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Epigenetic modifications provide powerful means for transmitting information from parent to progeny. As a maternally inherited genome that encodes essential components of the electron transport chain, the mitochondrial genome (mtDNA) is ideally positioned to serve as a conduit for the transgenerational transmission of metabolic information. Here, we provide evidence that mtDNA ofC. eleganscontains the epigenetic mark N6-methyldeoxyadenosine (6mA). Bioinformatic analysis of SMRT sequencing data and methylated DNA IP sequencing data reveal thatC. elegansmtDNA is methylated at high levels in a site-specific manner. We further confirmed that mtDNA contains 6mA by leveraging highly specific anti-6mA antibodies. Additionally, we find that mtDNA methylation is dynamically regulated in response to antimycin, a mitochondrial stressor. Further, 6mA is increased innmad-1mutants and is accompanied by a significant decrease in mtDNA copy number. Our discovery paves the way for future studies to investigate the regulation and inheritance of mitochondrial epigenetics.

Histone modifications are critical for regulating chromatin structure and gene expression. Dysregulation of histone modifications likely contributes to disease states and cancer. Depletion of the chromatin-binding protein BRWD3, a known substrate-specificity factor of the Cul4-DDB1 E3 ubiquitin ligase complex, results in increased in H3K4me1 levels. The underlying mechanism linking BRWD3 and H3K4 methylation, however, has yet to be defined. Here, we show that depleting BRWD3 not only causes an increase in H3K4me1 levels, but also causes a decrease in H3K4me3 levels, indicating that BRWD3 influences H3K4 methylation more broadly. Using immunoprecipitation coupled to quantitative mass spectrometry, we identified an interaction between BRWD3 and the H3K4-specific demethylase 5 (KDM5/Lid), an enzyme that removes tri- and di- methyl marks from H3K4. Moreover, analysis of ChIP-seq data revealed that BRWD3 and KDM5 are significantly co- localized throughout the genome and that sites of H3K4me3 are highly enriched at BRWD3 binding sites. We show that BRWD3 promotes K48-linked polyubiquitination and degradation of KDM5 and that KDM5 degradation is dependent on both BRWD3 and Cul4. Critically, depleting KDM5 fully restores altered H3K4me3 levels and partially restores H3K4me1 levels upon BRWD3 depletion. Together, our results demonstrate that BRWD3 regulates KDM5 activity to balance H3K4 methylation levels.

Direct lifetime measurements via gamma -gamma coincidences using a fast timing detector array consisting of LaBr3(Ce) scintillators has been applied to determine the lifetime of low-lying states in the semimagic (N = 50) nucleus Ru-94. The experiment was carried out as the first in a series of "FAIR-0" experiments with the DESPEC experimental setup at the Facility for Antiproton and Ion Research (FAIR). Excited states in Ru-94 were populated primarily via the beta-delayed proton emission of Pd-95 nuclei, produced in the projectile fragmentation of an 850 MeV/nucleon Xe-124 beam impinging on a 4 g/cm(2) Be-9 target. While the deduced E2 strength for the 2(+) -> 0(+) transition in the yrast cascade follows the expected behavior for conserved seniority symmetry, the intermediate 4(+) -> 2(+) transition exhibits a drastic enhancement of transition strength in comparison with pure-seniority model predictions as well as standard shell model predictions in the f pg proton hole space with respect to doubly magic Sn-100. The anomalous behavior is ascribed to a subtle interference between the wave function of the lowest seniority v = 2, I-pi = 4(+) state and that of a close-lying v = 4 state that exhibits partial dynamic symmetry. In addition, the observed strongly prohibitive 6(+) -> 4(+) transition can be attributed to the same mechanism but with a destructive interference. It is noted that such effects may provide stringent tests of the nucleon-nucleon interactions employed in state-of-the-art theoretical model calculations.

