@article{18481,
  abstract     = {A tight regulation of morphogen production is key for morphogen gradient formation and thereby for reproducible and organised organ development. Although many genetic interactions involved in the establishment of morphogen production domains are known, the biophysical mechanisms of morphogen source formation are poorly understood. Here we addressed this by focusing on the morphogen Sonic hedgehog (Shh) in the vertebrate neural tube. Shh is produced by the adjacently located notochord and by the floor plate of the neural tube. Using a data-constrained computational screen, we identified different possible mechanisms by which floor plate formation can occur, only one of which is consistent with experimental data. In this mechanism, the floor plate is established rapidly in response to Shh from the notochord and the dynamics of regulatory interactions within the neural tube. In this process, uniform activators and Shh-dependent repressors are key for establishing the floor plate size. Subsequently, the floor plate becomes insensitive to Shh and increases in size due to tissue growth, leading to scaling of the floor plate with neural tube size. In turn, this results in scaling of the Shh amplitude with tissue growth. Thus, this mechanism ensures a separation of time scales in floor plate formation, so that the floor plate domain becomes growth-dependent after an initial rapid establishment phase. Our study raises the possibility that the time scale separation between specification and growth might be a common strategy for scaling the morphogen gradient amplitude in growing organs. The model that we developed provides a new opportunity for quantitative studies of morphogen source formation in growing tissues.},
  author       = {Ho, Richard D.J.G. and Kishi, Kasumi and Majka, Maciej and Kicheva, Anna and Zagórski, Marcin P},
  issn         = {1553-7358},
  journal      = {PLoS Computational Biology},
  publisher    = {Public Library of Science},
  title        = {{Dynamics of morphogen source formation in a growing tissue}},
  doi          = {10.1371/journal.pcbi.1012508},
  volume       = {20},
  year         = {2024},
}

@article{18554,
  abstract     = {We prove the Eigenstate Thermalization Hypothesis for general Wigner-type matrices in the bulk of the self-consistent spectrum, with optimal control on the fluctuations for obs ervables of arbitrary rank. As the main technical ingredient, we prove rank-uniform optimal local laws for one and two resolvents of a Wigner-type matrix with regular observables. Our results hold under very general conditions on the variance profile, even allowing many vanishing entries, demonstrating that Eigenstate Thermalization occurs robustly across a diverse class of random matrix ensembles, for which the underlying quantum system has a non-trivial spatial structure.},
  author       = {Erdös, László and Riabov, Volodymyr},
  issn         = {1432-0916},
  journal      = {Communications in Mathematical Physics},
  number       = {12},
  publisher    = {Springer Nature},
  title        = {{Eigenstate Thermalization Hypothesis for Wigner-type matrices}},
  doi          = {10.1007/s00220-024-05143-y},
  volume       = {405},
  year         = {2024},
}

@article{13975,
  abstract     = {We consider the spectrum of random Laplacian matrices of the form Ln=An−Dn where An
 is a real symmetric random matrix and Dn is a diagonal matrix whose entries are equal to the corresponding row sums of An. If An is a Wigner matrix with entries in the domain of attraction of a Gaussian distribution, the empirical spectral measure of Ln is known to converge to the free convolution of a semicircle distribution and a standard real Gaussian distribution. We consider real symmetric random matrices An with independent entries (up to symmetry) whose row sums converge to a purely non-Gaussian infinitely divisible distribution, which fall into the class of Lévy–Khintchine random matrices first introduced by Jung [Trans Am Math Soc, 370, (2018)]. Our main result shows that the empirical spectral measure of Ln  converges almost surely to a deterministic limit. A key step in the proof is to use the purely non-Gaussian nature of the row sums to build a random operator to which Ln converges in an appropriate sense. This operator leads to a recursive distributional equation uniquely describing the Stieltjes transform of the limiting empirical spectral measure.},
  author       = {Campbell, Andrew J and O’Rourke, Sean},
  issn         = {1572-9230},
  journal      = {Journal of Theoretical Probability},
  pages        = {933--973},
  publisher    = {Springer Nature},
  title        = {{Spectrum of Lévy–Khintchine random laplacian matrices}},
  doi          = {10.1007/s10959-023-01275-4},
  volume       = {37},
  year         = {2024},
}

