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Cameron Hill @cameronhill13.bsky.social · 1d

Excited to share our preprint using time-resolved small-angle X-ray diffraction to study myosin motor conformations during isometric twitch and tetanus contractions in the slow-twitch rat soleus skeletal muscle #myoblue

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Reposted by Cameron Hill

European Society for Muscle Research Early Careers Association @esmreca.bsky.social · May 29

There is still time for ECA members to apply for travel awards to #EMC2025. Applications are now being recieved until 06/06/25

European Society for Muscle Research Early Careers Association @esmreca.bsky.social · Apr 29

The European Muscle Conference 2025 website is now live!
www.emc2025amsterdam.com

The ECA have a number of travel awards available for ECR's attending. We will be hosting an online meeting on 14/05/25 at 1600 CET to provide further information about the travel awards, so come along for more info

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Reposted by Cameron Hill

European Society for Muscle Research Early Careers Association @esmreca.bsky.social · Apr 29

The European Muscle Conference 2025 website is now live!
www.emc2025amsterdam.com

The ECA have a number of travel awards available for ECR's attending. We will be hosting an online meeting on 14/05/25 at 1600 CET to provide further information about the travel awards, so come along for more info

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Cameron Hill @cameronhill13.bsky.social · Apr 29

This is really cool, congratulations! Was there any indication of a change in resting I1,1/I1,0 in the T2DM group?

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Cameron Hill @cameronhill13.bsky.social · Apr 29

Some really kind words and interesting perspectives from @hesselanthony.bsky.social on our paper published in @pnas.org. (www.pnas.org/doi/10.1073/...). Anthony sheds some light on why there are exciting times ahead for the muscle X-ray diffraction community!

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Cameron Hill @cameronhill13.bsky.social · Mar 18

I've just had a paper published which uses cartoons of the thick and thin filaments that may also be helpful to explain how muscle X-ray people use each part of the X-ray patterns to ascribe to certain sarcomere structures and how they change with contraction:
www.pnas.org/doi/10.1073/...

PNAS

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans...

www.pnas.org

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Reposted by Cameron Hill

Avery Hinks @hinksave.bsky.social · Mar 11

The final piece of the puzzle for my PhD thesis, currently under review.

We looked at the trajectory of age-related serial sarcomere loss across young (8 mo), middle-aged (20 mo), old (32 mo), and very old rats (36 mo) in 5 different muscles. A simple study but it provided a lot of cool insight!

Geoff Power @geoffpower.bsky.social · Mar 11

We investigated serial sarcomere loss as a contributor to the age-related loss of muscle mass across four aging timepoints

SSN loss contributed to the loss of muscle mass. Increasing SSN is a target for improving muscle performance in old age. @hinksave.bsky.social

www.biorxiv.org/content/10.1...

Changes in serial sarcomere number of five hindlimb muscles across adult aging in rats

Introduction: Aging is associated with a reduction in muscle fascicle length (FL), which contributes to sarcopenia: the age-related loss of muscle mass and function. Studies on rodents have confirmed ...

www.biorxiv.org

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Cameron Hill @cameronhill13.bsky.social · Mar 13

For a bite-sized summary of our main findings @esrf.fr have kindly written a brief overview of our paper:
www.esrf.fr/home/news/ge...
#myoblue

A game of load and calcium determines muscle relaxation

www.esrf.fr

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Cameron Hill @cameronhill13.bsky.social · Mar 13

To summarise, removing load is more effective at relaxing the muscle than Ca2+. When Ca2+ is removed, a conformational change in troponin may initiate the initial detachment of myosin from actin. Yielding of weak sarcomeres and tendon compliances determine muscle relaxation.

Cameron Hill @cameronhill13.bsky.social · Mar 13

When examining sarcomere length, SL remains constant during the first isometric phase of relaxation (blue). When force starts to decline, weak sarcomeres being to yield and stretch as identified by two populations of sarcomeres, eventually resulting in exponential force decay.

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Cameron Hill @cameronhill13.bsky.social · Mar 13

In this period called "isometric relaxation" motors begin to detach as signalled by a decrease in the equatorial intensity ratio as myosin moves away from actin (blue), meaning the strain per attached motor increases.

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Cameron Hill @cameronhill13.bsky.social · Mar 13

If both the thick and thin filaments are remaining ON given the high load and low Ca2+ after electrical stimulation, how does myosin escape their actin-attached, force-generating state?

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Cameron Hill @cameronhill13.bsky.social · Mar 13

IAL2 increases as motors attach to actin and tropomyosin moves into the actin grooves. When load is removed and myosin detaches, IAL2 ↓ despite the high Ca2+ as tropomyosin is allowed to move out of the grooves between actin. When Ca2+ ↓, the change in IAL2 is similar to force.

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Cameron Hill @cameronhill13.bsky.social · Mar 13

When load is removed (grey shade) the thick filament begins to switch off as motors detach, and occurs much faster than force due to the small number of motors required to drive shortening. When Ca2+ is removed IML1 remains low (blue shade) and slowly returns to its OFF state.

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Cameron Hill @cameronhill13.bsky.social · Mar 13

X-ray diffraction patterns were collected and reflections ascribed to certain sarcomere structures. (See ALT text for description of each reflection examined). I want to draw attention to two reflections in particular - the ML1 and AL2 reflections.

