Red blood cells can withstand the harsh mechanical conditions in the vasculature only because the bending rigidity of their plasma membrane is complemented by the shear elasticity of the underlying ...spectrin-actin network. During an infection by the malaria parasite Plasmodium falciparum, the parasite mines host actin from the junctional complexes and establishes a system of adhesive knobs, whose main structural component is the knob-associated histidine rich protein (KAHRP) secreted by the parasite. Here we aim at a mechanistic understanding of this dramatic transformation process. We have developed a particle-based computational model for the cytoskeleton of red blood cells and simulated it with Brownian dynamics to predict the mechanical changes resulting from actin mining and KAHRP-clustering. Our simulations include the three-dimensional conformations of the semi-flexible spectrin chains, the capping of the actin protofilaments and several established binding sites for KAHRP. For the healthy red blood cell, we find that incorporation of actin protofilaments leads to two regimes in the shear response. Actin mining decreases the shear modulus, but knob formation increases it. We show that dynamical changes in KAHRP binding affinities can explain the experimentally observed relocalization of KAHRP from ankyrin to actin complexes and demonstrate good qualitative agreement with experiments by measuring pair cross-correlations both in the computer simulations and in super-resolution imaging experiments.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Reconstructive analysis of retrospective, partly biographical interviews with Luxembourgish care leavers.•Care leavers in Luxembourg have to cope with various transitions – such as school-to-work, ...leaving care and secondary-to-tertiary education – in parallel and in a very short time.•Care arrangements in Luxembourg appear to be on an axis of inequalities. The form as well as the duration and consistency of placement favour the (re-)production of (educational) inequality.•There is a strong interdependency between the care system, care arrangements, possible educational achievements, and agency.•The achievement of agency within the heterogeneous and frequently changing constellations for care leavers depends on the experience of reliable relationships, placement stability in school and in care, and necessary social and even financial support.
This article presents empirical results from a study (2015–2018) on young people leaving care in Luxembourg. A special focus deals with the processes of transitioning from care to work. Education appears to be crucial for a successful transition, as it determines life chances, such as labour market chances, but so far inequality studies have neither researched transitions from care nor have the theoretical concepts developed in inequality research been used to understand the situation of care leavers. They might help to explain the different mechanisms behind the disadvantages of students in foster and residential care and their educational attainment. This paper thus attempts to theorise leaving care from an inequality perspective and the interdependencies with concepts of relational agency, taking into account the heterogeneity among care leavers, their trajectories and achievements (see also Göbel, Hadjar, Karl, Peters, & Jäger, 2020). The main objective of our analysis is to investigate how agency is achieved in the transition from school to work among care leavers, taking into consideration institutional pathways (continuities and discontinuities) in the care and the educational system.
Abstract Observations of OH + are used to infer the interstellar cosmic ray ionization rate in diffuse atomic clouds, thereby constraining the propagation of cosmic rays through and the shielding by ...interstellar clouds, as well as the low energy cosmic ray spectrum. In regions where the H 2 -to-H number density ratio is low, dissociative recombination (DR) is the dominant destruction process for OH + and the DR rate coefficient is important for predicting the OH + abundance and inferring the cosmic ray ionization rate. We have experimentally studied DR of electronically and vibrationally relaxed OH + in its lowest rotational levels, using an electron–ion merged-beams setup at the Cryogenic Storage Ring. From these measurements, we have derived a kinetic temperature rate coefficient applicable to diffuse cloud chemical models, i.e., for OH + in its electronic, vibrational, and rotational ground level. At typical diffuse cloud temperatures, our kinetic temperature rate coefficient is a factor of ∼5 times larger than the previous experimentally derived value and a factor of ∼33 times larger than the value calculated by theory. Our combined experimental and modeling results point to a significant increase for the cosmic ray ionization rate inferred from observations of OH + and H 2 O + , corresponding to a geometric mean of (6.6 ± 1.0) × 10 −16 s −1 , which is more than a factor of 2 larger than the previously inferred values of the cosmic ray ionization rate in diffuse atomic clouds. Combined with observations of diffuse and dense molecular clouds, these findings indicate a greater degree of cosmic ray shielding in interstellar clouds than has been previously inferred.
Worm-like filaments, which are propelled by a tangential homogeneous force along their contour, are studied as they push loads of different shapes and sizes. The resulting dynamics is investigated ...using Langevin dynamics simulations. The effects of size and shape of the load, propulsion strength, and thermal noise are systematically explored. The propulsive force and hydrodynamic friction of the load cause a compression in the filament that results in a buckling instability and versatile motion. Distinct regimes of elongated filaments, curved filaments, beating filaments, and filaments with alternating beating and circular motion are identified, and a phase diagram depending on the propulsion strength and the size of the load is constructed. Characteristic features of the different phases, such as beating frequencies and rotational velocities, are demonstrated to have a power-law dependence on the propulsive force.
Gaseous nitrous acid (HONO) is an important precursor of tropospheric hydroxyl radicals (OH). OH is responsible for atmospheric self-cleansing and controls the concentrations of greenhouse gases like ...methane and ozone. Due to lack of measurements, vertical distributions of HONO and its sources in the troposphere remain unclear. Here, we present a set of observations of HONO and its budget made onboard a Zeppelin airship. In a sunlit layer separated from Earth's surface processes by temperature inversion, we found high HONO concentrations providing evidence for a strong gas-phase source of HONO consuming nitrogen oxides and potentially hydrogen oxide radicals. The observed properties of this production process suggest that the generally assumed impact of HONO on the abundance of OH in the troposphere is substantially overestimated.