@article{17281,
  abstract     = {We extend the free convolution of Brown measures of R-diagonal elements introduced by Kösters and Tikhomirov [ 28] to fractional powers. We then show how this fractional free convolution arises naturally when studying the roots of random polynomials with independent coefficients under repeated differentiation. When the proportion of derivatives to the degree approaches one, we establish central limit theorem-type behavior and discuss stable distributions.},
  author       = {Campbell, Andrew J and O'Rourke, Sean and Renfrew, David T},
  issn         = {1687-0247},
  journal      = {International Mathematics Research Notices},
  number       = {13},
  pages        = {10189--10218},
  publisher    = {Oxford University Press},
  title        = {{The fractional free convolution of R-diagonal elements and random polynomials under repeated differentiation}},
  doi          = {10.1093/imrn/rnae062},
  volume       = {2024},
  year         = {2024},
}

@article{14408,
  abstract     = {We prove that the mesoscopic linear statistics ∑if(na(σi−z0)) of the eigenvalues {σi}i of large n×n non-Hermitian random matrices with complex centred i.i.d. entries are asymptotically Gaussian for any H20-functions f around any point z0 in the bulk of the spectrum on any mesoscopic scale 0<a<1/2. This extends our previous result (Cipolloni et al. in Commun Pure Appl Math, 2019. arXiv:1912.04100), that was valid on the macroscopic scale, a=0
, to cover the entire mesoscopic regime. The main novelty is a local law for the product of resolvents for the Hermitization of X at spectral parameters z1,z2 with an improved error term in the entire mesoscopic regime |z1−z2|≫n−1/2. The proof is dynamical; it relies on a recursive tandem of the characteristic flow method and the Green function comparison idea combined with a separation of the unstable mode of the underlying stability operator.},
  author       = {Cipolloni, Giorgio and Erdös, László and Schröder, Dominik J},
  issn         = {1432-2064},
  journal      = {Probability Theory and Related Fields},
  pages        = {1131--1182},
  publisher    = {Springer Nature},
  title        = {{Mesoscopic central limit theorem for non-Hermitian random matrices}},
  doi          = {10.1007/s00440-023-01229-1},
  volume       = {188},
  year         = {2024},
}

@article{17375,
  abstract     = {We consider the spectral radius of a large random matrix X with independent, identically distributed entries. We show that its typical size is given by a precise three-term asymptotics with an optimal error term beyond the radius of the celebrated circular law. The coefficients in this asymptotics are universal but they differ from a similar asymptotics recently proved for the rightmost eigenvalue of X in Cipolloni et al., Ann. Probab. 51(6), 2192–2242 (2023). To access the more complicated spectral radius, we need to establish a new decorrelation mechanism for the low-lying singular values of X − z for different complex shift parameters z using the Dyson Brownian Motion.},
  author       = {Cipolloni, Giorgio and Erdös, László and Xu, Yuanyuan},
  issn         = {0022-2488},
  journal      = {Journal of Mathematical Physics},
  number       = {6},
  publisher    = {AIP Publishing},
  title        = {{Precise asymptotics for the spectral radius of a large random matrix}},
  doi          = {10.1063/5.0209705},
  volume       = {65},
  year         = {2024},
}

@article{15025,
  abstract     = {We consider quadratic forms of deterministic matrices A evaluated at the random eigenvectors of a large N×N GOE or GUE matrix, or equivalently evaluated at the columns of a Haar-orthogonal or Haar-unitary random matrix. We prove that, as long as the deterministic matrix has rank much smaller than √N, the distributions of the extrema of these quadratic forms are asymptotically the same as if the eigenvectors were independent Gaussians. This reduces the problem to Gaussian computations, which we carry out in several cases to illustrate our result, finding Gumbel or Weibull limiting distributions depending on the signature of A. Our result also naturally applies to the eigenvectors of any invariant ensemble.},
  author       = {Erdös, László and McKenna, Benjamin},
  issn         = {1050-5164},
  journal      = {Annals of Applied Probability},
  number       = {1B},
  pages        = {1623--1662},
  publisher    = {Institute of Mathematical Statistics},
  title        = {{Extremal statistics of quadratic forms of GOE/GUE eigenvectors}},
  doi          = {10.1214/23-AAP2000},
  volume       = {34},
  year         = {2024},
}

