to continuous stress. So a system that makes possible ceramics that are both strong and tough is a good thing.


PNAS: People hate making decisions when they don’t understand the rules or data is ambiguous

In statistics, control theory, decision theory, and economics, the question of how to cope with subjective uncertainty comes into play. While researchers have developed many different approaches, it is standard in decision theory to impose axioms on preferences over choices. Axiomatic decision theory justifies representations of preferences that provide applied researchers with alternative ways to capture uncertainty responses. In applications, however, a decision maker must decide how to calibrate preference parameters, including aversion to ambiguity, and to model misspecification. 

One place this shows up all the time: Polls. People are constantly being asked questions in polls where they feel like they don’t know enough or where even the people taking the poll may feel the questions are misleading. Unsurprisingly — people don’t like that. Also not unsurprisingly — the results of people being forced to make decisions on ambiguous data or in systems with poorly defined rules turn out to be … poorly defined. This is one of those reports that may generate and immediate “duh,” but it actually has broad implications. Because there are a huge number of ways, from operating equipment to casting a vote, where people are operating with bad data or under circumstances where they feel the “model” isn’t right. Being able to better understand how people act under those conditions would be a good thing.

PNAS: Mapping emotions in the brain

Subjective feelings are a central feature of human life. We defined the organization and determinants of a feeling space involving 100 core feelings that ranged from cognitive and affective processes to somatic sensations and common illnesses. The feeling space was determined by a combination of basic dimension rating, similarity mapping, bodily sensation mapping, and neuroimaging meta-analysis.

Honestly, this one is so incomprehensible to me that it makes me feel … some of what the people in the bad-decisions study must have been feeling. I didn’t even know there were “100 core feelings.” Let’s see blazing anger at Trump, that’s one. Deep seated anger at Trump. Two. Grinding resentment at Trump


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