Cellular membranes are complex systems that consist of hundreds of different lipid species. Their investigation often relies on simple bilayer models including few synthetic lipid species. ...Glycerophospholipids (GPLs) extracted from cells are a valuable resource to produce advanced models of biological membranes. Here, we present the optimisation of a method previously reported by our team for the extraction and purification of various GPL mixtures from Pichia pastoris. The implementation of an additional purification step by High Performance Liquid Chromatography-Evaporative Light Scattering Detector (HPLC-ELSD) enabled for a better separation of the GPL mixtures from the neutral lipid fraction that includes sterols, and also allowed for the GPLs to be purified according to their different polar headgroups. Pure GPL mixtures at significantly high yields were produced through this approach. For this study, we utilised phoshatidylcholine (PC), phosphatidylserine (PS) and phosphatidylglycerol (PG) mixtures. These exhibit a single composition of the polar head, i.e., PC, PS or PG, but contain several molecular species consisting of acyl chains of varying length and unsaturation, which were determined by Gas Chromatography (GC). The lipid mixtures were produced both in their hydrogenous (H) and deuterated (D) versions and were used to form lipid bilayers both on solid substrates and as vesicles in solution. The supported lipid bilayers were characterised by quartz crystal microbalance with dissipation monitoring (QCM-D) and neutron reflectometry (NR), whereas the vesicles by small angle X-ray (SAXS) and neutron scattering (SANS). Our results show that despite differences in the acyl chain composition, the hydrogenous and deuterated extracts produced bilayers with very comparable structures, which makes them valuable to design experiments involving selective deuteration with techniques such as NMR, neutron scattering or infrared spectroscopy.
To compare outcomes for patients with hepatocellular carcinoma (HCC) treated with either liver resection or transplantation.
A retrospective, single-institution analysis of 413 HCC patients from 1999 ...to 2009.
A total of 413 patients with HCC underwent surgical resection (n = 106) and transplantation (n = 270) or were listed without receiving transplantation (n = 37). Excluding transplanted patients with incidental tumors (n = 50), 257 patients with suspected HCC were listed with the intent to transplant (ITT). The median diameter of the largest tumor by radiography was 6.0 cm in resected, 3.0 cm in transplanted, and 3.4 cm in the listed-but-not-transplanted patients. Median time to transplant was 48 days. Recurrence rates were 19.8% for resection and 12.1% for all ITT patients. Overall, patient survival for resection versus ITT patients was similar (5-year survival of 53.0% vs 52.0%, not significant). However, for HCC patients with model end-stage liver disease (MELD) scores less than 10 and who radiologically met Milan or UCSF (University of California, San Francisco) criteria, 1-year and 5-year survival rates were significantly improved in resected patients. For patients with MELD score less than 10 and who met Milan criteria, 1-year and 5-year survival were 92.0% and 63.0% for resection (n = 26) versus 83.0% and 41.0% for ITT (n = 73, P = 0.036). For those with MELD score less than 10 and met UCSF criteria, 1-year and 5-year survival was 94.0% and 62.0% for resection (n = 33) versus 81.0% and 40.0% for ITT (n = 78, P = 0.027).
Among known HCC patients with preserved liver function, resection was associated with superior patient survival versus transplantation. These results suggest that surgical resection should remain the first line therapy for patients with HCC and compensated liver function who are candidates for resection.
Carbon/Carbon (C/C) composites derived from the thermoplastic polymer polyetherimide (PEI) were pyrolized up to 1000°C, subsequently carbonized in inert atmosphere up to 2200°C and afterwards ...infiltrated with liquid silicon. The investigation of fibers and matrix with Raman microspectroscopy revealed, that an increased carbonization temperature leads to an increased carbon order as well as an incipient stress-induced graphitization of the carbon matrix close to the fiber surfaces at 2200°C. The derived C/C-SiC samples show a maximum flexural strength of 180MPa with C/C composites treated at 2000°C and monotonically increasing Young’s moduli ranging from 49GPa with C/C preforms treated at 1600°C up to 59GPa after carbonization at 2200°C. The carbon fiber strength was evaluated with a single fiber tensile test, which showed a monotonically increased Young’s modulus and a decrease of the strength after carbonization at 2200°C.
Gaia Data Release 3 Recio-Blanco, A.; de Laverny, P.; Palicio, P. A. ...
Astronomy and astrophysics (Berlin),
06/2023, Letnik:
674
Journal Article
Recenzirano
Odprti dostop
Context.
The chemo-physical parametrisation of stellar spectra is essential for understanding the nature and evolution of stars and of Galactic stellar populations. A worldwide observational effort ...from the ground has provided, in one century, an extremely heterogeneous collection of chemical abundances for about two million stars in total, with fragmentary sky coverage.
Aims.