@phdthesis{17164,
  abstract     = {This thesis is structured into two parts. In the first part, we consider the random
variable X := Tr(f1(W)A1 . . . fk(W)Ak) where W is an N × N Hermitian Wigner matrix, k ∈ N, and we choose (possibly N-dependent) regular functions f1, . . . , fk as well as
bounded deterministic matrices A1, . . . , Ak. In this context, we prove a functional central
limit theorem on macroscopic and mesoscopic scales, showing that the fluctuations of X
around its expectation are Gaussian and that the limiting covariance structure is given
by a deterministic recursion. We further give explicit error bounds in terms of the scaling
of f1, . . . , fk and the number of traceless matrices among A1, . . . , Ak, thus extending
the results of Cipolloni, Erdős and Schröder [40] to products of arbitrary length k ≥ 2.
Analyzing the underlying combinatorics leads to a non-recursive formula for the variance
of X as well as the covariance of X and Y := Tr(fk+1(W)Ak+1 . . . fk+ℓ(W)Ak+ℓ) of similar
build. When restricted to polynomials, these formulas reproduce recent results of Male,
Mingo, Peché, and Speicher [107], showing that the underlying combinatorics of noncrossing partitions and annular non-crossing permutations continue to stay valid beyond
the setting of second-order free probability theory. As an application, we consider the
fluctuation of Tr(eitW A1e
−itW A2)/N around its thermal value Tr(A1) Tr(A2)/N2 when t
is large and give an explicit formula for the variance.
The second part of the thesis collects three smaller projects focusing on different random
matrix models. In the first project, we show that a class of weakly perturbed Hamiltonians
of the form Hλ = H0 + λW, where W is a Wigner matrix, exhibits prethermalization.
That is, the time evolution generated by Hλ relaxes to its ultimate thermal state via an
intermediate prethermal state with a lifetime of order λ
−2
. As the main result, we obtain
a general relaxation formula, expressing the perturbed dynamics via the unperturbed
dynamics and the ultimate thermal state. The proof relies on a two-resolvent global law
for the deformed Wigner matrix Hλ.
The second project focuses on correlated random matrices, more precisely on a correlated N × N Hermitian random matrix with a polynomially decaying metric correlation
structure. A trivial a priori bound shows that the operator norm of this model is stochastically dominated by √
N. However, by calculating the trace of the moments of the matrix
and using the summable decay of the cumulants, the norm estimate can be improved to a
bound of order one.
In the third project, we consider a multiplicative perturbation of the form UA(t) where U
is a unitary random matrix and A = diag(t, 1, ..., 1). This so-called UA model was
first introduced by Fyodorov [73] for its applications in scattering theory. We give a
general description of the eigenvalue trajectories obtained by varying the parameter t and
introduce a flow of deterministic domains that separates the outlier resulting from the
rank-one perturbation from the typical eigenvalues for all sub-critical timescales. The
results are obtained under generic assumptions on U that hold for various unitary random
matrices, including the circular unitary ensemble (CUE) in the original formulation of
the model.},
  author       = {Reker, Jana},
  issn         = {2663-337X},
  keywords     = {Random Matrices, Spectrum, Central Limit Theorem, Resolvent, Free Probability},
  pages        = {206},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Central limit theorems for random matrices: From resolvents to free probability}},
  doi          = {10.15479/at:ista:17164},
  year         = {2024},
}

@article{17049,
  abstract     = {We consider large non-Hermitian NxN matrices with an additive independent, identically distributed (i.i.d.) noise for each matrix elements. We show that already a small noise of variance 1/N completely thermalises the bulk singular vectors, in particular they satisfy the strong form of Quantum Unique Ergodicity (QUE) with an optimal speed of convergence. In physics terms, we thus extend the Eigenstate Thermalisation Hypothesis, formulated originally by Deutsch [34] and proven for Wigner matrices in [23], to arbitrary non-Hermitian matrices with an i.i.d. noise. As a consequence we obtain an optimal lower bound on the diagonal overlaps of the corresponding non-Hermitian eigenvectors. This quantity, also known as the (square of the) eigenvalue condition number measuring the sensitivity of the eigenvalue to small perturbations, has notoriously escaped rigorous treatment beyond the explicitly computable Ginibre ensemble apart from the very recent upper bounds given in [7] and [45]. As a key tool, we develop a new systematic decomposition of general observables in random matrix theory that governs the size of products of resolvents with deterministic matrices in between.},
  author       = {Cipolloni, Giorgio and Erdös, László and Henheik, Sven Joscha and Schröder, Dominik J},
  issn         = {1096-0783},
  journal      = {Journal of Functional Analysis},
  number       = {4},
  publisher    = {Elsevier},
  title        = {{Optimal lower bound on eigenvector overlaps for non-Hermitian random matrices}},
  doi          = {10.1016/j.jfa.2024.110495},
  volume       = {287},
  year         = {2024},
}

