A Mother’s Sacrifice: The contribution of asymmetric cell division to lifespan regulation in Saccharomyces cerevisiae.

Aging determinants are asymmetrically distributed during cell division in S. cerevisiae, which leads to production of an immaculate, age-free daughter cell. During this process, damaged components are sequestered and retained in the mother cell, while higher functioning organelles and rejuvenating factors are transported to and/or enriched in the bud. Here, we will describe the key quality control mechanisms in budding yeast that contribute to asymmetric cell division of aging determinants, with a specific focus on mitochondria. We find that the actin cytoskeleton, which drives transport of many cellular components in yeast, plays a crucial role in segregating fit from less fit mitochondria between mother and daughter cells. Since actin cables are dynamic structures that undergo retrograde flow, treadmilling from the bud towards the mother cell, they acts as filters to prevent damaged, dysfunctional mitochondria from being inherited by the daughter cell. This asymmetry has a direct impact on regulation of daughter cell fitness. A direct counterpart to mitochondrial motility events is anchorage of the organelle, which occurs in the mother tip, mother cortex, and bud tip in budding yeast. We find that mitochondrial fusion, together with tethering protein, serves to promote anchorage and accumulation of mitochondria at the bud tip. This anchorage must be properly maintained, as ectopic increase in mitochondrial anchorage can disrupt quality control mechanisms aimed at promoting asymmetric cell division

Effects of galactic magnetic field on the UHECR correlation studies with starburst galaxies

We estimate the biases caused by the coherent deflection of cosmic rays due to the Galactic magnetic field (GMF) in maximum-likelihood analysis for searches of ultrahigh-energy cosmic ray (UHECR) sources in the literature. We simulate mock event datasets with a set of assumptions for the starburst galaxy (SBG) source model (arXiv:1801.06160), coherent deflection by a GMF model (arXiv:1204.3662,arXiv:1210.7820), and mixed-mass composition (arXiv:1901.03338); we then conduct a maximum-likelihood analysis without accounting for the GMF in the same manner as previous studies. We find that the anisotropic fraction $f_{\rm ani}$ is estimated systematically lower than the true value. We estimate the true parameters which are compatible with the best-fit parameters reported in (arXiv:1801.06160), and find that except for a narrow region with a large anisotropic fraction and small separation angular scale a wide parameter space is still compatible with the experimental results. We also develop a maximum-likelihood method that takes into account the GMF model and confirm in the MC simulations that we can estimate the true parameters within a 1$\sigma$ contour under the ideal condition that we know the event-by-event mass and the GMF

Discovery of novel enzyme genes involved in the conversion of an arylglycerol-β-aryl ether metabolite and their use in generating a metabolic pathway for lignin valorization

Microbial conversions known as “biological funneling” have attracted attention for their ability to upgrade heterogeneous mixtures of low-molecular-weight aromatic compounds obtained by chemical lignin depolymerization. β-hydroxypropiovanillone (HPV) and its analogs can be obtained by chemoselective catalytic oxidation of lignin using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone/tert-butyl nitrite/O2, followed by cleavage of arylglycerol-β-aryl ether with zinc. Sphingobium sp. strain SYK-6 can degrade HPV generated by the catabolism of arylglycerol-β-aryl ether through 2-pyrone-4,6-dicarboxylate (PDC), a promising platform chemical. Therefore, production of PDC from HPV can be achieved using the HPV catabolic pathway. However, the pathway and genes involved in the catabolism of vanilloyl acetic acid (VAA) generated during HPV catabolism have not been investigated. In the present study, we isolated SLG_24960 (vceA), which encodes an enzyme that converts VAA into a coenzyme A (CoA) derivative of vanillate (vanilloyl-CoA) from SYK-6, by shotgun cloning. The analysis of a vceA mutant indicated that this gene is not required for VAA conversion in vivo, but it encodes a major enzyme catalyzing CoA-dependent VAA conversion in vitro. We also identified SLG_12450 (vceB), whose product can convert vanilloyl-CoA to vanillate. Enzyme genes besides vceA and vceB, which are necessary for the conversions of HPV to VAA and of vanillate to PDC, were introduced and expressed in Pseudomonas putida. The resulting engineered strain completely converted 1 mM HPV into PDC after 24 h. Our results suggest that the enzyme genes that are not required for the catabolic pathway in microorganisms but can be used for the conversion of target substrates are buried in microbial genomes. These genes are, thus, useful for designing metabolic pathways to produce value-added metabolites.PostprintPeer reviewe

Evaluation of internal margins for prostate for step and shoot intensity‐modulated radiation therapy and volumetric modulated arc therapy using different margin formulas

