On-line (HPLC-NMR) and off-line phytochemical profiling of the Australian plant, Lasiopetalum macrophyllum

On-line (HPLC-NMR) and off-line (HPLC, NMR and MS) methodologies were used to profile the constituents present in the crude extract of Lasiopetalum macrophyllum. On-flow and stop-flow HPLC-NMR supported the presence of trans-tiliroside and permitted partial identification of cis-tiliroside and 4'-methoxy-trans-tiliroside. Off-line isolation led to the unequivocal identification of four flavanoid glycosides including a new structural derivative, 4'-methoxy-cis-tiliroside. This is the first report of flavonoid glycosides occurring in this plant genus. In addition, a number of structure revisions have been proposed for previously reported flavonoid glycosides that were incorrectly assigned

Muscular diacylglycerol metabolism and insulin resistance

Failure of insulin to elicit an increase in glucose uptake and metabolism in target tissues such as skeletal muscle is a major characteristic of non-insulin dependent type 2 diabetes mellitus. A strong correlation between intramyocellular triacylglycerol concentrations and the severity of insulin resistance has been found and led to the assumption that lipid oversupply to skeletal muscle contributes to reduced insulin action. However, the molecular mechanism that links intramyocellular lipid content with the generation of muscle insulin resistance is still unclear. It appears unlikely that the neutral lipid metabolite triacylglycerol directly impairs insulin action. Hence it is believed that intermediates in fatty acid metabolism, such as fatty acyl-CoA, ceramides or diacylglycerol (DAG) link fat deposition in the muscle to compromised insulin signaling. DAG is identified as a potential mediator of lipid-induced insulin resistance, as increased DAG levels are associated with protein kinase C activation and a reduction in both insulin-stimulated IRS-1 tyrosine phosphorylation and PI3 kinase activity. As DAG is an intermediate in the synthesis of triacylglycerol from fatty acids and glycerol, its level can be lowered by either improving the oxidation of cellular fatty acids or by accelerating the incorporation of fatty acids into triacylglycerol. This review discusses the evidence that implicates DAG being central in the development of muscular insulin resistance. Furthermore, we will discuss if and how modulation of skeletal muscle DAG levels could function as a possible therapeutic target for the treatment of type 2 diabetes mellitus

Dynamic control of selectivity in the ubiquitination pathway revealed by an ASP to GLU substitution in an intra-molecular salt-bridge network

Ubiquitination relies on a subtle balance between selectivity and promiscuity achieved through specific interactions between ubiquitin-conjugating enzymes (E2s) and ubiquitin ligases (E3s). Here, we report how a single aspartic to glutamic acid substitution acts as a dynamic switch to tip the selectivity balance of human E2s for interaction toward E3 RING-finger domains. By combining molecular dynamic simulations, experimental yeast-two-hybrid screen of E2-E3 (RING) interactions and mutagenesis, we reveal how the dynamics of an internal salt-bridge network at the rim of the E2-E3 interaction surface controls the balance between an “open”, binding competent, and a “closed”, binding incompetent state. The molecular dynamic simulations shed light on the fine mechanism of this molecular switch and allowed us to identify its components, namely an aspartate/glutamate pair, a lysine acting as the central switch and a remote aspartate. Perturbations of single residues in this network, both inside and outside the interaction surface, are sufficient to switch the global E2 interaction selectivity as demonstrated experimentally. Taken together, our results indicate a new mechanism to control E2-E3 interaction selectivity at an atomic level, highlighting how minimal changes in amino acid side-chain affecting the dynamics of intramolecular salt-bridges can be crucial for protein-protein interactions. These findings indicate that the widely accepted sequence-structure-function paradigm should be extended to sequence-structure-dynamics-function relationship and open new possibilities for control and fine-tuning of protein interaction selectivity

Disentangling conical intersection and coherent molecular dynamics in methyl bromide with attosecond transient absorption spectroscopy