@article{15378,
  abstract     = {We consider N×N non-Hermitian random matrices of the form X+A, where A is a general deterministic matrix and N−−√X consists of independent entries with zero mean, unit variance, and bounded densities. For this ensemble, we prove (i) a Wegner estimate, i.e. that the local density of eigenvalues is bounded by N1+o(1) and (ii) that the expected condition number of any bulk eigenvalue is bounded by N1+o(1); both results are optimal up to the factor No(1). The latter result complements the very recent matching lower bound obtained in [15] (arXiv:2301.03549) and improves the N-dependence of the upper bounds in [5,6,32] (arXiv:1906.11819, arXiv:2005.08930, arXiv:2005.08908). Our main ingredient, a near-optimal lower tail estimate for the small singular values of X+A−z, is of independent interest.},
  author       = {Erdös, László and Ji, Hong Chang},
  issn         = {1097-0312},
  journal      = {Communications on Pure and Applied Mathematics},
  number       = {9},
  pages        = {3785--3840},
  publisher    = {Wiley},
  title        = {{Wegner estimate and upper bound on the eigenvalue condition number of non-Hermitian random matrices}},
  doi          = {10.1002/cpa.22201},
  volume       = {77},
  year         = {2024},
}

@article{18762,
  abstract     = {Consider the random variable $\mathrm{Tr}( f_1(W)A_1\dots f_k(W)A_k)$ where $W$ is an $N\times N$ Hermitian Wigner matrix, $k\in\mathbb{N}$, and choose (possibly $N$-dependent) regular functions $f_1,\dots, f_k$ as well as bounded deterministic matrices $A_1,\dots,A_k$. We give a functional central limit theorem showing that the fluctuations around the expectation are Gaussian. Moreover, we determine the limiting covariance structure and give explicit error bounds in terms of the scaling of $f_1,\dots,f_k$ and the number of traceless matrices among $A_1,\dots,A_k$, thus extending the results of [Cipolloni, Erdős, Schröder 2023] to products of arbitrary length $k\geq2$. As an application, we consider the fluctuation of $\mathrm{Tr}(\mathrm{e}^{\mathrm{i} tW}A_1\mathrm{e}^{-\mathrm{i} tW}A_2)$ around its thermal value $\mathrm{Tr}(A_1)\mathrm{Tr}(A_2)$ when $t$ is large and give an explicit formula for the variance.},
  author       = {Reker, Jana},
  issn         = {1083-6489},
  journal      = {Electronic Journal of Probability},
  publisher    = {Institute of Mathematical Statistics},
  title        = {{Multi-point functional central limit theorem for Wigner matrices}},
  doi          = {10.1214/24-EJP1247},
  volume       = {29},
  year         = {2024},
}

@article{17154,
  abstract     = {We compute the deterministic approximation for mixed fluctuation moments of products of deterministic matrices and general Sobolev functions of Wigner matrices. Restricting to polynomials, our formulas reproduce recent results of Male et al. (Random Matrices Theory Appl. 11(2):2250015, 2022), showing that the underlying combinatorics of non-crossing partitions and annular non-crossing permutations continue to stay valid beyond the setting of second-order free probability theory. The formulas obtained further characterize the variance in the functional central limit theorem given in the recent companion paper (Reker in Preprint, arXiv:2204.03419, 2023). and thus allow identifying the fluctuation around the thermal value in certain thermalization problems.},
  author       = {Reker, Jana},
  issn         = {1572-9656},
  journal      = {Mathematical Physics, Analysis and Geometry},
  number       = {3},
  publisher    = {Springer Nature},
  title        = {{Fluctuation moments for regular functions of Wigner Matrices}},
  doi          = {10.1007/s11040-024-09483-y},
  volume       = {27},
  year         = {2024},
}

