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tdcapellini.bsky.social @tdcapellini.bsky.social · 6d

In the sadness I feel for the passing of Jane Goodall, I take from her a continued energy, passion, and commitment to bolster up, fight for, and inspire those without voices! We must be champions to protect this earth and basic decency!

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tdcapellini.bsky.social @tdcapellini.bsky.social · 11d

Question for those at academic research institutions: Have your institutions received requests from the federal government regarding recent changes in Restricted Party and Export Controls Screening Process?

tdcapellini.bsky.social @tdcapellini.bsky.social · 13d

Kirstin Sterner (University of Oregon) and I would like to give a big CONGRATULATIONS to Dr. Sam Queeno, who successfully defended her dissertation entitled "A New Perspective on Human Bipedalism: Using Functional Genomics as a Window to Past Physiology". Terrific Job Sam!!!!

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Reposted

Daniel Aldrich @danielaldrich.bsky.social · 20d

This was a 9-0 decision last year

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tdcapellini.bsky.social @tdcapellini.bsky.social · Sep 3

Thanks Michael! This was lots of fun to work on! My post-doc Gayani is terrific (and now on the job market if there are group leader positions in Germany)

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tdcapellini.bsky.social @tdcapellini.bsky.social · Aug 29

Thanks Venki!!

tdcapellini.bsky.social @tdcapellini.bsky.social · Aug 29

We want to thank the NIH for providing federal funding for this work. And we note here that this grant was illegally terminated by the federal administration causing future studies on the manner in which these changes influence human disease risk and birth process to be ended.

tdcapellini.bsky.social @tdcapellini.bsky.social · Aug 29

We want to thank the individuals who consented to provide human samples as they appreciate that knowledge is critical to understanding the human condition including our derived disease risks.

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tdcapellini.bsky.social @tdcapellini.bsky.social · Aug 29

We want to thank the Birth Defects Research Laboratory at the University of Washington for their assistance in ethically collecting human samples.

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tdcapellini.bsky.social @tdcapellini.bsky.social · Aug 29

We want to thank the following scientists/staff/curators for their help: N Shubin, J Hanken (MCZ), M Gage (MCZ), S Turney (MCZ), B Zimkus (MCZ), J Woodward (MCZ), J Austiff (MCZ), J Chaumel (MCZ), T Stewart, E Hoeger (AMNH), M Surovy (AMNH), L Caspers (AMNH)

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tdcapellini.bsky.social @tdcapellini.bsky.social · Aug 29

Overall, we argue that the ilium is part of highly important adaptive musculoskeletal pelvic complex that is
shaped during evolution under the constraints of complex polygenic underpinnings.

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tdcapellini.bsky.social @tdcapellini.bsky.social · Aug 29

Third, the reorientation of the growth plate, and subsequent changes in ossification, now cause a hip joint to face more anterior/ventral, and this might lead to greater loading issues on the femoral head/neck and increased rise of hip disease.

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tdcapellini.bsky.social @tdcapellini.bsky.social · Aug 29

Likewise, obstetrical-dilemma models that attempt to model the human pelvis as resulting from a chimp-like pattern of growth may be off. And this critical shift will have different relationships to permitting or constraining later human brain growth and in relationship to bipedalism.

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tdcapellini.bsky.social @tdcapellini.bsky.social · Aug 29

Second, that this growth plate shift, preceded human brain expansion and thus a widened canal configuration due to iliac bones growing in a different plane may have been a prerequisite and may have permitted later brain expansion in humans.

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tdcapellini.bsky.social @tdcapellini.bsky.social · Aug 29

This growth plate shift occurred likely at the base of many hominins indicating that the adaptive radiation of hominins from 4.5-2.5 MYA might have resulted from the benefits this structural innovation had to bipedalism.

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tdcapellini.bsky.social @tdcapellini.bsky.social · Aug 29

Nevertheless, we argue that it is unlikely a single gene of large effect but many regulatory changes that facilitated this shift.

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tdcapellini.bsky.social @tdcapellini.bsky.social · Aug 29

First, that major structural innovations, a kin to bat wings, have actually occurred in human evolution and during a key window when natural selection appeared to favor efficiency in bipedalism. Whether this shift was markedly rapid or more gradual during this 8-4.5 MY period remains unclear.

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tdcapellini.bsky.social @tdcapellini.bsky.social · Aug 29

What are the ramifications of these major shifts?

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tdcapellini.bsky.social @tdcapellini.bsky.social · Aug 29

This indicates that the musculoskeletal ilium was subject to intense selection to shape the pelvis, with the role of muscle induction on pelvis shape likely in utero.

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tdcapellini.bsky.social @tdcapellini.bsky.social · Aug 29

We finally discovered that around the time when the iliac growth plate shift occurs, muscles critical for walking (medius/minimus and rectus femoris) are already attached to the cartilage, and regulatory elements specific to muscle and perimysium show markedly evidence of HAR enrichment.

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tdcapellini.bsky.social @tdcapellini.bsky.social · Aug 29

Overall, these two ilium shifts (cartilage reorientation and bone timing/locational shift) allow the human pelvis to form early and maintain its critical shape. And this process has been under polygenic selection.

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tdcapellini.bsky.social @tdcapellini.bsky.social · Aug 29

One key regulatory sequence specific to the ilium and near RUNX2 harbors a HAR and this drives strong external ossifying cell expression (not internally) in the mouse model with the chimp version not active.

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tdcapellini.bsky.social @tdcapellini.bsky.social · Aug 29

Using network analyses we reveal a key perichondrium/osteoblast network where many genes with roles in pelvis ossification are hit by HARs including RUNX2 and FOXP1/2, with mutations in human coding regions in these genes altering human and mouse ossification.

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tdcapellini.bsky.social @tdcapellini.bsky.social · Aug 29

Moreover, in living humans, these same regulatory sequences and others specific to this human ossification phenotype have reduced genetic variation in humans, indicative of the effects of purifying selection on this critical shape phenotype.

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tdcapellini.bsky.social @tdcapellini.bsky.social · Aug 29

Using spatial transcriptomics and single cell epigenomics, we then reveal in humans at the key moment of these bone shifts, that osteoblast cell type-specific regulatory elements harbor tens to hundreds of HARs once again indicating this shift is highly polygenic.

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