Max Planck Institute for Medical Research

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    561975 research outputs found

    LISA Non-Linear Dynamics and Tilt-To-Length Coupling

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    For the LISA mission, Tilt-To-Length (TTL) coupling is expected to be one of the dominant instrumental noise contributions after laser frequency noise is suppressed based, on assumptions on the size of the coupling and angular jitter levels. This work uses for the first time a closed-loop, non-linear, and time-varying dynamics implementation to simulate detailed angular jitters for the spacecraft and optical benches. In turn, this gives an improved expectation of the TTL contribution to the interferometric output. It is shown that the TTL coupling impact is limited given current estimates on the size of coupling coefficients. A time-domain Least Squares estimator is used to infer the TTL parameters from the simulated measurements. The bias and correlations limit the estimator in the case of regular datasets with amplified TTL coefficients to a relative error of 10%10\%, but the subtraction of the TTL signal still works well. For lower readout noises, the estimation error diverges, which can be mitigated using a regularization term. Alternatively, using sinusoidal maneuvers improves the inference to a high accuracy of 0.1%0.1\% for TTL coefficients around the expected level, removing all correlations in the inferred parameters. This validates the maneuver design by Wegener et al. (2025) in this closed-loop setting

    Distribution of rickettsial endosymbionts and their possible transmission within the Pleodorina japonica (Volvocales, Chlorophyceae) population

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    The green alga Pleodorina japonica is an interesting volvocine species that harbors abundant rickettsial endosymbionts ("MIDORIKO") within its cytoplasm. However, the diversity and transmission of these endosymbionts within the species remain unclear. In this study, we examined the presence or absence of "MIDORIKO" and the genetic diversity in 21 culture strains of the host P. japonica population from various localities in Japan. Genomic polymerase chain reactions using "MIDORIKO"-specific primers and 4',6-diamidino-2-phenylindole-staining demonstrated that only five of the 21 strains harbored "MIDORIKO." The 16S ribosomal DNA sequences of "MIDORIKO" from these five strains (1148 bp) were identical to each other and distinct from the sequences of the rickettsial endosymbionts harbored by other algal species and protists, suggesting that "MIDORIKO" from P. japonica is specific to P. japonica. The phylogenetic results for the 21 host strains, which were resolved based on three nuclear genes encoding oxygen-evolving enhancer protein 1, F1F0 ATP synthase subunit beta and actin disagreed significantly. None of the three gene phylogenies supported the close relationship of the five "MIDORIKO"-harboring strains. A recombination test using the three concatenated genes provided strong evidence of recombination. Therefore, gene flow by sexual reproduction has likely occurred in the natural habitats of P. japonica. The transmission of "MIDORIKO" among different P. japonica genotypes could also be considered to occur via sexual reproduction, although it is likely infrequent via that method given the sporadic nature of "MIDORIKO" within the P. japonica population. Although P. japonica exhibits homothallic sexual reproduction, the present genetic data demonstrate that it is undoubtedly a biological species

    Biomolecular condensates sustain pH gradients at equilibrium through charge neutralization

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    Electrochemical gradients are essential to the functioning of cells and form across membranes using active transporters. Here we show in contrast that condensed biomolecular systems-often termed condensates-sustain pH gradients without any external energy input. By studying individual condensates on the micrometre scale using a microdroplet platform, we reveal dense-phase pH shifts towards conditions of minimal electrostatic repulsion. We demonstrate that protein condensates can drive substantial alkaline and acidic gradients, which are compositionally tunable and can extend to complex architectures sustaining multiple unique pH conditions simultaneously. Through in silico characterization of human proteomic condensate networks, we further highlight potential wide-ranging electrochemical properties emerging from condensation in nature, while correlating intracellular condensate pH gradients with complex biomolecular composition. Together, the emergent nature of condensation shapes distinct pH microenvironments, thereby creating a regulatory mechanism to modulate biochemical activity in living and artificial systems

    Resubstantivising data protection rights

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    Macropinocytic Uptake and pH-Responsive Endolysosomal Processing Drive Sustained Chemotherapeutic Efficacy of High-Load Core@Shell Nanocarriers in Colorectal Cancer

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    Poor tumor targeting, strong toxic side effects, and high drug resistance remain clinical challenges for conventional chemotherapy. Here, it is reported that drug-cocktail core@shell nanocarriers are developed for the codelivery of lipophilic irinotecan (ITC) and the hydrophilic 5-fluorouracil (5-FU) metabolite (FdUMP), a commonly used combination in chemotherapy regimens for colorectal cancer. With a drug loading of 57% by mass, these nanocarriers achieve one of the highest reported drug payloads for a chemotherapeutic drug cocktail. Crucially, using a probe-based imaging strategy with mechanistically responsive fluorescent reporters, we found that after slow uptake predominantly via macropinocytosis, the nanocarriers rapidly traffic to endolysosomal compartments, where the acidic environment triggers sustained drug release. In alignment with the slow uptake and trafficking behavior, these nanocarriers induce a delayed yet prolonged cytotoxic effect in colorectal cancer cells. These findings provide the first direct evidence linking slow uptake, intracellular trafficking, and progressive nuclear delivery of nanocarrier cargo to the delayed yet sustained cytotoxic response. Together, this work highlights both the therapeutic potential of these nanocarriers and the broad applicability of the probe-based imaging approach to elucidate the mechanistic intracellular trafficking and nuclear delivery of different types of nanoparticles delivering cargoes beyond cancer chemotherapy in various cellular models

    Carbon-13 Centerband-Only Detection of EXchange with Dynamic Nuclear Polarization

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    The magic-angle spinning NMR technique, Centerband-Only Detection of EXchange (CODEX), can be used to determine the oligomerization state of molecules when combined with site-specific labeling. Calibrated with amino acid crystals, the method is successfully applied to proteins, primarily combined with 19F labeling. The use of 13C spins for CODEX-based oligomer determination in proteins is hampered by limited sensitivity of 13C spins due to the low gyromagnetic ratio of 13C and the presence of natural abundance background spins which contribute to the observed CODEX decay. The use of CODEX is proposed in conjunction with dynamic nuclear polarization (DNP) at low temperature to increase sensitivity. It is necessary to correct for effects of 13C present at natural abundance. A (PDSD) proton driven spin diffusion-based correction is demonstrated to be effective when the isotropic chemical shifts of the natural abundance background are distinct from the labeled site. Using a 13C-ζ-phenylalanine-labeled GB1 sample, it is demonstrated that the autocorrelation peak decay observed in a series of PDSD spectra can be utilized to correct for the additional dephasing and recover the expected CODEX decay curve. With 13C-γ-phenylalanine labeling and 13C-depleted background, mixing times up to 1500 s are demonstrated

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