| 1. |
- Elías-Wolff, Federico, et al.
(författare)
-
Computing Curvature Sensitivity of Biomolecules in Membranes by Simulated Buckling
- 2018
-
Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 14:3, s. 1643-1655
-
Tidskriftsartikel (refereegranskat)abstract
- Membrane curvature sensing, where the binding free energies of membrane-associated molecules depend on the local membrane curvature, is a key factor to modulate and maintain the shape and organization of cell membranes. However, the microscopic mechanisms are not well understood, partly due to absence of efficient simulation methods. Here, we describe a method to compute the curvature dependence of the binding free energy of a membrane associated probe molecule that interacts with a buckled membrane, which has been created by lateral compression of a flat bilayer patch. This buckling approach samples a wide range of curvatures in a single simulation, and anisotropic effects can be extracted from the orientation statistics. We develop an efficient and robust algorithm to extract the motion of the probe along the buckled membrane surface, and evaluate its numerical properties by extensive sampling of three coarse-grained model systems: local lipid density in a curved environment for single-component bilayers, curvature preferences of individual lipids in two-component membranes, and curvature sensing by a homotrimeric transmembrane protein. The method can be used to complement experimental data from curvature partition assays and provides additional insight into mesoscopic theories and molecular mechanisms for curvature sensing.
|
|
| 2. |
- Elias-Wolff, Federico, et al.
(författare)
-
Curvature sensing by cardiolipin in simulated buckled membranes
- 2019
-
Ingår i: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-683X .- 1744-6848. ; 15:4, s. 792-802
-
Tidskriftsartikel (refereegranskat)abstract
- Cardiolipin is a non-bilayer phospholipid with a unique dimeric structure. It localizes to negative curvature regions in bacteria and is believed to stabilize respiratory chain complexes in the highly curved mitochondrial membrane. Cardiolipin's localization mechanism remains unresolved, because important aspects such as the structural basis and strength for lipid curvature preferences are difficult to determine, partly due to the lack of efficient simulation methods. Here, we report a computational approach to study curvature preferences of cardiolipin by simulated membrane buckling and quantitative modeling. We combine coarse-grained molecular dynamics with simulated buckling to determine the curvature preferences in three-component bilayer membranes with varying concentrations of cardiolipin, and extract curvature-dependent concentrations and lipid acyl chain order parameter profiles. Cardiolipin shows a strong preference for negative curvatures, with a highly asymmetric chain order parameter profile. The concentration profiles are consistent with an elastic model for lipid curvature sensing that relates lipid segregation to local curvature via the material constants of the bilayers. These computations constitute new steps to unravel the molecular mechanism by which cardiolipin senses curvature in lipid membranes, and the method can be generalized to other lipids and membrane components as well.
|
|
| 3. |
- Falstad, Niklas, 1987, et al.
(författare)
-
CON-quest: Searching for the most obscured galaxy nuclei
- 2021
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 649
-
Tidskriftsartikel (refereegranskat)abstract
- Context. Some luminous and ultraluminous infrared galaxies (LIRGs and ULIRGs) host extremely compact (r < 100 pc) and dusty nuclei. The high extinction associated with large column densities of gas and dust toward these objects render them hard to detect at many wavelengths. The intense infrared radiation arising from warm dust in these sources can provide a significant fraction of the bolometric luminosity of the galaxy and is prone to excite vibrational levels of molecules such as HCN. This results in emission from the rotational transitions of vibrationally excited HCN (HCN-vib); the brightest emission is found in compact obscured nuclei (CONs; ςHCN-vib > 1 L⊙ pc-2 in the J = 3-2 transition). However, there have been no systematic searches for CONs, and it is unknown how common they are. Aims. We aim to establish how common CONs are in the local Universe (z < 0.08), and whether their prevalence depends on the luminosity or other properties of the host galaxy. Methods. We conducted an Atacama Large Millimeter/submillimeter Array survey of the rotational J = 3-2 transition of HCN-vib in a volume-limited sample of 46 far-infrared luminous galaxies. Results. Compact obscured nuclei are identified in 38-13+18% of the ULIRGs, 21-6+12% of the LIRGs, and 0-0+9% of the lower luminosity galaxies. We find no dependence on the inclination of the host galaxy, but strong evidence of lower IRAS 25 μm to 60 μm flux density ratios (f25/f60) in CONs (with the exception of one galaxy, NGC 4418) compared to the rest of the sample. Furthermore, we find that CONs have stronger silicate features (s9.7 μm), but similar polycyclic aromatic hydrocarbon equivalent widths (EQW6.2 μm) compared to other galaxies. Along with signatures of molecular inflows seen in the far-infrared in most CONs, submillimeter observations also reveal compact, often collimated, outflows. Conclusions. In the local Universe, CONs are primarily found in (U)LIRGs, in which they are remarkably common. As such systems are often highly disturbed, inclinations are difficult to estimate, and high-resolution continuum observations of the individual nuclei are required to determine if the CON phenomenon is related to the inclinations of the nuclear disks. Further studies of the in- A nd outflow properties of CONs should also be conducted to investigate how these are connected to each other and to the CON phenomenon. The lower f25/f60 ratios in CONs as well as the results for the mid-infrared diagnostics investigated (EQW6.2 μm and s9.7 μm) are consistent with the notion that large dust columns gradually shift the radiation from the hot nucleus to longer wavelengths, making the mid- A nd far-infrared "photospheres"significantly cooler than the interior regions. Finally, to assess the importance of CONs in the context of galaxy evolution, it is necessary to extend this study to higher redshifts where (U)LIRGs are more common.