@article{18656,
  abstract     = {We consider the time evolution of the out-of-time-ordered correlator (OTOC) of two general observables 
 and 
 in a mean field chaotic quantum system described by a random Wigner matrix as its Hamiltonian. We rigorously identify three time regimes separated by the physically relevant scrambling and relaxation times. The main feature of our analysis is that we express the error terms in the optimal Schatten (tracial) norms of the observables, allowing us to track the exact dependence of the errors on their rank. In particular, for significantly overlapping observables with low rank the OTOC is shown to exhibit a significant local maximum at the scrambling time, a feature that may not have been noticed in the physics literature before. Our main tool is a novel multi-resolvent local law with Schatten norms that unifies and improves previous local laws involving either the much cruder operator norm (cf. [10]) or the Hilbert-Schmidt norm (cf. [11]).},
  author       = {Cipolloni, Giorgio and Erdös, László and Henheik, Sven Joscha},
  issn         = {1095-0753},
  journal      = {Advances in Theoretical and Mathematical Physics},
  number       = {6},
  pages        = {2025--2083},
  publisher    = {International Press of Boston},
  title        = {{Out-of-time-ordered correlators for Wigner matrices}},
  doi          = {10.4310/ATMP.241031013250},
  volume       = {28},
  year         = {2024},
}

@phdthesis{17319,
  abstract     = {This thesis comprises two distinct projects, each offering unique insights into fundamental
cellular processes. While distinct in their focus, these different perspectives have a common
theme: chemiosmotic theory and utilisation of the proton gradient for driving the essential
processes like auxin efflux and ATP synthesis, effectively bridging the membrane protein
structure and function from the realms of plant biology and cellular bioenergetics.
The first project of this thesis centres on the characterisation of PIN proteins, a class of
transmembrane transporters pivotal in the regulation of auxin transport and distribution in
plants. PINs form a conserved and phylogenetically abundant group of transporters present in
land plants and certain algae. Despite their great importance, they were one of the few elusive
proteins essential for plant development not to be structurally and mechanistically
characterised since their discovery almost 30 years ago. This work aimed to uncover the
structural and functional dynamics of the PIN protein-mediated auxin transport using an array
of experimental techniques, including protein purification, biochemical assays and structural
analysis. Through an exhaustive screening process that took several years and included testing
different PIN homologues, expression systems, constructs, and purification conditions, we
developed a robust protocol for isolating the pure, stable, and monodisperse PIN8 protein.
Moreover, utilising biophysical methods and buffer screening, we demonstrated that PIN8
exhibits detergent and pH-dependent stability, with mild detergents and lower pH (5.0 and 6.0)
being optimal for the stability of the protein. Using SEC-MALS and crosslinking, we
determined that PIN8 forms dimers, which was confirmed by our structural studies. We
obtained a cryo-EM map of PIN8 at pH 6.0, and, compared to recently published structures,
our map implies major pH-dependent conformational changes and possibly utilisation of the
proton gradient in the transport mechanism.
The subject of the second project was F1Fo-ATP synthase, an enzyme complex fundamental
to cellular energy metabolism. Through an approach integrating biochemical assays and
structural analysis, this research aimed to unveil the molecular mechanism of inhibition of ATP
synthase by yaku´amide, a bioactive compound with potential therapeutic implications. Using
submitochondrial particles and purified F1Fo-ATP synthase, we demonstrated that, contrary to
published data, yaku´amide inhibits both ATP hydrolysis and ATP synthesis reactions.
Moreover, we found that yaku´amide inhibitory activity is proton motive force (pmf)
dependent, with lower inhibition in a more coupled system. Utilising cryo-EM, we obtained
maps and models for the three main rotational states of murine ATP synthase (State 1 at 3.0 Å,
8
State 2 at 3.1 Å, and State 3 at 3.2 Å, overall). We observed several new features in our maps;
however, we cannot definitively determine the exact mechanism of yaku amide’s inhibition on
the protein due to either resolution limits or suboptimal binding of the inhibitor.},
  author       = {Lukic, Kristina},
  issn         = {2663-337X},
  pages        = {224},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Membrane proteins in plant physiology and bioenergetics : Investigating auxin efflux transporter PIN8 and ATP synthase inhibition by the novel inhibitor Yaku'amide B}},
  doi          = {10.15479/at:ista:17319},
  year         = {2024},
}

