In the reductionistic approach that dominates science, we've tried to categorize even our own physiology into sperate systems such as the immune system or the metabolic system. A number of beautiful papers show that things are not so segmented as we might think. A thread.

1/

Already almost a decade ago, a brilliant paper in Nature showed that there is crosstalk between the gut microbiome, gut epithelial cells, and immune cells. Moreover, it showed that epithelial cells can take over the immune cell function.
https://t.co/SI1Lqzj445

2/
Than there is this work of art:
https://t.co/O38Gm3P1Nu
The author argues that the immune and metabolic system are likely coevolved and demonstrates that cytokines in fact also act as metabolic hormones. This explains the low-grade inflammation associated with e.g. diabetes.

3/
A quote:
"The evolutionary advantages of a strong defence system
are obvious [...] As a strong immune response is dependent on energy sources, one can also argue that the integration of these systems and their cooperation [...] would be highly advantageous."

4/
"From this perspective, an intriguing way to think about this paradigm would be to envision immune mediators, such as cytokines,
as metabolic hormones. In fact, this aspect of immunometabolism is
extremely well-conserved among organisms"

5/
On the author's website the supplementary data includes long lists of evidence that cytokines such as IL-6 and TNF have metabolic effects:
https://t.co/pSUf09kyvZ

6/
The further researchers dig, the more complex things turn out to be. This intriguing paper, published two weeks ago, identifies nerve cells residing in the gut that *autonomously* can regulate blood glucose and insulin:
https://t.co/OxF3x9aqt4

7/
It shows that insulin respons is not only centrally regulated. It is autonomously regulated from within the gut as well, responding to bacterial impulses.

8/
The take home message:
Glycemic response is not just a simple feedback loop acting upon carb intake, the gut microbiome as well as the immune system have a direct roles in metabolic regulation as well.

9/end

More from Science

https://t.co/hXlo8qgkD0
Look like that they got a classical case of PCR Cross-Contamination.
They had 2 fabricated samples (SRX9714436 and SRX9714921) on the same PCR run. Alongside with Lung07. They did not perform metagenomic sequencing on the “feces” and they did not get


A positive oral or anal swab from anywhere in their sampling. Feces came from anus and if these were positive the anal swabs must also be positive. Clearly it got there after the NA have been extracted and were from the very low-level degraded RNA which were mutagenized from

The Taq.
https://t.co/yKXCgiT29w to see SRX9714921 and SRX9714436.
Human+Mouse in the positive SRA, human in both of them. Seeing human+mouse in identical proportions across 3 different sequencers (PRJNA573298, A22, SEX9714436) are pretty straight indication that the originals

Were already contaminated with Human and mouse from the very beginning, and that this contamination is due to dishonesty in the sample handling process which prescribe a spiking of samples in ACE2-HEK293T/A549, VERO E6 and Human lung xenograft mouse.

The “lineages” they claimed to have found aren’t mutational lineages at all—all the mutations they see on these sequences were unique to that specific sequence, and are the result of RNA degradation and from the Taq polymerase errors accumulated from the nested PCR process
Hard agree. And if this is useful, let me share something that often gets omitted (not by @kakape).

Variants always emerge, & are not good or bad, but expected. The challenge is figuring out which variants are bad, and that can't be done with sequence alone.


You can't just look at a sequence and say, "Aha! A mutation in spike. This must be more transmissible or can evade antibody neutralization." Sure, we can use computational models to try and predict the functional consequence of a given mutation, but models are often wrong.

The virus acquires mutations randomly every time it replicates. Many mutations don't change the virus at all. Others may change it in a way that have no consequences for human transmission or disease. But you can't tell just looking at sequence alone.

In order to determine the functional impact of a mutation, you need to actually do experiments. You can look at some effects in cell culture, but to address questions relating to transmission or disease, you have to use animal models.

The reason people were concerned initially about B.1.1.7 is because of epidemiological evidence showing that it rapidly became dominant in one area. More rapidly that could be explained unless it had some kind of advantage that allowed it to outcompete other circulating variants.

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