A Non-Motor Microtubule Binding Site Is Essential for the High Processivity and Mitotic Function of Kinesin-8 Kif18A

BACKGROUND: Members of the kinesin-8 subfamily are plus end-directed molecular motors that accumulate at the plus-ends of kinetochore-microtubules (kt-MTs) where they regulate MT dynamics. Loss of vertebrate kinesin-8 function induces hyperstable MTs and elongated mitotic spindles accompanied by severe chromosome congression defects. It has been reported that the motility of human kinesin-8, Kif18A, is required for its accumulation at the plus tips of kt-MTs. METHODOLOGY/FINDINGS: Here, we investigate how Kif18A localizes to the plus-ends of kt-MTs. We find that Kif18A lacking its C-terminus does not accumulate on the tips of kt-MTs and fails to fulfill its mitotic function. In vitro studies reveal that Kif18A possesses a non-motor MT binding site located within its C-proximal 121 residues. Using single molecule measurements we find that Kif18A is a highly processive motor and, furthermore, that the C-terminal tail is essential for the high processivity of Kif18A. CONCLUSION/SIGNIFICANCE: These results show that Kif18A like its yeast orthologue is a highly processive motor. The ability of Kif18A to walk on MTs for a long distance without dissociating depends on a non-motor MT binding site located at the C-terminus of Kif18A. This C-proximal tail of Kif18A is essential for its plus-end accumulation and mitotic function. These findings advance our understanding of how Kif18A accumulates at the tips of kt-MTs to fulfill its function in mitosis

Nonlinear wakefields and electron injection in cluster plasma

Laser and beam driven wakefields promise orders of magnitude increases in electric field gradients for particle accelerators for future applications. Key areas to explore include the emittance properties of the generated beams and overcoming the dephasing limit in the plasma. In this paper, the first in-depth study of the self-injection mechanism into wakefield structures from non-homogeneous cluster plasmas is provided using high-resolution two dimensional particle-in-cell simulations. The clusters which are typical structures caused by ejection of gases from a high-pressure gas jet have a diameter much smaller than the laser wavelength. Conclusive evidence is provided for the underlying mechanism that leads to particle trapping, comparing uniform and cluster plasma cases. The accelerated electron beam properties are found to be tunable by changing the cluster parameters. The mechanism explains enhanced beam charge paired with large transverse momentum and energy which has implications for the betatron x-ray flux. Finally, the impact of clusters on the high-power laser propagation behavior is discussed

Methods for Extremely Sparse-Angle Proton Tomography

Proton radiography is a widely-fielded diagnostic used to measure magnetic structures in plasma. The deflection of protons with multi-MeV kinetic energy by the magnetic fields is used to infer their path-integrated field strength. Here, the use of tomographic methods is proposed for the first time to lift the degeneracy inherent in these path-integrated measurements, allowing full reconstruction of spatially resolved magnetic field structures in three dimensions. Two techniques are proposed which improve the performance of tomographic reconstruction algorithms in cases with severely limited numbers of available probe beams, as is the case in laser-plasma interaction experiments where the probes are created by short, high-power laser pulse irradiation of secondary foil targets. The methods are equally applicable to optical probes such as shadowgraphy and interferometry [M. Kasim et al. Phys. Rev. E 95, 023306 (2017)], thereby providing a disruptive new approach to three dimensional imaging across the physical sciences and engineering disciplines.Comment: 11 pages, 6 figures, companion article to arXiv:2103.1126

Influence of Antihypertensive Treatment on RAAS Peptides in Newly Diagnosed Hypertensive Patients.

(1) Background: Recently, influences of antihypertensive treatment on the renin-angiotensin-aldosterone system (RAAS) has gained attention, regarding a possible influence on inflammatory and anti-inflammatory pathways. We aimed to study the effects of newly initiated antihypertensive drugs on angiotensin (Ang) II and Ang (1-7) as representers of two counter-regulatory axes. (2) Methods: In this randomized, open-label trial investigating RAAS peptides after the initiation of perindopril, olmesartan, amlodipine, or hydrochlorothiazide, Ang II and Ang (1-7) equilibrium concentrations were measured at 8 a.m. and 12 a.m. at baseline and after four weeks of treatment. Eighty patients were randomized (1:1:1:1 fashion). (3) Results: Between the four substances, we found significant differences regarding the concentrations of Ang II (p < 0.0005 for 8 a.m., 12 a.m.) and Ang (1-7) (p = 0.019 for 8 a.m., <0.0005 for 12 a.m.) four weeks after treatment start. Ang II was decreased by perindopril (p = 0.002), and increased by olmesartan (p < 0.0005), amlodipine (p = 0.012), and hydrochlorothiazide (p = 0.001). Ang (1-7) was increased by perindopril and olmesartan (p = 0.008/0.002), but not measurably altered by amlodipine and hydrochlorothiazide (p = 0.317/ 0.109). (4) Conclusion: The initiation of all first line antihypertensive treatments causes early and distinct alterations of equilibrium angiotensin levels. Given the additional AT1R blocking action of olmesartan, RAAS peptides shift upon initiation of perindopril and olmesartan appear to work in favor of the anti-inflammatory axis compared to amlodipine and hydrochlorothiazide

Advantages to a diverging Raman amplifier

The plasma Raman instability can efficiently compress a nanosecond long high-power laser pulse to sub-picosecond duration. Although, many authors envisaged a converging beam geometry for Raman amplification, here we propose the exact opposite geometry; the amplification should start at the intense focus of the seed. We generalise the coupled laser envelope equations to include this non-collimated case. The new geometry completely eradicates the usual trailing secondary peaks of the output pulse, which typically lower the efficiency by half. It also reduces, by orders of magnitude, the initial seed pulse energy required for efficient operation. As in the collimated case, the evolution is self similar, although the temporal pulse envelope is different. A two-dimensional particle-in-cell simulation demonstrates efficient amplification of a diverging seed with only 0.3 mJ energy. The pulse has no secondary peaks and almost constant intensity as it amplifies and diverges

Functional endemism: population connectivity, shifting baselines, and the scale of human experience

Quantifying population connectivity is important for visualizing the spatial and temporal scales that conservation measures act upon. Traditionally, migration based on genetic data has been reported in migrants per generation. However, the temporal scales over which this migration may occur do not necessarily accommodate the scales over which human perturbations occur, leaving the potential for a disconnect between population genetic data and conservation action based on those data. Here, we present a new metric called the “Rule of Memory”, which helps conservation practitioners to interpret “migrants per generation” in the context both of human modified ecosystems and the cultural memory of those doing the modification. Our rule states that clades should be considered functionally endemic regardless of their actual taxonomic designation if the migration between locations is insufficient to maintain a viable population over the timescales of one human generation (20 years). Since larger animals are more likely to be remembered, we quantify the relationship between migrants per human (N) and body mass of the organism in question (M) with the formula N = 10M−1. We then use the coral reef fish Pomacentrus moluccensis to demonstrate the taxonomic and spatial scales over which this rule can be applied. Going beyond minimum viable population literature, this metric assesses the probability that a clade's existence will be forgotten by people throughout its range during a period of extirpation. Because conservation plans are predicated on having well-established baselines, a loss of a species over the range of one human generation evokes the likelihood of that species no longer being recognized as a member of an ecosystem, and thus being excluded in restoration or conservation prioritization