We previously showed that infection with vaccinia virus (VV) induces cell motility, characterized by contractility and directed migration. Motility is temporally regulated because cells are motile ...immediately after infection, whereas late in infection motility ceases and cells resettle. Motility and its cessation are accompanied by temporal rearrangements of both the microtubule and the actin networks. Because the F11L gene has previously been implicated in VV-induced migration, we now explore the role of F11L in contractility, migration, the cessation of motility and the cytoskeletal rearrangements. By live cell imaging using a VV that lacks an intact F11L gene, we show that F11L facilitates cell detachment and is required for migration but not for contractility. By light microscopy, F11L expression induces a remodeling of the actin, but not the microtubule, network. The lack of migration correlates with smaller plaques, indicating that this process facilitates cell-to-cell spreading of VV. Late in infection, when motility ceases, cells re-establish cell-to-cell contacts in an F11L-independent manner. We finally show that VV-induced motility and its cessation correlate with a temporal regulation of the guanosine triphosphatase RhoA as well as the expression levels of F11L during the infectious cycle.
Soil organic carbon (SOC) is the largest carbon pool in terrestrial ecosystems and may play a key role in biospheric feedbacks with elevated atmospheric carbon dioxide (CO2) in a warmer future world. ...We examined the simulation results of seven terrestrial biome models when forced with climate projections from four representative-concentration-pathways (RCPs)-based atmospheric concentration scenarios. The goal was to specify calculated uncertainty in global SOC stock projections from global and regional perspectives and give insight to the improvement of SOC-relevant processes in biome models. SOC stocks among the biome models varied from 1090 to 2650 Pg C even in historical periods (ca. 2000). In a higher forcing scenario (i.e., RCP8.5), inconsistent estimates of impact on the total SOC (2099–2000) were obtained from different biome model simulations, ranging from a net sink of 347 Pg C to a net source of 122 Pg C. In all models, the increasing atmospheric CO2 concentration in the RCP8.5 scenario considerably contributed to carbon accumulation in SOC. However, magnitudes varied from 93 to 264 Pg C by the end of the 21st century across biome models. Using the time-series data of total global SOC simulated by each biome model, we analyzed the sensitivity of the global SOC stock to global mean temperature and global precipitation anomalies (ΔT and ΔP respectively) in each biome model using a state-space model. This analysis suggests that ΔT explained global SOC stock changes in most models with a resolution of 1–2 °C, and the magnitude of global SOC decomposition from a 2 °C rise ranged from almost 0 to 3.53 Pg C yr−1 among the biome models. However, ΔP had a negligible impact on change in the global SOC changes. Spatial heterogeneity was evident and inconsistent among the biome models, especially in boreal to arctic regions. Our study reveals considerable climate uncertainty in SOC decomposition responses to climate and CO2 change among biome models. Further research is required to improve our ability to estimate biospheric feedbacks through both SOC-relevant and vegetation-relevant processes.
Abstract Although the adenovirus type 5 (Ad5) E1B 55 kDa protein can bind to RNA in vitro , no UV-light-induced crosslinking of this E1B protein to RNA could be detected in infected cells, under ...conditions in which RNA binding by a known viral RNA-binding protein (the L4 100 kDa protein) was observed readily. Substitution mutations, including substitutions reported to inhibit RNA binding in vitro , did not impair synthesis of viral early or late proteins or alter significantly the efficiency of viral replication in transformed or normal human cells. However, substitutions of conserved residues in the C-terminal segment of an RNA recognition motif specifically inhibited degradation of Mre11. We conclude that, if the E1B 55 kDa protein binds to RNA in infected cells in the same manner as in in vitro assays, this activity is not required for such well established functions as induction of selective export of viral late mRNAs.