@article{17326,
  abstract     = {Magnetic fields in the stellar interiors are key candidates to explain observed core rotation rates inside solar-like stars along their evolution. Recently, asteroseismic estimates of radial magnetic field amplitudes near the hydrogen-burning shell (H-shell) inside about 24 red giants (RGs) have been obtained by measuring frequency splittings from their power spectra. Using general Lorentz-stress (magnetic) kernels, we investigated the potential for detectability of near-surface magnetism in a 1.3 M⊙ star of supersolar metallicity as it evolves from a mid subgiant to a late subgiant into an RG. Based on these sensitivity kernels, we decompose an RG into three zones—deep core, H-shell, and near-surface. The subgiants instead required decomposition into an inner core, an outer core, and a near-surface layer. Additionally, we find that for a low-frequency g-dominated dipolar mode in the presence of a typical stable magnetic field, ∼25% of the frequency shift comes from the H-shell and the remaining from deeper layers. The ratio of the subsurface tangential field to the radial field in the H-burning shell decides if subsurface fields may be potentially detectable. For p-dominated dipole modes close to vmax, this ratio is around two orders of magnitude smaller in subgiant phases than the corresponding RG. Further, with the availability of magnetic kernels, we propose lower limits of field strengths in crucial layers in our stellar model during its evolutionary phases. The theoretical prescription outlined here provides the first formal way to devise inverse problems for stellar magnetism and can be seamlessly employed for slow rotators.},
  author       = {Bhattacharya, Shatanik and Das, Srijan B and Bugnet, Lisa Annabelle and Panda, Subrata and Hanasoge, Shravan M.},
  issn         = {1538-4357},
  journal      = {Astrophysical Journal},
  number       = {1},
  publisher    = {IOP Publishing},
  title        = {{Detectability of axisymmetric magnetic fields from the core to the surface of oscillating post-main-sequence stars}},
  doi          = {10.3847/1538-4357/ad4708},
  volume       = {970},
  year         = {2024},
}

@article{18172,
  abstract     = {Red Giant stars host solar-like oscillations which have mixed character, being sensitive to conditions both in the outer convection zone and deep within the interior. The properties of these modes are sensitive to both core rotation and magnetic fields. While asteroseismic studies of the former have been done on a large scale, studies of the latter are currently limited to tens of stars. We aim to produce the first large catalogue of both magnetic and rotational perturbations. We jointly constrain these parameters by devising an automated method for fitting the power spectra directly. We successfully apply the method to 302 low-luminosity red giants. We find a clear bimodality in core rotation rate. The primary peak is at δνrot = 0.32 μHz, and the secondary at δνrot = 0.47 μHz. Combining our results with literature values, we find that the percentage of stars rotating much more rapidly than the population average increases with evolutionary state. We measure magnetic splittings of 2σ significance in 23 stars. While the most extreme magnetic splitting values appear in stars with masses > 1.1M⊙, implying they formerly hosted a convective core, a small but statistically significant magnetic splitting is measured at lower masses. Asymmetry between the frequencies of a rotationally split multiplet has previously been used to diagnose the presence of a magnetic perturbation. We find that of the stars with a significant detection of magnetic perturbation, 43\% do not show strong asymmetry. We find no strong evidence of correlation between the rotation and magnetic parameters.},
  author       = {Hatt, Emily J. and Ong, J. M.Joel and Nielsen, Martin B. and Chaplin, William J. and Davies, Guy R. and Deheuvels, Sébastien and Ballot, Jérôme and Li, Gang and Bugnet, Lisa Annabelle},
  issn         = {1365-2966},
  journal      = {Monthly Notices of the Royal Astronomical Society},
  number       = {2},
  pages        = {1060--1076},
  publisher    = {Oxford University Press},
  title        = {{Asteroseismic signatures of core magnetism and rotation in hundreds of low-luminosity red giants}},
  doi          = {10.1093/mnras/stae2053},
  volume       = {534},
  year         = {2024},
}

@article{15323,
  abstract     = {Supercomplexes of the respiratory chain are established constituents of the oxidative phosphorylation system, but their role in mammalian metabolism has been hotly debated. Although recent studies have shown that different tissues/organs are equipped with specific sets of supercomplexes, depending on their metabolic needs, the notion that supercomplexes have a role in the regulation of metabolism has been challenged. However, irrespective of the mechanistic conclusions, the composition of various high molecular weight supercomplexes remains uncertain. Here, using cryogenic electron microscopy, we demonstrate that mammalian (mouse) tissues contain three defined types of ‘respirasome’, supercomplexes made of CI, CIII2 and CIV. The stoichiometry and position of CIV differs in the three respirasomes, of which only one contains the supercomplex-associated factor SCAF1, whose involvement in respirasome formation has long been contended. Our structures confirm that the ‘canonical’ respirasome (the C-respirasome, CICIII2CIV) does not contain SCAF1, which is instead associated to a different respirasome (the CS-respirasome), containing a second copy of CIV. We also identify an alternative respirasome (A-respirasome), with CIV bound to the ‘back’ of CI, instead of the ‘toe’. This structural characterization of mouse mitochondrial supercomplexes allows us to hypothesize a mechanistic basis for their specific role in different metabolic conditions.},
  author       = {Vercellino, Irene and Sazanov, Leonid A},
  issn         = {1545-9985},
  journal      = {Nature Structural and Molecular Biology},
  pages        = {1061--1071},
  publisher    = {Springer Nature},
  title        = {{SCAF1 drives the compositional diversity of mammalian respirasomes}},
  doi          = {10.1038/s41594-024-01255-0},
  volume       = {31},
  year         = {2024},
}

