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  • DNA shape and packing manipulation: groundbreaking method

    DNA shape and packing manipulation: groundbreaking method

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    Newswise — A human cell harbors roughly 2 meters of DNA, encompassing the essential genetic information of an individual. If one were to unwind and stretch out all the DNA contained within a single person, it would span a staggering distance – enough to reach the sun and back 60 times over. In order to manage such an astounding volume of biological information, the cell compacts its DNA into tightly packed chromosomes.

    “Imagine DNA as a piece of paper upon which all our genetic information is written.” Says Minke A.D. Nijenhuis, co-corresponding author. “The paper is folded into a very tight structure in order to fit all of that information into a small cell nucleus. To read the information, however, parts of the paper have to be unfolded and then refolded. This spatial organization of our genetic code is a central mechanism of life. We therefore wanted to create a methodology that allows researchers to engineer and study the compaction of double-stranded DNA.”

    Triple helical structure provides protection and compactness

    Natural DNA is often double-stranded: one strand to encode the genes and one backup strand, intertwined in a double helix. The double helix is stabilized by Watson-Crick interactions, which allow the two strands to recognize and pair with one another. Yet there exists another, lesser-known class of interactions between DNA. These so-called normal or reverse Hoogsteen interactions allow a third strand to join in, forming a beautiful triple helix (Figure 2).

    In a recent paper, published in Advanced Materials, researchers from the Gothelf lab debut a general method to organize double-stranded DNA, based on Hoogsteen interactions. The study unambiguously demonstrates that triplex-forming strands are capable of sharply bending or “folding” double-stranded DNA to create compacted structures. The appearance of these structures range from hollow two-dimensional shapes to dense 3D constructs and everything in-between, including a structure resembling a potted flower. Gothelf and co-workers have named their method triplex origami (Figure 3).

    With triplex origami, scientists can achieve a level of artificial control over the shape of double-stranded DNA that was previously unimaginable, thereby opening new avenues of exploration. It has recently been suggested that triplex formation plays a role in the natural compaction of genetic DNA and the current study may offer insight into this fundamental biological process.

    Potential in gene therapy and beyond

    The work also demonstrates that the Hoogsteen-mediated triplex formation shields the DNA against enzymatic degradation. Hence, the ability to compact and protect DNA with the triplex origami method may have large implications for gene therapy, wherein diseased cells are repaired by encoding a function that they are missing into a deliverable piece of double-stranded DNA.

    This biological marvel of DNA sequence and structure has also been applied in nanoscale materials engineering, yielding applications in therapeutics, diagnostics, and many other areas. “For the past four decades, DNA nanotechnology has almost exclusively relied on Watson-Crick base interactions to pair up single DNA strands and organize them into custom nanostructures.” Says Professor Kurt V. Gothelf. “We now know that Hoogsteen interactions have the same potential to organize double-stranded DNA, which presents a significant conceptual expansion for the field.”

    Gothelf and co-workers demonstrated that Hoogsteen-mediated folding is compatible with state-of-the-art Watson-Crick-based methods. Due to comparative rigidity of double-stranded DNA, however, triplex origami structures require fewer starting materials. This allows larger structures to be formed at significantly lower cost.

    The new method has the limitation that triplex formation typically requires long stretches of purine bases within the double-stranded DNA and the researchers have therefore used artificial DNA sequences, instead of natural genetic DNA. However, in the future they will work towards overcoming this limitation.

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  • Improvisation and creativity in professional jazz musicians

    Improvisation and creativity in professional jazz musicians

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    Newswise — World-renowned jazz musicians are often praised for their creative ingenuity. But how do they make up improvisations? And what makes artists’ solos  more enticing than those of less skilled players? These questions continue to puzzle not only jazz aficionados, but also psychological researchers. Two leading theories have dominated so far: Either musicians learn to master rules telling them what they can and cannot play – a sort of “secret language of jazz.” Or, each musician builds up a personal library of melodic patterns – “licks” – that they can draw upon and recombine in new and interesting ways. Over the years, musical scholars have collected many such volumes of “licks” for learners to practice. Yet, the fact that a certain combination of notes recurs many times is no proof of an underlying movement pattern stored in the brains of musicians—it could just be a sheer coincidence.

    The ‘library theory’ of jazz improvisation
    A new scientific study, just published in the journal Cognition, provides the first solid psychological evidence for the library theory of jazz improvisation. For the first time ever, researchers from Aarhus University and Georgia State University found that expert jazz musicians play certain note combinations with much more consistent timing and force than others. Regardless if these “licks” were played fast or slow, loud or soft, the relative rhythms and accents remained very similar. This strongly suggests that each player possesses a collection of patterns that are directly grounded in their own body and brain. Many jazz experts have called it their personal “vocabulary.” Interestingly, the new study found that these improvisation vocabularies vary between different players.

    Martin Norgaard, born and raised in Denmark, now Associate Professor of Music Education at Geogia State University in Atlanta comments further: “It is fascinating that expert jazz musicians store linked audio and motor representations in the brain – that is both the sound of licks and information about how to play them. As a jazz violinist myself, I often hear licks I want to play while improvising but the motor representation is not complete so the lick doesn’t come out right. Based on our research, that should happen less as expertise develops.”

    Stylistically appropriate and novel – hallmarks of creativity
    Using an advanced computer model, the researchers furthermore showed that “licks” tend to occur in relatively predictable contexts but simultaneously evoke greater surprise and uncertainty in the listener. This finding fits well with leading theories in psychology and neuroscience about human creativity and what makes certain types of music particularly enjoyable to listen to. Specifically, melodies in the personal vocabularies of jazz improvisers are typically both stylistically appropriate and novel—the two hallmarks of creativity according to scientists.

    “The fact that the solos of jazz experts evoke strong expectations in listeners and simultaneously surprise them might be exactly what makes these melodies so catchy and memorable. This may ultimately help us understand why some musicians become famous while others don’t,” said senior author Niels Chr. Hansen, Assistant Professor at Aarhus Institute of Advanced Studies at Aarhus University, Denmark.

    The research results – how did they do it?

    • The researchers analysed nearly 100,000 notes played on a MIDI keyboard by the artist-level jazz pianist Kevin Bales, during 11 live music gigs for audiences in the United States. This collection of solos was compared to recordings of 25 experienced jazz pianists taking part in a previous laboratory experiment.
    • For each recurring 5-note sequence, the durations of notes and the force with which they were played were compared across versions of the same pattern to find the set of licks that were played the most consistently across different tempi and loudness.
    • A computational model was trained on the Weimar Jazz Database consisting of more than 200,000 notes from 456 improvised songs by various jazz artists to estimate how much surprise and uncertainty each note in Kevin Bales’ improvised solos would evoke in an average jazz listener.

    Where can I find the scientific article?

    • Download: Until 18 December 2022, the article can be accessed freely via this link: https://authors.elsevier.com/c/1f-OF2Hx2pj8N
    • Citation: Norgaard, M., Bales, K., & Hansen, N.C. (2023). Linked auditory and motor patterns in the improvisation vocabulary of an artist-level jazz pianist. Cognition, 230. doi:10.1016/j.cognition.2022.105308

    Funding

    The study has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 754513 and The Aarhus University Research Foundation. 

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