KCR channelrhodopsins (K+-selective light-gated ion channels) have received attention as potential inhibitory optogenetic tools but more broadly pose a fundamental mystery regarding how their K+ ...selectivity is achieved. Here, we present 2.5–2.7 Å cryo-electron microscopy structures of HcKCR1 and HcKCR2 and of a structure-guided mutant with enhanced K+ selectivity. Structural, electrophysiological, computational, spectroscopic, and biochemical analyses reveal a distinctive mechanism for K+ selectivity; rather than forming the symmetrical filter of canonical K+ channels achieving both selectivity and dehydration, instead, three extracellular-vestibule residues within each monomer form a flexible asymmetric selectivity gate, while a distinct dehydration pathway extends intracellularly. Structural comparisons reveal a retinal-binding pocket that induces retinal rotation (accounting for HcKCR1/HcKCR2 spectral differences), and design of corresponding KCR variants with increased K+ selectivity (KALI-1/KALI-2) provides key advantages for optogenetic inhibition in vitro and in vivo. Thus, discovery of a mechanism for ion-channel K+ selectivity also provides a framework for next-generation optogenetics.
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•Resolved cryo-EM structures of three K+-selective channelrhodopsins in nanodiscs•Conditions under which natural microbial rhodopsins exhibit a 6-s-cis retinal•A unique K+ selectivity mechanism of KCRs•Design of improved KCR variants including KALI for in vitro and in vivo applications
K+-selective channelrhodopsins (HcKCR1/2) are discovered to work via an asymmetric selectivity gate and a distinct dehydration pathway within the channel; based on the structures obtained here, KCR variants with increased K+ selectivity are generated.
B-factories like the KEKB in Tsukuba, Japan, operate at relatively low energies and thus require detectors with very low material budget in order to minimize multiple scattering. On the other hand, ...front-end chips with short shaping time like the APV25 have to be placed as close to the sensor strips as possible to reduce the capacitive load, which mainly determines the noise figure.
In order to achieve both – minimal material budget and low noise – we developed a readout scheme for double-sided silicon detectors, where the APV25 chips are placed on a flexible circuit, which is glued onto the top side of the sensor. The bottom-side strips are connected by two flexible circuits, which are bent around the edge of the sensor.
This so-called “Origami” design will be utilized to build the Silicon Vertex Detector of the Belle II experiment, which will consist of four layers made from ladders with up to five double-sided silicon strip sensors in a row. Each ladder will be supported by two ribs made of a carbon fiber and Airex foam core sandwich. The heat dissipated by the front-end chips will be removed by a highly efficient two-phase CO2 system. Thanks to the Origami concept, all APV25 chips are aligned in a row and thus can be cooled by a single thin cooling pipe per ladder.
We present the concept and the assembly procedure of the Origami chip-on-sensor modules.
Context. The relativistic effects in the oscillatory damping of magnetic disturbances near two-dimensional X-points are investigated. Aims. By taking displacement current into account, we study new ...features of extremely magnetized systems, in which the Alfvén velocity is almost the speed of light. Methods. The frequencies of the least-damped mode are calculated using linearized relativistic MHD equations for wide ranges of the Lundquist number S and the magnetization parameter σ. Results. The oscillation and decay times depend logarithmically on S in the low resistive limit. This logarithmic scaling is the same as for nonrelativistic dynamics, but the coefficient becomes small as ~σ − 1/2 with increasing σ. These timescales approach constant values in the high resistive limit: the oscillation time becomes a few times the light crossing time, irrespective of σ, and the decay time is proportional to σ so is longer for a highly magnetized system.
Abstract
As the effects of supplementary oxygen on urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG) are poorly understood, urinary 8-OHdG levels (ng/mg creatinine) were determined ...longitudinally on the postnatal day (PND) 1, 3, and 30 in 16 neonates with birth weight < 1000 g. No supplementary oxygen was required in 9 neonates during the first 24 h of life. Urinary 8-OHdG level on PND 1 was inversely correlated with birth weight in these 9 neonates (P = 0.0323) and was higher in four with birth weight < 750 g than five with birth weight > 750 g (41.0 ± 6.9 vs. 5.6 ± 2.7, respectively, P = 0.0200). Median urinary 8-OHdG on PND 1 of these 9 neonates was significantly lower than that of 7 neonates with oxygen (9.3 vs. 60.2, respectively), although there were no significant differences in clinical background, such as birth weight, between the two groups. Five of the 9 did not require supplemental oxygen at all during the first 30 days of life. Median urinary 8-OHdG levels were consistently significantly lower in the 5 neonates than in 11 neonates with oxygen transiently or persistently (9.3 vs. 54.6, 19.1 vs. 61.4, and 28.3 vs. 145 on PND 1, 3, and 30, respectively), although there were no differences in clinical background, such as birth weight, between the two groups. Urinary 8-OHdG on PND 30 was significantly positively correlated with supplemental oxygen dose on PND 30 (P < 0.0001), but not with birth weight in the 16 neonates. These results suggest that higher supplemental oxygen tension caused higher urinary 8-OHdG in this population.