This situation is revolutionised by the
Gaia
third data release (DR3), which contains the parametrisation of Radial Velocity Spectrometer (RVS) data performed by the General Stellar Parametriser-spectroscopy, GSP-Spec, module. Here we describe the parametrisation of the first 34 months of
Gaia
RVS observations.
Methods.
GSP-Spec estimates the chemo-physical parameters from combined RVS spectra of single stars, without additional inputs from astrometric, photometric, or spectro-photometric BP/RP data. The main analysis workflow described here, MatisseGauguin, is based on projection and optimisation methods and provides the stellar atmospheric parameters; the individual chemical abundances of N, Mg, Si, S, Ca, Ti, Cr, Fe
I
, Fe
II
, Ni, Zr, Ce and Nd; the differential equivalent width of a cyanogen line; and the parameters of a diffuse interstellar band (DIB) feature. Another workflow, based on an artificial neural network (ANN) and referred to with the same acronym, provides a second set of atmospheric parameters that are useful for classification control. For both workflows, we implement a detailed quality flag chain considering different error sources.
Results.
With about 5.6 million stars, the
Gaia
DR3 GSP-Spec all-sky catalogue is the largest compilation of stellar chemo-physical parameters ever published and the first one from space data. Internal and external biases have been studied taking into account the implemented flags. In some cases, simple calibrations with low degree polynomials are suggested. The homogeneity and quality of the estimated parameters enables chemo-dynamical studies of Galactic stellar populations, interstellar extinction studies from individual spectra, and clear constraints on stellar evolution models. We highly recommend that users adopt the provided quality flags for scientific exploitation.
Conclusions.
The
Gaia
DR3 GSP-Spec catalogue is a major step in the scientific exploration of Milky Way stellar populations. It will be followed by increasingly large and higher quality catalogues in future data releases, confirming the
Gaia
promise of a new Galactic vision.
Mitotic spindle formation and chromosome segregation depend critically on kinetochore-microtubule (KT-MT) interactions. A new protein, termed Spindly in Drosophila and SPDL-1 in C. elegans, was ...recently shown to regulate KT localization of dynein, but depletion phenotypes revealed striking differences, suggesting evolutionarily diverse roles of mitotic dynein. By characterizing the function of Spindly in human cells, we identify specific functions for KT dynein. We show that localization of human Spindly (hSpindly) to KTs is controlled by the Rod/Zw10/Zwilch (RZZ) complex and Aurora B. hSpindly depletion results in reduced inter-KT tension, unstable KT fibers, an extensive prometaphase delay, and severe chromosome misalignment. Moreover, depletion of hSpindly induces a striking spindle rotation, which can be rescued by co-depletion of dynein. However, in contrast to Drosophila, hSpindly depletion does not abolish the removal of MAD2 and ZW10 from KTs. Collectively, our data reveal hSpindly-mediated dynein functions and highlight a critical role of KT dynein in spindle orientation.
Gaia Data Release 3 Andrae, R.; Fouesneau, M.; Sordo, R. ...
Astronomy and astrophysics (Berlin),
06/2023, Letnik:
674, Številka:
A27
Journal Article
Recenzirano
Odprti dostop
Context.
The astrophysical characterisation of sources is among the major new data products in the third
Gaia
Data Release (DR3). In particular, there are stellar parameters for 471 million sources ...estimated from low-resolution BP/RP spectra.
Aims.
We present the General Stellar Parameterizer from Photometry (GSP-Phot), which is part of the astrophysical parameters inference system (Apsis). GSP-Phot is designed to produce a homogeneous catalogue of parameters for hundreds of millions of single non-variable stars based on their astrometry, photometry, and low-resolution BP/RP spectra. These parameters are effective temperature, surface gravity, metallicity, absolute
M
G
magnitude, radius, distance, and extinction for each star.
Methods.
GSP-Phot uses a Bayesian forward-modelling approach to simultaneously fit the BP/RP spectrum, parallax, and apparent
G
magnitude. A major design feature of GSP-Phot is the use of the apparent flux levels of BP/RP spectra to derive, in combination with isochrone models, tight observational constraints on radii and distances. We carefully validate the uncertainty estimates by exploiting repeat
Gaia
observations of the same source.
Results.
The data release includes GSP-Phot results for 471 million sources with
G
< 19. Typical differences to literature values are 110 K for
T
eff
and 0.2–0.25 for log
g
, but these depend strongly on data quality. In particular, GSP-Phot results are significantly better for stars with good parallax measurements (
ϖ
/
σ
ϖ
> 20), mostly within 2 kpc. Metallicity estimates exhibit substantial biases compared to literature values and are only useful at a qualitative level. However, we provide an empirical calibration of our metallicity estimates that largely removes these biases. Extinctions
A
0
and
A
BP
show typical differences from reference values of 0.07–0.09 mag. MCMC samples of the parameters are also available for 95% of the sources.
Conclusions.
