In a study published on May 25, 2021, in Nature Communications, the investigators showed that using these compounds increased the regeneration of muscle cells in mice by activating the precursors of muscle cells, called myogenic progenitors. Although more work is needed before this approach can be applied in humans, the research provides insight into the underlying mechanisms related to muscle regeneration and growth and could one day help athletes as well as aging adults regenerate tissue more effectively.

“Loss of these progenitors has been connected to age-related muscle degeneration,” says Salk Professor Juan Carlos Izpisua Belmonte, the paper’s senior author. “Our study uncovers specific factors that are able to accelerate muscle regeneration, as well as revealing the mechanism by which this occurred.”

The compounds used in the study are often called Yamanaka factors after the Japanese scientist who discovered them. Yamanaka factors are a combination of proteins (called transcription factors) that control how DNA is copied for translation into other proteins. In lab research, they are used to convert specialized cells, like skin cells, into more stem-cell-like cells that are pluripotent, which means they have the ability to become many different types of cells.

“Our laboratory previously showed that these factors can rejuvenate cells and promote tissue regeneration in live animals,” says first author Chao Wang, a postdoctoral fellow in the Izpisua Belmonte lab. “But how this happens was not previously known.”

Muscle regeneration is mediated by muscle stem cells, also called satellite cells. Satellite cells are located in a niche between a layer of connective tissue (basal lamina) and muscle fibers (myofibers). In this study, the team used two different mouse models to pinpoint the muscle stem-cell-specific or niche-specific changes following addition of Yamanaka factors. They focused on younger mice to study the effects of the factors independent of age.

In the myofiber-specific model, they found that adding the Yamanaka factors accelerated muscle regeneration in mice by reducing the levels of a protein called Wnt4 in the niche, which in turn activated the satellite cells. By contrast, in the satellite-cell-specific model, Yamanaka factors did not activate satellite cells and did not improve muscle regeneration, suggesting that Wnt4 plays a vital role in muscle regeneration.

According to Izpisua Belmonte, who holds the Roger Guillemin Chair, the observations from this study could eventually lead to new treatments by targeting Wnt4.

“Our laboratory has recently developed novel gene-editing technologies that could be used to accelerate muscle recovery after injury and improve muscle function,” he says. “We could potentially use this technology to either directly reduce Wnt4 levels in skeletal muscle or to block the communication between Wnt4 and muscle stem cells.”

The investigators are also studying other ways to rejuvenate cells, including using mRNA and genetic engineering. These techniques could eventually lead to new approaches to boost tissue and organ regeneration.

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Materials provided by Salk Institute. Note: Content may be edited for style and length.

“Adherence to coding standards is rarely considered in scientific software, although it can even lead to incorrect scientific results,” says Professor Alexandros Stamatakis, who works both at HITS and at the Institute of Theoretical Informatics (ITI) of KIT. The open-source SoftWipe software tool provides a fast, reliable, and cost-effective approach to addressing this problem by automatically assessing adherence to software development standards. Besides designing the above-mentioned tool, the computer scientists benchmarked 48 scientific software tools from different research areas, to assess to which degree they met coding standards.

“SoftWipe can also be used in the review process of scientific software and support the software selection process,” adds Adrian Zapletal. The Master’s student and his fellow student Dimitri Höhler have substantially contributed to the development of SoftWipe. To select assessment criteria, they relied on existing standards that are used in safety-critical environments, such as at NASA or CERN.

“Our research revealed enormous discrepancies in software quality,” says co-author Professor Carsten Sinz of ITI. Many programs, such as covid-sim, which is used in the UK for mathematical modeling of the COVID-19 disease, had a very low quality score and thus performed poorly in the ranking. The researchers recommend using programs such as SoftWipe by default in the selection and review process of software for scientific purposes.

How Does SoftWipe Work?

SoftWipe is a pipeline written in the Python3 programming language that uses several available static and dynamic code analyzers (most of them are freely available) in order to assess the code quality of software written in C/C++. In this process, SoftWipe compiles the software and then executes it so that programming errors can be detected during execution. Based on the output of the code analysis tools used, SoftWipe calculates a quality score between 0 (poor) and 10 (excellent) to compute an overall final score .

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Materials provided by Karlsruher Institut für Technologie (KIT). Note: Content may be edited for style and length.

And even though we know that this fast expansion created particles, atoms, stars, galaxies and life as we know it today, the details of how it all happened are still unknown.

Now a new study performed by researchers from University of Copenhagen reveals insights on how it all began.

“We have studied a substance called Quark-Gluon Plasma that was the only matter, which existed during the first microsecond of Big Bang. Our results tell us a unique story of how the plasma evolved in the early stage of the universe,” explains You Zhou, Associate Professor at the Niels Bohr Institute, University of Copenhagen.

“First the plasma that consisted of quarks and gluons was separated by the hot expansion of the universe. Then the pieces of quark reformed into so-called hadrons. A hadron with three quarks makes a proton, which is part of atomic cores. These cores are the building blocks that constitutes earth, ourselves and the universe that surrounds us,” he adds.

From fluent and smooth to the strong building blocks of life

The Quark-Gluon Plasma (QGP) was present in the first 0.000001 second of Big Bang and thereafter it disappeared because of the expansion.

But by using the Large Hadron Collider at CERN, researchers were able to recreate this first matter in history and trace back what happened to it.

“The collider smashes together ions from the plasma with great velocity — almost like the speed of light. This makes us able to see how the QGP evolved from being its own matter to the cores in atoms and the building blocks of life,” says You Zhou.

“In addition to using the Large Hadron Collider, the researches also developed an algorithm that is able to analyze the collective expansion of more produced particles at once, than ever possible before. Their results show that the QGP used to be a fluent liquid form and that it distinguishes itself from other matters by constantly changing its shape over time.

“For a long time researchers thought that the plasma was a form of gas, but our analysis confirm the latest milestone measurement, where the Hadron Collider showed that QGP was fluent and had a smooth soft texture like water. The new details we provide is that the plasma has changed its shape over time, which is quite surprising and different from any other matter we know and what we would have expected,” says You Zhou.

One step closer to the truth about Big Bang

Even though this might seem like a small detail, it brings us one step closer to solving the puzzle of the Big Bang and how the universe developed in the first microsecond, he elaborates.

“Every discovery is a brick that improves our chances of finding out the truth about Big Bang. It has taken us about 20 years to find out that the Quark-Gluon Plasma was fluent before it changed into hadrons and the building blocks of life. Therefore our new knowledge on the ever changing behavior of the plasma, is a major breakthrough for us,” You Zhou concludes.

The study has just been published in the journal Physics Letters B and is performed by You Zhou together with Zuzana Moravcova, who is a PhD at the Niels Bohr Institute at University of Copenhagen.