The Belle II Silicon Vertex Detector Friedl, M.; Ackermann, K.; Aihara, H. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
12/2013, Letnik:
732
Journal Article
Recenzirano
Odprti dostop
The KEKB machine and the Belle experiment in Tsukuba (Japan) are now undergoing an upgrade, leading to an ultimate luminosity of 8×1035cm−2s−1 in order to measure rare decays in the B system with ...high statistics.
The previous vertex detector cannot cope with this 40-fold increase of luminosity and thus needs to be replaced. Belle II will be equipped with a two-layer Pixel Detector surrounding the beam pipe, and four layers of double-sided silicon strip sensors at higher radii than the old detector. The Silicon Vertex Detector (SVD) will have a total sensitive area of 1.13m2 and 223,744 channels—twice as many as its predecessor.
All silicon sensors will be made from 150mm wafers in order to maximize their size and thus to reduce the relative contribution of the support structure. The forward part has slanted sensors of trapezoidal shape to improve the measurement precision and to minimize the amount of material as seen by particles from the vertex. Fast-shaping front-end amplifiers will be used in conjunction with an online hit time reconstruction algorithm in order to reduce the occupancy to the level of a few percent at most. A novel “Origami” chip-on-sensor scheme is used to minimize both the distance between strips and amplifier (thus reducing the electronic noise) as well as the overall material budget.
This report gives an overview on the status of the Belle II SVD and its components, including sensors, front-end detector ladders, mechanics, cooling and the readout electronics.
The aetiology of recurrent pregnancy loss (RPL) remains unclear, but it may be related to a possible genetic predisposition together with involvement of environmental factors. We examined the ...relation between RPL and polymorphisms in two genes, glutathione S‐transferases (GST) M1 and T1, which are involved in the metabolism of a wide range of environmental toxins and carcinogens. A case–control study of 115 cases with RPL and 160 controls was conducted. All cases and controls were women resident in Sapporo, Japan and the surrounding area. They were genotyped for polymorphisms of GSTM1 and GSTT1 using PCR‐based methods. We found that 65.2% of the cases with RPL and 45.6% of the controls had the GSTM1 null genotype odds ratio (OR) = 2.23, 95% confidence interval (CI) = 1.36–3.66. On the other hand, 47.0% of the cases and 49.4% of the controls had the GSTT1 null genotype (OR = 0.95; 95% CI = 0.58–1.55). The results suggest that women with GSTM1 null polymorphism may therefore have an increased risk of RPL.
Microbial opsins with a bound chromophore function as photosensitive ion transporters and have been employed in optogenetics for the optical control of neuronal activity. Molecular engineering has ...been utilized to create colour variants for the functional augmentation of optogenetics tools, but was limited by the complexity of the protein-chromophore interactions. Here we report the development of blue-shifted colour variants by rational design at atomic resolution, achieved through accurate hybrid molecular simulations, electrophysiology and X-ray crystallography. The molecular simulation models and the crystal structure reveal the precisely designed conformational changes of the chromophore induced by combinatory mutations that shrink its π-conjugated system which, together with electrostatic tuning, produce large blue shifts of the absorption spectra by maximally 100 nm, while maintaining photosensitive ion transport activities. The design principle we elaborate is applicable to other microbial opsins, and clarifies the underlying molecular mechanism of the blue-shifted action spectra of microbial opsins recently isolated from natural sources.
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