[Purpose] This feasibility study evaluated the intra-fractional prostate motion using an ultrasound image-guided system during step and shoot intensity-modulated radiation therapy (SS-IMRT) and volumetric modulated arc therapy (VMAT). Moreover, the internal margins (IMs) using different margin formulas were calculated. [Methods] Fourteen consecutive patients with prostate cancer who underwent SS-IMRT (n = 5) or VMAT (n = 9) between March 2019 and April 2020 were considered. The intra-fractional prostate motion was observed in the superior–inferior (SI), anterior–posterior (AP), and left–right (LR) directions. The displacement of the prostate was defined as the displacement from the initial position at the scanning start time, which was evaluated using the mean ± standard deviation (SD). IMs were calculated using the van Herk and restricted maximum likelihood (REML) formulas for SS-IMRT and VMAT. [Results] For SS-IMRT, the maximum displacements of the prostate motion were 0.17 ± 0.18, 0.56 ± 0.86, and 0.18 ± 0.59 mm in the SI, AP, and LR directions, respectively. For VMAT, the maximum displacements of the prostate motion were 0.19 ± 0.64, 0.22 ± 0.35, and 0.14 ± 0.37 mm in the SI, AP, and LR directions, respectively. The IMs obtained for SS-IMRT and VMAT were within 2.3 mm and 1.2 mm using the van Herk formula and within 1.2 mm and 0.8 mm using the REML formula. [Conclusions] This feasibility study confirmed that intra-fractional prostate motion was observed with SS-IMRT and VMAT using different margin formulas. The IMs should be determined according to each irradiation technique using the REML margin

Numerical study of air-entraining and submerged vortices in a pump sump

Numerical detection of harmful vortices in pump sumps, such as an air-entraining vortex (AEV) and a submerged vortex (SMV), is crucially important to develop the drain pump machinery. We performed numerical simulations of the benchmark experiments of the pump sump conducted by Matsui et al. (2006 and 2016) using the OpenFOAM and compared the simulation results with the experimental data considering the effects of turbulence model, grid density and detection method of the vortices. We studied the threshold of the gas-liquid volume fraction of the VOF method and the second invariant of velocity gradient tensor to identify AEV and SMV. The methods proposed in the present paper were found to be very effective for the detection of the vortices, and the simulation results by RANS with the SST k-omega model successfully reproduced the experimental data. LES with the Smagorinsky model, however, was sensitive to the grid system and difficult to reproduce the experimental data even for the finest grid system having 3.7 million cells in the present study

Characterization of Fluorescent Proteins for Three- and Four-Color Live-Cell Imaging in S. cerevisiae

Saccharomyces cerevisiae are widely used for imaging fluorescently tagged protein fusions. Fluorescent proteins can easily be inserted into yeast genes at their chromosomal locus, by homologous recombination, for expression of tagged proteins at endogenous levels. This is especially useful for incorporation of multiple fluorescent protein fusions into a single strain, which can be challenging in organisms where genetic manipulation is more complex. However, the availability of optimal fluorescent protein combinations for 3-color imaging is limited. Here, we have characterized a combination of fluorescent proteins, mTFP1/mCitrine/mCherry for multicolor live cell imaging in S. cerevisiae. This combination can be used with conventional blue dyes, such as DAPI, for potential four-color live cell imaging

The brightest UV-selected galaxies in protoclusters at z∼4z\sim4: Ancestors of Brightest Cluster Galaxies?

We present the results of a survey of the brightest UV-selected galaxies in protoclusters. These proto-brightest cluster galaxy (proto-BCG) candidates are drawn from 179 overdense regions of $g$-dropout galaxies at $z\sim4$ from the Hyper Suprime-Cam Subaru Strategic Program identified previously as good protocluster candidates. This study is the first to extend the systematic study of the progenitors of BCGs from $z\sim2$ to $z\sim4$. We carefully remove possible contaminants from foreground galaxies and, for each structure, we select the brightest galaxy that is at least 1 mag brighter than the fifth brightest galaxy. We select 63 proto-BCG candidates and compare their properties with those of galaxies in the field and those of other galaxies in overdense structures. The proto-BCG candidates and their surrounding galaxies have different rest-UV color $(i - z)$ distributions to field galaxies and other galaxies in protoclusters that do not host proto-BCGs. In addition, galaxies surrounding proto-BCGs are brighter than those in protoclusters without proto-BCGs. The image stacking analysis reveals that the average effective radius of proto-BCGs is $\sim28\%$ larger than that of field galaxies. The $i-z$ color differences suggest that proto-BCGs and their surrounding galaxies are dustier than other galaxies at $z\sim4$. These results suggest that specific environmental effects or assembly biasses have already emerged in some protoclusters as early as $z \sim 4$, and we suggest that proto-BCGs have different star formation histories than other galaxies in the same epoch.Comment: 18 pages, 11 figures, Accepted for publication in Ap

Pin1 and WWP2 regulate GluR2 Q/R site RNA editing by ADAR2 with opposing effects

While the essential role of the adenosine deaminase ADAR2 in RNA editing is well established, how it is regulated remains largely unknown. Here, the prolyl isomerase Pin1 and the E3 ubiquitin ligase WWP2 are shown to play a role in regulating ADAR2 localisation and stability