@misc{18967,
  abstract     = {Background: We identified small molecule tricyclic pyrone compound CP2 as a mild mitochondrial complex I (MCI) inhibitor that induces neuroprotection in multiple mouse models of AD. One of the major concerns while targeting mitochondria is the production of reactive oxygen species (ROS). CP2 consists of two diastereoisomers, D1 and D2, with distinct activity and toxicity profiles. This study was designed to understand how structure of D1 and D2 affects their binding to MCI and the consequential impact on ROS production.

Method: The X-ray crystallography and cryo-electron microscopy (cryo-EM) at global resolution of 3.25-3.27Å were employed to identify the molecular structure of D1 and D2 and the D1 binding to the isolated ovine MCI. The assessment of the MCI inhibition and the extent of ROS generation were done in isolated MCI and human neuroblastoma MC65 cells using flow cytometry, a Seahorse extracellular flux analyzer, and the kinetic studies.

Result: In the closed conformation of MCI, D1 selectively binds to the deep Quinone-site (Qd) but not to the shallow Q-site (Qs), sharing the same binding pocket as rotenone. In the open MCI state, D1 exclusively binds to the Qs in contrast to rotenone, which binds Qd and Qs in both closed and open states. At the same concentrations, D1 inhibits respiration to a greater extent compared to D2 (5:1 ratio) and produces higher level of ROS.

Conclusion:Cryo-EM unambiguously identified binding of D1 to both the Qd and Qs sites, contingent upon the conformational state of MCI. In contrast to rotenone, D1 binds Qd only in the closed conformation during catalytic cycle, leading to mild inhibition. Superimposing X-ray crystallography data of D1 and D2 onto cryo-EM data suggests that the orientation of the methyl group in D2 induces a flatter conformation, resulting in lower binding affinity to MCI, which correlates with lower inhibition and toxicity compared to D1. At physiologically relevant concentrations, CP2 (D1:D2 = 1:1) demonstrates low MCI inhibition yielding negligible ROS levels. This observation provides new insight into the absence of toxicity associated with CP2 treatment in vivo, further highlighting feasibility for the development of safe and efficacious MCI inhibitors.},
  author       = {Petrova, Olga and Trushin, Sergey A and Nguyen, Thi Kim Oanh and Ostroot, Mark and Schellenberg, Matthew and Johnson, Graham and Trushina, Eugenia and Sazanov, Leonid A},
  booktitle    = {Alzheimer's & Dementia},
  issn         = {1552-5279},
  number       = {S6},
  publisher    = {Wiley},
  title        = {{Structure‐activity relationship study of neuroprotective complex I inhibitor CP2}},
  doi          = {10.1002/alz.085971},
  volume       = {20},
  year         = {2024},
}