Attosecond probing of core-level electronic transitions provides a sensitive tool for studying valence molecular dynamics with atomic, state, and charge specificity. In this report, we employ attosecond transient absorption spectroscopy to follow the valence dynamics of strong-field initiated processes in methyl bromide. By probing the 3d core-to-valence transition, we resolve the strong field excitation and ensuing fragmentation of the neutral σ* excited states of methyl bromide. The results provide a clear signature of the non-adiabatic passage of the excited state wavepacket through a conical intersection. We additionally observe competing, strong field initiated processes arising in both the ground state and ionized molecule corresponding to vibrational and spin-orbit motion, respectively. The demonstrated ability to resolve simultaneous dynamics with few-femtosecond resolution presents a clear path forward in the implementation of attosecond XUV spectroscopy as a general tool for probing competing and complex molecular phenomena with unmatched temporal resolution

Psychological perspectives on musical experiences and skills: research in the Western Balkans and Western Europe

Psychology of Music is a flourishing area of research in the Western Balkans. However, much of its findings and insights have remained relatively unknown outside the region. Psychological Perspectives on Musical Experiences and Skills features recent research from the Western Balkans, foregrounding its specific topics, methods, and influences, and bringing it into productive conversation with complementary research from Western Europe and further afield. The essays in this collection investigate the psychology of listening and performance and their relevance to music practice. Employing a range of research methodologies, they address divergent themes, from a cross-cultural understanding of aesthetic experiences and innovations to attract new audiences, to developmental perspectives on musical growth and the challenges of mastering performance skills. Authors reflect independently and collaboratively on how these psychological processes are shaped by the different traditions and geopolitical conditions inside and outside the Western Balkans. The result is a volume that emphasizes how musical experiences and practices happen not in isolation but in socio-cultural environments that contribute to their definition. This work will appeal to musicians, music educators, students, researchers, and psychologists with an interest in the psychology of music and exemplify ways forward in decolonizing academia

Introduction: Music psychology research in the Western Balkans and Western Europe

The psychology of music is a broad research area in the range of questions and topics it addresses and the interdisciplinary research methods it employs to investigate music perception, cognition, emotion, and performance in every day and expert musical situations. It is an area of research flourishing in the Western Balkans as well as in Western Europe. This introductory chapter provides a brief historical overview of research in the Western Balkans, which has received relatively less attention and coverage in international research publications. It presents developments in music psychology in countries of former Yugoslavia-Bosnia and Herzegovina, Croatia, Montenegro, North Macedonia, Serbia, and Slovenia. Next, a preview of the book is offered that is a compilation of research originated in the Western Balkans and Western Europe on key themes of the psychology of music: Aesthetic emotional responses to music, listening to music in various contexts, music cognition and skill development, and then, the role of motivation, personality and environmental scaffolding for musical development, followed by professional challenges and well-being of musicians. Whilst the main contribution is to develop knowledge and understanding of music psychology, a secondary contribution is to raise awareness of research in this subject area as conducted for over 40 years in the Western Balkans and promote dialogue between research conducted across Europe and hopefully beyond

Conclusion: Progressing the state of the art of music psychology

Research from Western Europe tends to be better known and more frequently published than research from the Western Balkans. Various factors contribute to such imbalances of publication and recognition, including socio-economic, political, linguistic, and psychological, in the case of implicit biases. This book demonstrates the rich history of research in the psychology of music in the Western Balkans and aims to address power imbalances by explicitly promoting research from this region. In this concluding chapter, we argue for the opportunities offered by collaborative, interdisciplinary research to enable a more inclusive discipline of the psychology of music, with greater equality of contributions and embracing the diversity of knowledge and understanding. We reflect on the overlaps and differences between the research captured in this book, which originated in Western Europe and the Western Balkans. Whilst similarities and overlaps are most prevalent, subtle differences are also apparent in specific specialisms in knowledge development. Furthermore, contexts such as variations in systems and practices of music education and variations in musical preferences demonstrate the need for research to be situated rather than being assumed to be context-independent. This offers a tension for researchers to add to generalisable knowledge or develop context-dependent insights. Such tensions need to be first of all acknowledged in mainstream music psychology, highlighting the limitations of published research, and opening a larger platform for research from a diversity of regions, and cultural and research practices