$X-ray diffraction patterns of mouse skeletal muscle. The right picture is a difference pattern of contracting minus resting. 1,0 & 1,1 - equatorial reflections associated with the hexagonal lattice arrangement of the thick and thin filaments M3 - the third-order meridional reflection associated with the ~14.34nm axial repeat of myosin motors M6 - The sixth-order meridional reflection associated with the ~7.17nm axial repeat of the thick filament backbone M11 - The eleventh-order meridional reflection associated with the ~3.9nm axial repeat of A-band titin ML1/AL1 - The mixed first-order myosin and actin layer lines. ML1 is associated with the ~43nm helical repeat of myosin motors whilst AL1 is associated with the ~37nm helical repeat of actin helices AL2 - The second-order actin layer line associated with the azimuthal position of tropomyosin in the thin filament. This reflection is incredibly weak at rest and intensifies on contraction. AL6 & AL7 - The sixth- and seventh-order actin layer lines associated with the genetic helices of actin of axial spacing ~5.9nm and ~5.1nm respectively$ The quasi-helical repeat of myosin motors is denoted by the first-order myosin layer line (ML1). A decrease in the intensity of this reflection indicated motors leaving their helically ordered OFF state, thus signalling an ON thick filament

The quasi-helical repeat of myosin motors is denoted by the first-order myosin layer line (ML1). A decrease in the intensity of this reflection indicated motors leaving their helically ordered OFF state, thus signalling an ON thick filament

The intensity of the second actin layer line (AL2) corresponds to the azimuthal position of tropomyosin in the thin filaments. In resting muscle (OFF) tropomyosin blocks the binding sites on actin for myosin, but when the thin filament is switched ON by myosin binding to actin, tropomyosin moves into the grooves between the two actin filaments, resulting in an increase in the intensity of this reflection.

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Cameron Hill @cameronhill13.bsky.social · Mar 13

To test this, we visited ID02 at
@esrf.fr to perform time-resolved X-ray diffraction on mouse EDL muscles. To separate out the contribution of load and [Ca2+]i we imposed ramp shortening to remove load when [Ca2+]i was high, and by allowing reuptake of Ca2+ by the SR.

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Cameron Hill @cameronhill13.bsky.social · Mar 13

This paradox poses a fundamental question: how does a muscle relax following contraction given the above paradox of high load and actin-bound motors preventing the thin filament switching off

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Cameron Hill @cameronhill13.bsky.social · Mar 13

Muscle relaxation has been long viewed as a reversal of this activation paradigm, but actin-bound myosin motors prevent the return of tropomyosin back to the "blocked" position, suggesting that motor detachment rather than Ca2+ dissociation may be a key determinant of relaxation.

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Cameron Hill @cameronhill13.bsky.social · Mar 13

When [Ca2+]i increases on electrical stimulation, troponin becomes saturated with Ca2+ triggering a movement of troponin and tropomyosin exposing binding sites. Motors then leave their helical tracks in a load-dependent manner. High load + mechanosensing = rapid activation.

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Cameron Hill @cameronhill13.bsky.social · Mar 13

In resting muscle myosin motors in the thick filaments are arranged in an OFF state unavailable for actin binding, with a tiny fraction of sentinel motors. Troponin and tropomyosin in the actin-containing thin filaments are also OFF at low [Ca2+]i, preventing myosin binding.

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Cameron Hill @cameronhill13.bsky.social · Mar 13

This has been a long time in the making but I am absolutely delighted to share our latest paper published in
@pnas.org where we use time-resolved X-ray diffraction to elucidate the regulatory roles of the thick and thin filaments during muscle relaxation #myoblue
www.pnas.org/doi/10.1073/...

Dual-filament regulation of relaxation in mammalian fast skeletal muscle | PNAS

Muscle contraction is driven by myosin motors from the thick filaments pulling on the actin-containing thin filaments of the sarcomere, and it is r...

www.pnas.org

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Reposted by Cameron Hill

European Society for Muscle Research Early Careers Association @esmreca.bsky.social · Feb 27

The meeting can be accessed via the below link:

duke.zoom.us/j/91574693682 (Meeting ID: 915 7469 3682)

Join our Cloud HD Video Meeting

Zoom is the leader in modern enterprise video communications, with an easy, reliable cloud platform for video and audio conferencing, chat, and webinars across mobile, desktop, and room systems. Zoom ...

duke.zoom.us

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Reposted by Cameron Hill

European Society for Muscle Research Early Careers Association @esmreca.bsky.social · Feb 27

The Early Careers Association of the European Society for Muscle Research invite you to join us for our 5th annual ECA online event titled "Muscle Research Between Academia and Industry" with talks from Dr Sinead Roberts @sineadrobert and Dr Valentin Burkart on 26th March 2025 at 1600 CET

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Reposted by Cameron Hill

Anthony Hessel, PhD @hesselanthony.bsky.social · Dec 16

🚨📢Paper alert! Real progress on identifying why residual force enhancement occurs in skeletal muscle! This was a study I dreamed about since grad school. Please share! 🔬💪🧪

www.pnas.org/doi/10.1073/...

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Cameron Hill @cameronhill13.bsky.social · Nov 20

#MyoBlue