|
|
| 4. |
- Gorski, Mark, 1989, et al.
(författare)
-
A spectacular galactic scale magnetohydrodynamic powered wind in ESO 320-G030
- 2024
-
Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 684
-
Tidskriftsartikel (refereegranskat)abstract
- How galaxies regulate nuclear growth through gas accretion by supermassive black holes (SMBHs) is one of the most fundamental questions in galaxy evolution. One potential way to regulate nuclear growth is through a galactic wind that removes gas from the nucleus. It is unclear whether galactic winds are powered by jets, mechanical winds, radiation, or via magnetohydrodynamic (MHD) processes. Compact obscured nuclei represent a significant phase of galactic nuclear growth. These galaxies hide growing SMBHs or unusual starbursts in their very opaque, extremely compact (r < 100 pc) centres. They are found in approximately 30% of the luminous and ultra-luminous infrared galaxy population. Here, we present high-resolution ALMA observations (∼30 mas, ∼5 pc) of ground-state and vibrationally excited HCN towards ESO 320-G030 (IRAS 11506-3851). ESO 320-G030 is an isolated luminous infrared galaxy known to host a compact obscured nucleus and a kiloparsec-scale molecular wind. Our analysis of these high-resolution observations excludes the possibility of a starburst-driven wind, a mechanically or energy driven active galactic nucleus wind, and exposes a molecular MDH wind. These results imply that the nuclear evolution of galaxies and the growth of SMBHs are similar to the growth of hot cores or protostars where gravitational collapse of the nuclear torus drives a MHD wind. These results mean galaxies are capable, in part, of regulating the evolution of their nuclei without feedback.
|
|
| 5. |
- Lindén, Martin, 1976-
(författare)
-
An early peak in ion channel research
- 2018
-
Ingår i: Nature Physics. - : Springer Science and Business Media LLC. - 1745-2473 .- 1745-2481. ; 14:2, s. 105-105
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 6. |
- Lindén, Martin, 1976-, et al.
(författare)
-
Pointwise error estimates in localization microscopy
- 2017
-
Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Pointwise localization of individual fluorophores is a critical step in super-resolution localization microscopy and single particle tracking. Although the methods are limited by the localization errors of individual fluorophores, the pointwise localization precision has so far been estimated using theoretical best case approximations that disregard, for example, motion blur, defocus effects and variations in fluorescence intensity. Here, we show that pointwise localization precision can be accurately estimated directly from imaging data using the Bayesian posterior density constrained by simple microscope properties. We further demonstrate that the estimated localization precision can be used to improve downstream quantitative analysis, such as estimation of diffusion constants and detection of changes in molecular motion patterns. Finally, the quality of actual point localizations in live cell super-resolution microscopy can be improved beyond the information theoretic lower bound for localization errors in individual images, by modelling the movement of fluorophores and accounting for their pointwise localization uncertainty.
|
|
| 7. |
- Lindén, Martin, 1976-, et al.
(författare)
-
Simulated single molecule microscopy with SMeagol
- 2016
-
Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 32:15, s. 2394-2395
-
Tidskriftsartikel (refereegranskat)abstract
- Summary: SMeagol is a software tool to simulate highly realistic microscopy data based on spatial systems biology models, in order to facilitate development, validation and optimization of advanced analysis methods for live cell single molecule microscopy data.Availability and implementation: SMeagol runs on Matlab R2014 and later, and uses compiled binaries in C for reaction–diffusion simulations. Documentation, source code and binaries for Mac OS, Windows and Ubuntu Linux can be downloaded from http://smeagol.sourceforge.net.