Artemisinin resistance in Plasmodium falciparum is associated with nonsynonymous mutations in the Kelch 13 (K13) propeller domain. We found that 12.1% (8/66) of clinical P. falciparum isolates from ...Huye district, Rwanda, exhibited K13 mutations, including R561H, a validated resistance marker. K13 mutations appear to be increasing in this region.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PfEMP1 (erythrocyte membrane protein 1) adhesins play a pivotal role in the pathophysiology of falciparum malaria, by mediating sequestration of
-infected erythrocytes in the microvasculature. PfEMP1 ...variants are expressed by
genes and are presented on membrane elevations, termed knobs. However, the organization of PfEMP1 on knobs is largely unclear. Here, we use super-resolution microscopy and genetically altered parasites expressing a modified
a gene in which the coding sequence of the photoactivatable mEOS2 was inserted to determine the number and distribution of PfEMP1 on single knobs. The data were verified by quantitative fluorescence-activated cell sorting analysis and immuno-electron microscopy together with stereology methods. We show that knobs contain 3.3 ± 1.7 and 4.3 ± 2.5 PfEMP1 molecules, predominantly placed on the knob tip, in parasitized erythrocytes containing wild type and sickle haemoglobin, respectively. The ramifications of our findings for cytoadhesion and immune evasion are discussed.
Three-dimensional matrices often contain highly structured adhesive tracks that require cells to turn corners and bridge non-adhesive areas. Here, we investigate these complex processes using ...micropatterned cell adhesive frames. Spreading kinetics on these matrices depend strongly on initial adhesive position and are predicted by a cellular Potts model (CPM), which reflects a balance between adhesion and intracellular tension. As cells spread, new stress fibers (SFs) assemble periodically and parallel to the leading edge, with spatial intervals of ∼2.5 μm, temporal intervals of ∼15 min, and characteristic lifetimes of ∼50 min. By incorporating these rules into the CPM, we can successfully predict SF network architecture. Moreover, we observe broadly similar behavior when we culture cells on arrays of discrete collagen fibers. Our findings show that ECM geometry and initial cell position strongly determine cell spreading and that cells encode a memory of their spreading history through SF network organization.
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•Spreading trajectories depend strongly on initial adhesive positions•Cells bridge non-adhesive regions with an invaginated actin arc that drives spreading•Stress fibers are generated in a periodic manner behind the advancing front•The stress fiber network retains a spreading memory for ∼50 min
Kassianidou et al. use adhesive micropatterns to recapitulate features of 3D extracellular matrices and to integrate live-cell imaging with mathematical modeling. They find that spreading trajectories are determined by a balance between adhesion energy, surface tension, and line tension, and that cells produce a stress fiber network that encodes the spreading history.
Plasmodium vivax is the second-most common malaria pathogen globally, but is considered very rare in the predominantly Duffy-negative sub-Saharan African population. In 259 malaria patients from ...highland southern Rwanda, we assessed Plasmodium species and Duffy blood group status by polymerase chain reaction (PCR). Plasmodium falciparum, P. vivax, Plasmodium malariae, and Plasmodium ovale were seen in 90.7%, 8.1%, 11.6%, and 5.0%, respectively. Plasmodium vivax occurred more frequently as a monoinfection than in combination with P. falciparum. All P. vivax-infected individuals showed heterozygous Duffy positivity, whereas this was the case for only 3.1% of patients with P. falciparum monoinfection and malaria-negative control subjects (P < 0.01). Based on PCR diagnosis, P. vivax is not rare in southern Rwanda. All episodes of P. vivax were observed in heterozygous Duffy-positive patients, whereas elsewhere in Africa, P. vivax is also reported in Duffy-negative individuals. Refined mapping of Plasmodium species is required to establish control and elimination strategies including all malaria species.
Spectral transfer processes in homogeneous magnetohydrodynamic (MHD) turbulence are investigated analytically by decomposition of the velocity and magnetic fields in Fourier space into helical modes. ...Steady solutions of the dynamical system which governs the evolution of the helical modes are determined, and a stability analysis of these solutions is carried out. The interpretation of the analysis is that unstable solutions lead to energy transfer between the interacting modes while stable solutions do not. From this, a dependence of possible interscale energy and helicity transfers on the helicities of the interacting modes is derived. As expected from the inverse cascade of magnetic helicity in 3-D MHD turbulence, mode interactions with like helicities lead to transfer of energy and magnetic helicity to smaller wavenumbers. However, some interactions of modes with unlike helicities also contribute to an inverse energy transfer. As such, an inverse energy cascade for non-helical magnetic fields is shown to be possible. Furthermore, it is found that high values of the cross-helicity may have an asymmetric effect on forward and reverse transfer of energy, where forward transfer is more quenched in regions of high cross-helicity than reverse transfer. This conforms with recent observations of solar wind turbulence. For specific helical interactions the relation to dynamo action is established. The present analysis provides new theoretical insights into physical processes where inverse cascade and dynamo action are involved, such as the evolution of cosmological and astrophysical magnetic fields and laboratory plasmas.
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