GSP-Phot provides a homogeneous catalogue of stellar parameters, distances, and extinctions that can be used for various purposes, such as sample selections (OB stars, red giants, solar analogues etc.). In the context of asteroseismology or ground-based interferometry, where targets are usually bright and have good parallax measurements, GSP-Phot results should be particularly useful for combined analysis or target selection.
Lipid–protein interactions play pivotal roles in biological membranes. Electron crystallographic studies of the lens-specific water channel aquaporin-0 (AQP0) revealed atomistic views of such ...interactions, by providing high-resolution structures of annular lipids surrounding AQP0. It remained unclear, however, whether these lipid structures are representative of the positions of unconstrained lipids surrounding an individual protein, and what molecular determinants define the lipid positions around AQP0. We addressed these questions by using molecular dynamics simulations and crystallographic refinement, and calculated time-averaged densities of dimyristoyl-phosphatidylcholine lipids around AQP0. Our simulations demonstrate that, although the experimentally determined crystallographic lipid positions are constrained by the crystal packing, they appropriately describe the behavior of unconstrained lipids around an individual AQP0 tetramer, and thus likely represent physiologically relevant lipid positions.While the acyl chains were well localized, the lipid head groups were not. Furthermore, in silico mutations showed that electrostatic interactions do not play a major role attracting these phospholipids towards AQP0. Instead, the mobility of the protein crucially modulates the lipid localization and explains the difference in lipid density between extracellular and cytoplasmic leaflets. Moreover, our simulations support a general mechanism in which membrane proteins laterally diffuse accompanied by several layers of localized lipids, with the positions of the annular lipids being influenced the most by the protein surface. We conclude that the acyl chains rather than the head groups define the positions of dimyristoyl-phosphatidylcholine lipids around AQP0. Lipid localization is largely determined by the mobility of the protein surface, whereas hydrogen bonds play an important but secondary role.
Persistence of malignant clones is a major determinant of adverse outcome in patients with hematologic malignancies. Despite the fact that the majority of patients with acute myeloid leukemia (AML) ...achieve complete remission after chemotherapy, a large proportion of them relapse as a result of residual malignant cells. These persistent clones have a competitive advantage and can re-establish disease. Therefore, targeting strategies that specifically diminish cell competition of malignant cells while leaving normal cells unaffected are clearly warranted. Recently, our group identified YBX1 as a mediator of disease persistence in JAK2-mutated myeloproliferative neoplasms. The role of YBX1 in AML, however, remained so far elusive. Here, inactivation of YBX1 confirms its role as an essential driver of leukemia development and maintenance. We identify its ability to amplify the translation of oncogenic transcripts, including MYC, by recruitment to polysomal chains. Genetic inactivation of YBX1 disrupts this regulatory circuit and displaces oncogenic drivers from polysomes, with subsequent depletion of protein levels. As a consequence, leukemia cells show reduced proliferation and are out-competed in vitro and in vivo, while normal cells remain largely unaffected. Collectively, these data establish YBX1 as a specific dependency and therapeutic target in AML that is essential for oncogenic protein expression.
Context: As part of the third Gaia Data Release, we present the contributions of the non-stellar and classification modules from the eighth coordination unit (CU8) of the Data Processing and Analysis ...Consortium, which is responsible for the determination of source astrophysical parameters using Gaia data. This is the third in a series of three papers describing the work done within CU8 for this release.
Aims: For each of the five relevant modules from CU8, we summarise their objectives, the methods they employ, their performance, and the results they produce for Gaia DR3. We further advise how to use these data products and highlight some limitations.
Methods: The Discrete Source Classifier (DSC) module provides classification probabilities associated with five types of sources: quasars, galaxies, stars, white dwarfs, and physical binary stars. A subset of these sources are processed by the Outlier Analysis (OA) module, which performs an unsupervised clustering analysis, and then associates labels with the clusters to complement the DSC classification. The Quasi Stellar Object Classifier (QSOC) and the Unresolved Galaxy Classifier (UGC) determine the redshifts of the sources classified as quasar and galaxy by the DSC module. Finally, the Total Galactic Extinction (TGE) module uses the extinctions of individual stars determined by another CU8 module to determine the asymptotic extinction along all lines of sight for Galactic latitudes |b| > 5 degrees.
Results: Gaia DR3 includes 1591 million sources with DSC classifications; 56 million sources to which the OA clustering is applied; 1.4 million sources with redshift estimates from UGC; 6.4 million sources with QSOC redshift; and 3.1 million level 9 HEALPixes of size 0 :013 deg(2) where the extinction is evaluated by TGE.
Conclusions: Validation shows that results are in good agreement with values from external catalogues; for example 90% of the QSOC redshifts have absolute error lower than 0:1 for sources with empty warning flags, while UGC redshifts have a mean error of 0:008 +/- 0:037 if evaluated on a clean set of spectra. An internal validation of the OA results further shows that 30 million sources are located in high confidence regions of the clustering map.
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