@article{18581,
  abstract     = {Background: Human induced pluripotent stem cells represent a scalable source of youthful tissue progenitors and secretomes for regenerative therapies. The aim of our study was to investigate the potential of conditioned medium (CM) from hiPSC-mesenchymal progenitors (hiPSC-MPs) to stimulate osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (MSCs). We also investigated whether prolonged cultivation or osteogenic pre-differentiation of hiPSC-MPs could enhance the stimulatory activity of CM.
Methods: MSCs were isolated from 13 donors (age 20–90 years). CM derived from hiPSC-MPs was added to the MSC cultures and the effects on proliferation and osteogenic differentiation were examined after 14 days and 6 weeks. The stimulatory activity of hiPSC-MP-CM was compared with the activity of MSC-derived CM and with the activity of CM prepared from hiPSC-MPs pre-cultured in growth or osteogenic medium for 14 days. Comparative proteomic analysis of CM was performed to gain insight into the molecular components responsible for the stimulatory activity.
Results: Primary bone marrow-derived MSC exhibited variability, with a tendency towards lower proliferation and tri-lineage differentiation in older donors. hiPSC-MP-CM increased the proliferation and alkaline phosphatase activity of MSC from several adult/aged donors after 14 days of continuous supplementation under osteogenic conditions. However, CM supplementation failed to improve the mineralization of MSC pellets after 6 weeks under osteogenic conditions. hiPSC-MP-CM showed greater enhancement of proliferation and ALP activity than CM derived from bone marrow-derived MSCs. Moreover, 14-day cultivation but not osteogenic pre-differentiation of hiPSC-MPs strongly enhanced CM stimulatory activity. Quantitative proteomic analysis of d14-CM revealed a distinct profile of components that formed a highly interconnected associations network with two clusters, one functionally associated with binding and organization of actin/cytoskeletal components and the other with structural constituents of the extracellular matrix, collagen, and growth factor binding. Several hub proteins were identified that were reported to have functions in cell-extracellular matrix interaction, osteogenic differentiation and development.
Conclusions: Our data show that hiPSC-MP-CM enhances early osteogenic differentiation of human bone marrow-derived MSCs and that prolonged cultivation of hiPSC-MPs enhances CM-stimulatory activity. Proteomic analysis of the upregulated protein components provides the basis for further optimization of hiPSC-MP-CM for bone regenerative therapies.},
  author       = {Marolt Presen, Darja and Goeschl, Vanessa and Hanetseder, Dominik and Ogrin, Laura and Stetco, Alexandra Larissa and Tansek, Anja and Pozenel, Laura and Bruszel, Bella and Mitulovic, Goran and Oesterreicher, Johannes and Zipperle, Johannes and Schaedl, Barbara and Holnthoner, Wolfgang and Grillari, Johannes and Redl, Heinz},
  issn         = {1757-6512},
  journal      = {Stem Cell Research and Therapy},
  publisher    = {Springer Nature},
  title        = {{Prolonged cultivation enhances the stimulatory activity of hiPSC mesenchymal progenitor-derived conditioned medium}},
  doi          = {10.1186/s13287-024-03960-5},
  volume       = {15},
  year         = {2024},
}

@article{18904,
  abstract     = {The Planetary Transits and Oscillations of stars mission (PLATO) will allow us to measure surface rotation and monitor photometric activity of tens of thousands of main sequence solar-type and subgiant stars. This paper is the first of a series dedicated to the preparation of the analysis of stellar surface rotation and photospheric activity with the near-future PLATO data. We describe in this work the strategy that will be implemented in the PLATO pipeline to measure stellar surface rotation, photometric activity, and long-term modulations. The algorithms are applied on both noise-free and noisy simulations of solar-type stars, which include activity cycles, latitudinal differential rotation, and spot evolution. PLATO simulated systematics are included in the noisy light curves. We show that surface rotation periods can be recovered with confidence for most of the stars with only six months of observations and that the recovery rate of the analysis significantly improves as additional observations are collected. This means that the first PLATO data release will already provide a substantial set of measurements for this quantity, with a significant refinement on their quality as the instrument obtains longer light curves. Measuring the Schwabe-like magnetic activity cycle during the mission will require that the same field be observed over a significant timescale (more than four years). Nevertheless, PLATO will provide a vast and robust sample of solar-type stars with constraints on the activity-cycle length. Such a sample is lacking from previous missions dedicated to space photometry.},
  author       = {Breton, S. N. and Lanza, A. F. and Messina, S. and Pagano, I. and Bugnet, Lisa Annabelle and Corsaro, E. and García, R. A. and Mathur, S. and Santos, A. R. G. and Aigrain, S. and Amard, L. and Brun, A. S. and Degott, L. and Noraz, Q. and Palakkatharappil, D. B. and Panetier, E. and Strugarek, A. and Belkacem, K. and Goupil, M.-J and Ouazzani, R. M. and Philidet, J. and Renié, C. and Roth, O.},
  issn         = {1432-0746},
  journal      = {Astronomy & Astrophysics},
  publisher    = {EDP Sciences},
  title        = {{Measuring stellar surface rotation and activity with the PLATO mission. I. Strategy and application to simulated light curves}},
  doi          = {10.1051/0004-6361/202449893},
  volume       = {689},
  year         = {2024},
}