|
|
| 8. |
- Lindén, Martin, 1976-
(författare)
-
Stochastic modeling of motor proteins
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Motor proteins are microscopic biological machines that convert chemical energy into mechanical motion and work. They power a diverse range of biological processes, for example the swimming and crawling motion of bacteria, intracellular transport, and muscle contraction. Understanding the physical basis of these processes is interesting in its own right, but also has an interesting potential for applications in medicine and nanotechnology. The ongoing rapid developments in single molecule experimental techniques make it possible to probe these systems on the single molecule level, with increasing temporal and spatial resolution. The work presented in this thesis is concerned with physical modeling of motor proteins on the molecular scale, and with theoretical challenges in the interpretation of single molecule experiments. First, we have investigated how a small groups of elastically coupled motors collaborate, or fail to do so, when producing strong forces. Using a simple model inspired by the motor protein PilT, we find that the motors counteract each other if the density becomes higher than a certain threshold, which depends on the asymmetry of the system. Second, we have contributed to the interpretation of experiments in which the stepwise motion of a motor protein is followed in real time. Such data is naturally interpreted in terms of first passage processes. Our main conclusions are (1) Contrary to some earlier suggestions, the stepping events do not correspond to the cycle completion events associated with the work of Hill and co-workers. We have given a correct formulation. (2) Simple kinetic models predict a generic mechanism that gives rise to correlations in step directions and waiting times. Analysis of stepping data from a chimaeric flagellar motor was consistent with this prediction. (3) In the special case of a reversible motor, the chemical driving force can be extracted from statistical analysis of stepping trajectories.
|
|
| 9. |
- Lindén, Martin, 1976-, et al.
(författare)
-
Variational Algorithms for Analyzing Noisy Multistate Diffusion Trajectories
- 2018
-
Ingår i: Biophysical Journal. - : CELL PRESS. - 0006-3495 .- 1542-0086. ; 115:2, s. 276-282
-
Tidskriftsartikel (refereegranskat)abstract
- Single-particle tracking offers a noninvasive high-resolution probe of biomolecular reactions inside living cells. However, efficient data analysis methods that correctly account for various noise sources are needed to realize the full quantitative potential of the method. We report algorithms for hidden Markov-based analysis of single-particle tracking data, which incorporate most sources of experimental noise, including heterogeneous localization errors and missing positions. Compared to previous implementations, the algorithms offer significant speedups, support for a wider range of inference methods, and a simple user interface. This will enable more advanced and exploratory quantitative analysis of single-particle tracking data.
|
|
| 10. |
- Nishimura, Y., et al.
(författare)
-
CON-quest: II. Spatially and spectrally resolved HCN/HCO + line ratios in local luminous and ultraluminous infrared galaxies
- 2024
-
Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 686
-
Tidskriftsartikel (refereegranskat)abstract
- Context. Nuclear regions of ultraluminous and luminous infrared galaxies (U/LIRGs) are powered by starbursts and/or active galactic nuclei (AGNs). These regions are often obscured by extremely high columns of gas and dust. Molecular lines in the submillimeter windows have the potential to determine the physical conditions of these compact obscured nuclei (CONs). Aims. We aim to reveal the distributions of HCN and HCO+ emission in local U/LIRGs and investigate whether and how they are related to galaxy properties. Methods. Using the Atacama Large Millimeter/submillimeter Array (ALMA), we have conducted sensitive observations of the HCN J = 3-2 and HCO+J = 3-2 lines toward 23 U/LIRGs in the local Universe (z < 0.07) with a spatial resolution of ~0.3″ ( ~50-400 pc). Results. We detected both HCN and HCO+ in 21 galaxies, only HCN in one galaxy, and neither in one galaxy. The global HCN/HCO+ line ratios, averaged over scales of ~0.5-4 kpc, range from 0.4 to 2.3, with an unweighted mean of 1.1. These line ratios appear to have no systematic trend with bolometric AGN luminosity or star formation rate. The line ratio varies with position and velocity within each galaxy, with an average interquartile range of 0.38 on a spaxel-by-spaxel basis. In eight out of ten galaxies known to have outflows and/or inflows, we found spatially and kinematically symmetric structures of high line ratios. These structures appear as a collimated bicone in two galaxies and as a thin spherical shell in six galaxies. Conclusions. Non-LTE analysis suggests that the high HCN/HCO+ line ratio in outflows is predominantly influenced by the abundance ratio. Chemical model calculations indicate that the enhancement of HCN abundance in outflows is likely due to high-temperature chemistry triggered by shock heating. These results imply that the HCN/HCO+ line ratio can aid in identifying the outflow geometry when the shock velocity of the outflows is sufficiently high to heat the gas.
|
|
| 11. |
- Torén, Kjell, 1952, et al.
