The chloroplast import receptor Toc34 functions as preprotein-regulated GTPase

Toc34 is a protein of the chloroplast outer envelope membrane that acts as receptor for preproteins containing a transit sequence. The recognition of preproteins by Toc34 is regulated by GTP binding and phosphorylation. The phosphorylation site of Toc34 is located at serine 113, close to the postulated triphosphate binding site. This can explain the down-regulation of Toc34 by phosphorylation, resulting in the loss of GTP binding. Vice versa, GTP but not GDP binding of Toc34 influences the phosphorylation. The nucleotide specificity of Toc34 is not only determined by the classical nucleotide binding domains but by a non-typical region at the N-terminus of the protein. As a result, the GTP binding properties are unusual, since the triphosphate moiety of GTP is bound with higher affinity than the purine base. Purified Toc34 hydrolyses GTP at a low rate, which could regulate the receptor function. The rate of hydrolysis is greatly stimulated by a precursor protein

The double well potential in quantum mechanics: a simple, numerically exact formulation

The double well potential is arguably one of the most important potentials in quantum mechanics, because the solution contains the notion of a state as a linear superposition of `classical' states, a concept which has become very important in quantum information theory. It is therefore desirable to have solutions to simple double well potentials that are accessible to the undergraduate student. We describe a method for obtaining the numerically exact eigenenergies and eigenstates for such a model, along with the energies obtained through the Wentzel-Kramers-Brillouin (WKB) approximation. The exact solution is accessible with elementary mathematics, though numerical solutions are required. We also find that the WKB approximation is remarkably accurate, not just for the ground state, but for the excited states as well.Comment: 10 pages, 4 figures; suitable for undergraduate courses in quantum mechanic

A Novel Approach for the Particle-in-Cell Modelling of Gridded Ion Engine Plume Neutralisation

The Particle-in-Cell modelling of gridded ion engine plume neutralisation has been simplified when compared to traditional methods. This results in significantly less computational resources being required. The NSTAR engine was modelled as a reference, where simulated specific impulse values were found to be 5% higher than the real engine. This method will be most suited to rapid prototyping and optimisation studies, where speed of simulations is an important factor

Substrate binding disrupts dimerization and induces nucleotide exchange of the chloroplast GTPase Toc33

GTPases act as molecular switches to control many cellular processes, including signalling, protein translation and targeting. Switch activity can be regulated by external effector proteins or intrinsic properties, such as dimerization. The recognition and translocation of pre-proteins into chloroplasts [via the TOC/TIC (translocator at the outer envelope membrane of chloroplasts/inner envelope membrane of chloroplasts)] is controlled by two homologous receptor GTPases, Toc33 and Toc159, whose reversible dimerization is proposed to regulate translocation of incoming proteins in a GTP-dependent manner. Toc33 is a homodimerizing GTPase. Functional analysis suggests that homodimerization is a key step in the translocation process, the molecular functions of which, as well as the elements regulating this event, are largely unknown. In the present study, we show that homodimerization reduces the rate of nucleotide exchange, which is consistent with the observed orientation of the monomers in the crystal structure. Pre-protein binding induces a dissociation of the Toc33 homodimer and results in the exchange of GDP for GTP. Thus homodimerization does not serve to activate the GTPase activity as discussed many times previously, but to control the nucleotide-loading state. We discuss this novel regulatory mode and its impact on the current models of protein import into the chloroplast

Realistic following behaviors for crowd simulation

International audienceWhile walking through a crowd, a pedestrian experiences a large number of interactions with his neighbors. The nature of these interactions is varied, and it has been observed that macroscopic phenomena emerge from the combination of these local interactions. Crowd models have hitherto considered collision avoidance as the unique type of interactions between individuals, few have considered walking in groups. By contrast, our paper focuses on interactions due to the following behaviors of pedestrians. Following is frequently observed when people walk in corridors or when they queue. Typical macroscopic stop-and-go waves emerge under such traffic conditions. Our contributions are, first, an experimental study on following behaviors, second, a numerical model for simulating such interactions, and third, its calibration, evaluation and applications. Through an experimental approach, we elaborate and calibrate a model from microscopic analysis of real kinematics data collected during experiments. We carefully evaluate our model both at the microscopic and the macroscopic levels. We also demonstrate our approach on applications where following interactions are prominent

Prospects for detecting the 21cm forest from the diffuse intergalactic medium with LOFAR

We discuss the feasibility of the detection of the 21cm forest in the diffuse IGM with the radio telescope LOFAR. The optical depth to the 21cm line has been derived using simulations of reionization which include detailed radiative transfer of ionizing photons. We find that the spectra from reionization models with similar total comoving hydrogen ionizing emissivity but different frequency distribution look remarkably similar. Thus, unless the reionization histories are very different from each other (e.g. a predominance of UV vs. x-ray heating) we do not expect to distinguish them by means of observations of the 21cm forest. Because the presence of a strong x-ray background would make the detection of 21cm line absorption impossible, the lack of absorption could be used as a probe of the presence/intensity of the x-ray background and the thermal history of the universe. Along a random line of sight LOFAR could detect a global suppression of the spectrum from z>12, when the IGM is still mostly neutral and cold, in contrast with the more well-defined, albeit broad, absorption features visible at lower redshift. Sharp, strong absorption features associated with rare, high density pockets of gas could be detected also at z~7 along preferential lines of sight.Comment: 12 pages, 13 figures. MNRAS, in pres

Polymorphism of alpha-1-antitrypsin in hematological malignancies

Alpha-1-antitrypsin (AAT) or serine protease inhibitor A1 (SERPINA1) is an important serine protease inhibitor in humans. The main physiological role of AAT is to inhibit neutrophil elastase (NE) released from triggered neutrophils, with an additional lesser role in the defense against damage inflicted by other serine proteases, such as cathepsin G and proteinase 3. Although there is a reported association between AAT polymorphism and different types of cancer, this association with hematological malignancies (HM) is, as yet, unknown. We identified AAT phenotypes by isoelectric focusing (in the pH 4.2-4.9 range) in 151 serum samples from patients with HM (Hodgkins lymphomas, non-Hodgkins lymphomas and malignant monoclonal gammopathies). Healthy blood-donors constituted the control group (n = 272). The evaluated population of patients as well as the control group, were at Hardy-Weinberg equilibrium for the AAT gene (χ2 = 4.42, d.f.11, p = 0.96 and χ2 = 4.71, d.f.11, p = 0.97, respectively). There was no difference in the frequency of deficient AAT alleles (Pi Z and Pi S) between patients and control. However, we found a significantly higher frequency of PiM1M1 homozygote and PiM1 allele in HM patients than in control (for phenotype: f = 0.5166 and 0.4118 respectively, p = 0.037; for allele: f = 0.7020 and 0.6360 respectively, p = 0.05). In addition, PiM homozygotes in HM-patients were more numerous than in controls (59% and 48%, respectively, p = 0.044). PiM1 alleles and PiM1 homozygotes are both associated with hematological malignancies, although this is considered a functionally normal AAT variant