Ydin-kuori -nanopartikkelien valmistaminen laserablaatiolla nesteseoksessa

Tiivistelmä. Nanopartikkelien monet käyttömahdollisuudet eri tieteenaloilla tekevät niiden valmistamisesta mielenkiintoisen ja tärkeän tutkimuskohteen. Erityisesti ydin-kuori -rakenteiset nanopartikkelit tuovat uusia mahdollisuuksia. Laserablaatio nesteseoksessa eli LASiS on nopea, helppo ja ympäristöystävällinen tapa tuottaa nanopartikkeleita nesteeseen, joka tarjoaa pitkäikäisen säilytysmahdollisuuden partikkeleille. Tutkielmassani esittelen laserablaation nesteseoksessa, käyn läpi käytettävän laitteiston ja sen parmetrit sekä esittelen ablaatioprosessin. Etsin ja tuon yhteen tutkimustuloksia ydin-kuori rakenteisten nanopartikkelien valmistamisesta LASiS-menetelmällä. Käyn läpi tutkimuksien tuloksia ja vertailen niitä etsien yhtäläisyyksiä sekä eroavaisuuksia. Tavoitteenani on löytää yhteisiä ilmiöitä, jotka toisivat mahdollisuuksia uudenlaisten nanopartikkelien tuottamiselle sekä ilmiöiden lisätutkimuksille

Quantum Mechanics on SO(3) via Non-commutative Dual Variables

We formulate quantum mechanics on SO(3) using a non-commutative dual space representation for the quantum states, inspired by recent work in quantum gravity. The new non-commutative variables have a clear connection to the corresponding classical variables, and our analysis confirms them as the natural phase space variables, both mathematically and physically. In particular, we derive the first order (Hamiltonian) path integral in terms of the non-commutative variables, as a formulation of the transition amplitudes alternative to that based on harmonic analysis. We find that the non-trivial phase space structure gives naturally rise to quantum corrections to the action for which we find a closed expression. We then study both the semi-classical approximation of the first order path integral and the example of a free particle on SO(3). On the basis of these results, we comment on the relevance of similar structures and methods for more complicated theories with group-based configuration spaces, such as Loop Quantum Gravity and Spin Foam models.Comment: 29 pages; matches the published version plus footnote 7, a journal reference include

Flexible players within the sheaths:the intrinsically disordered proteins of myelin in health and disease

Abstract Myelin ensheathes selected axonal segments within the nervous system, resulting primarily in nerve impulse acceleration, as well as mechanical and trophic support for neurons. In the central and peripheral nervous systems, various proteins that contribute to the formation and stability of myelin are present, which also harbor pathophysiological roles in myelin disease. Many myelin proteins have common attributes, including small size, hydrophobic segments, multifunctionality, longevity, and regions of intrinsic disorder. With recent advances in protein biophysical characterization and bioinformatics, it has become evident that intrinsically disordered proteins (IDPs) are abundant in myelin, and their flexible nature enables multifunctionality. Here, we review known myelin IDPs, their conservation, molecular characteristics and functions, and their disease relevance, along with open questions and speculations. We place emphasis on classifying the molecular details of IDPs in myelin, and we correlate these with their various functions, including susceptibility to post-translational modifications, function in protein–protein and protein–membrane interactions, as well as their role as extended entropic chains. We discuss how myelin pathology can relate to IDPs and which molecular factors are potentially involved

Stability and flexibility of full-length human oligodendrocytic QKI6

Abstract Objective: Oligodendrocytes account for myelination in the central nervous system. During myelin compaction, key proteins are translated in the vicinity of the myelin membrane, requiring targeted mRNA transport. Quaking isoform 6 (QKI6) is a STAR domain-containing RNA transport protein, which binds a conserved motif in the 3′-UTR of certain mRNAs, affecting the translation of myelination-involved proteins. RNA binding has been earlier structurally characterized, but information about full-length QKI6 conformation is lacking. Based on known domains and structure predicitons, we expected full-length QKI6 to be flexible and carry disordered regions. Hence, we carried out biophysical and structural characterization of human QKI6. Results: We expressed and purified full-length QKI6 and characterized it using mass spectrometry, light scattering, small-angle X-ray scattering, and circular dichroism spectroscopy. QKI6 was monodisperse, folded, and mostly dimeric, being oxidation-sensitive. The C-terminal tail was intrinsically disordered, as predicted. In the absence of RNA, the RNA-binding subdomain is likely to present major flexibility. In thermal stability assays, a double sequential unfolding behaviour was observed in the presence of phosphate, which may interact with the RNA-binding domain. The results confirm the flexibility and partial disorder of QKI6, which may be functionally relevant

How does protein zero assemble compact myelin?

Abstract Myelin protein zero (P0), a type I transmembrane protein, is the most abundant protein in peripheral nervous system (PNS) myelin—the lipid-rich, periodic structure of membrane pairs that concentrically encloses long axonal segments. Schwann cells, the myelinating glia of the PNS, express P0 throughout their development until the formation of mature myelin. In the intramyelinic compartment, the immunoglobulin-like domain of P0 bridges apposing membranes via homophilic adhesion, forming, as revealed by electron microscopy, the electron-dense, double “intraperiod line” that is split by a narrow, electron-lucent space corresponding to the extracellular space between membrane pairs. The C-terminal tail of P0 adheres apposing membranes together in the narrow cytoplasmic compartment of compact myelin, much like myelin basic protein (MBP). In mouse models, the absence of P0, unlike that of MBP or P2, severely disturbs myelination. Therefore, P0 is the executive molecule of PNS myelin maturation. How and when P0 is trafficked and modified to enable myelin compaction, and how mutations that give rise to incurable peripheral neuropathies alter the function of P0, are currently open questions. The potential mechanisms of P0 function in myelination are discussed, providing a foundation for the understanding of mature myelin development and how it derails in peripheral neuropathies

The intrinsically disordered protein glue of the myelin major dense line:linking AlphaFold2 predictions to experimental data

Abstract Numerous human proteins are classified as intrinsically disordered proteins (IDPs). Due to their physicochemical properties, high-resolution structural information about IDPs is generally lacking. On the other hand, IDPs are known to adopt local ordered structures upon interactions with e.g. other proteins or lipid membrane surfaces. While recent developments in protein structure prediction have been revolutionary, their impact on IDP research at high resolution remains limited. We took a specific example of two myelin-specific IDPs, the myelin basic protein (MBP) and the cytoplasmic domain of myelin protein zero (P0ct). Both of these IDPs are crucial for normal nervous system development and function, and while they are disordered in solution, upon membrane binding, they partially fold into helices, being embedded into the lipid membrane. We carried out AlphaFold2 predictions of both proteins and analysed the models in light of experimental data related to protein structure and molecular interactions. We observe that the predicted models have helical segments that closely correspond to the membrane-binding sites on both proteins. We furthermore analyse the fits of the models to synchrotron-based X-ray scattering and circular dichroism data from the same IDPs. The models are likely to represent the membrane-bound state of both MBP and P0ct, rather than the conformation in solution. Artificial intelligence-based models of IDPs appear to provide information on the ligand-bound state of these proteins, instead of the conformers dominating free in solution. We further discuss the implications of the predictions for mammalian nervous system myelination and their relevance to understanding disease aspects of these IDPs