(författare)
-
Chronic airflow limitation and its relation to respiratory symptoms among ever-smokers and never-smokers: a cross-sectional study
- 2020
-
Ingår i: Bmj Open Respiratory Research. - : BMJ. - 2052-4439. ; 7:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background The diagnosis of chronic obstructive pulmonary disease is based on the presence of persistent respiratory symptoms and chronic airflow limitation (CAL). CAL is based on the ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1:FVC) after bronchodilation, and FEV1:FVC less than the fifth percentile is often used as a cut-off for CAL. The aim was to investigate if increasing percentiles of FEV1:FVC were associated withany respiratory symptom(cough with phlegm, dyspnoea or wheezing) in a general population sample of never-smokers and ever-smokers. Methods In a cross-sectional study comprising 15 128 adults (50-64 years), 7120 never-smokers and 8008 ever-smokers completed a respiratory questionnaire and performed FEV(1)and FVC after bronchodilation. We calculated theirz-scores for FEV1:FVC and defined the fifth percentile using the Global Lung Function Initiative (GLI) reference value, GLI(5)and increasing percentiles up to GLI(25). We analysed the associations between different strata of percentiles and prevalence ofany respiratory symptomusing multivariable logistic regression for estimation of OR. Results Among all subjects, regardless of smoking habits, the odds ofany respiratory symptomwere elevated up to the GLI(15-20)strata. Among never-smokers, the odds ofany respiratory symptomwere elevated at GLI(<5)(OR 3.57, 95% CI 2.43 to 5.23) and at GLI(5-10)(OR 2.57, 95% CI 1.69 to 3.91), but not at higher percentiles. Among ever-smokers, the odds ofany respiratory symptomwere elevated from GLI(<5)(OR 4.64, 95% CI 3.79 to 5.68) up to GLI(>= 25)(OR 1.33, 95% CI 1.00 to 1.75). Conclusions The association between percentages of FEV1:FVC and respiratory symptoms differed depending on smoking history. Our results support a higher percentile cut-off for FEV1:FVC for never-smokers and, in particular, for ever-smokers.
|
|
| 12. |
- Torén, Kjell, 1952, et al.
(författare)
-
The ratio FEV1/FVC and its association to respiratory symptoms-A Swedish general population study
- 2021
-
Ingår i: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961 .- 1475-097X. ; 41:2, s. 181-191
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic airflow limitation (CAL) can be defined as fixed ratio of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) any respiratory symptom. In a cross-sectional general population study, 15,128 adults (50-64 years of age), 7,120 never-smokers and 8,008 ever-smokers completed a respiratory questionnaire and performed FEV1 and FVC after bronchodilation. We calculated different ratios of FEV1/FVC from 0.40 to 1.0 using 0.70 as reference category. We analysed odds ratios (OR) between different ratios and any respiratory symptom using adjusted multivariable logistic regression. Among all subjects, regardless of smoking habits, the lowest odds for any respiratory symptom was at FEV1/FVC = 0.82, OR 0.48 (95% CI 0.41-0.56). Among never-smokers, the lowest odds for any respiratory symptom was at FEV1/FVC = 0.81, OR 0.53 (95% CI 0.41-0.70). Among ever-smokers, the odds for any respiratory symptom was lowest at FEV1/FVC = 0.81, OR 0.43 (95% CI 0.16-1.19), although the rate of inclining in odds was small in the upper part, that is FEV1/FVC = 0.85 showed similar odds, OR 0.45 (95% CI 0.38-0.55). We concluded that the odds for any respiratory symptoms continuously decreased with higher FEV1/FVC ratios and reached a minimum around 0.80-0.85, with similar results among never-smokers. These results indicate that the optimal threshold associated with respiratory symptoms may be higher than 0.70 and this should be further investigated in prospective longitudinal studies.
|
|
| 13. |
- Volkov, Ivan, et al.
(författare)
-
tRNA tracking for direct measurements of protein synthesis kinetics in live cells
- 2018
-
Ingår i: Nature Chemical Biology. - : NATURE PUBLISHING GROUP. - 1552-4450 .- 1552-4469. ; 14:6, s. 618-626
-
Tidskriftsartikel (refereegranskat)abstract
- Our ability to directly relate results from test-tube biochemical experiments to the kinetics in living cells is very limited. Here we present experimental and analytical tools to directly study the kinetics of fast biochemical reactions in live cells. Dye-labeled molecules are electroporated into bacterial cells and tracked using super-resolved single-molecule microscopy.Trajectories are analyzed by machine-learning algorithms to directly monitor transitions between bound and free states. In particular, we measure the dwell time of tRNAs on ribosomes, and hence achieve direct measurements of translation rates inside living cells at codon resolution. We find elongation rates with tRNA(Phe) that are in perfect agreement with previous indirect estimates, and once fMet-tRNA(fMet) has bound to the 30S ribosomal subunit, initiation of translation is surprisingly fast and does not limit the overall rate of protein synthesis. The experimental and analytical tools for direct kinetics measurements in live cells have applications far beyond bacterial protein synthesis.
|
|