Meiotic drivers are genetic elements that break Mendel’s law of segregation to be transmitted into more than half of the offspring produced by a heterozygote. The success of a driver relies on outcrossing (mating between individuals from distinct lineages) because drivers gain their advantage in heterozygotes. It is, therefore, curious that Schizosaccharomyces pombe, a species reported to rarely outcross, harbors many meiotic drivers. To address this paradox, we measured mating phenotypes in S. pombe natural isolates. We found that the propensity for cells from distinct clonal lineages to mate varies between natural isolates and can be affected both by cell density and by the available sexual partners. Additionally, we found that the observed levels of preferential mating between cells from the same clonal lineage can slow, but not prevent, the spread of a wtf meiotic driver in the absence of additional fitness costs linked to the driver. These analyses reveal parameters critical to understanding the evolution of S. pombe and help explain the success of meiotic drivers in this species., eLife digest The fission yeast, Schizosaccharomyces pombe, is a haploid organism, meaning it has a single copy of each of its genes. S. pombe cells generally carry one copy of each chromosome and can reproduce clonally by duplicating these chromosomes and then dividing into two cells. However, when the yeast are starving, they can reproduce sexually. This involves two cells mating by fusing together to create a ‘diploid zygote’, which contains two copies of each gene. The zygote then undergoes ‘meiosis’, a special type of cell division in which the zygote first duplicates its genome and then divides twice. This results in four haploid spores which are analogous to sperm and eggs in humans that each contain one copy of the genome. The spores will grow and divide normally when conditions improve. The genes carried by each of the haploid spores depend on the cells that formed the zygote. If the two ‘parent’ yeast had the same version or ‘allele’ of a gene, all four spores will have it in their genome. However, if the two parents have different alleles, only 50% of the offspring will carry each version. Although this is usually the case, there are certain alleles, called meiotic drivers, that are transmitted to all offspring even in situations where it is only carried by one parent. Meiotic drivers can be found in many organisms, including mammals, but their behavior is easiest to study in yeast. Meiotic drivers known as killers achieve this by disposing of any ‘sister’ spores that do not inherit the same allele of this gene. This ‘killing’ can only happen when only one of the ‘parents’ carries the driver. This scenario is thought to rarely occur in species that inbreed, as inbreeding leads to both gene copies being the same. However, this does not appear to be the case for S. pombe, which contain a whole family of killer meiotic drivers, the wtf genes, despite also being reported to mainly inbreed. To investigate this contradiction, López Hernández et al. isolated several genetically distinct populations of S.pombe. These isolates were grown together to determine how often the each one would outcross (mate with an individual from a different population) or inbreed. The results found that levels of inbreeding varied between isolates. Next, López Hernández et al. used mathematical modelling and experimental evolution analyses to study how wtf drivers spread amongst these populations. This revealed that wtf genes spread faster in populations with more outcrossing. In some instances, the wtf driver was linked to a gene that could harm the population. In these cases, López Hernández et al. found than inbreeding could purge these drivers and stop them from spreading the dangerous alleles through the population. López Hernández et al. establish a simple experimental system to model driver evolution and experimentally demonstrate how key parameters, such as outcrossing rates, affect the spread of these genes. Understanding how meiotic drivers spread is important, as these systems could potentially be used to modify populations important to humans, such as crops or disease vectors.

Neutron-rich Pm ( Z = 61 ) isotopes were studied by delayed γ -ray spectroscopy at RIBF, RIKEN Nishina Center using the in-flight fission of a 345 MeV/nucleon U 238 beam. A cluster-type Ge detector array, EURICA, was used to measure the delayed γ rays from stopped ions. Isomeric γ decays were observed in Pm 159 and Pm 161 with half-lives of 4.97(12) μ s and 0.79(4) μ s , respectively. Level schemes for Pm 159 and Pm 161 were constructed in this study. The isomeric states of Pm 159 and Pm 161 could be interpreted as two quasiparticle excitations of neutrons with the configurations of ν ( 7 / 2 [ 633 ] ⊗ 5 / 2 [ 523 ] ) and ν ( 7 / 2 [ 633 ] ⊗ 1 / 2 [ 521 ] ) , respectively. They are analogous to the isomers that have been observed systematically in other even-mass N = 98 and N = 100 isotones in this region. A projected shell model calculation was performed and it reproduced the order of three-quasiparticle states only if new Nilsson parameters with an N -dependent spin-orbit interaction were used. This work demonstrates that the strength of spin-orbit interactions in standard Nilsson parameters needs to be modified to study the properties of neutron-rich rare-earth nuclei around A = 165 , and provides new evidence supporting the existence of the deformed N = 98 subshell gap in odd-mass nuclei for the first time.

Bacterial genomes encode various multidrug efflux pumps (MDR) whose specific conditions for fitness advantage are unknown. We show that the efflux pump MdtEF-TolC, in Escherichia coli, confers a fitness advantage during exposure to extreme acid (pH 2). Our flow cytometry method revealed pH-dependent fitness trade-offs between bile acids (a major pump substrate) and salicylic acid, a membrane-permeant aromatic acid that induces a drug resistance regulon but depletes proton motive force (PMF). The PMF drives MdtEF-TolC and related pumps such as AcrAB-TolC. Deletion of mdtE (with loss of the pump MdtEF-TolC) increased the strain’s relative fitness during growth with or without salicylate or bile acids. However, when the growth cycle included a 2-h incubation at pH 2 (below the pH growth range), MdtEF-TolC conferred a fitness advantage. The fitness advantage required bile salts but was decreased by the presence of salicylate, whose uptake is amplified by acid. For comparison, AcrAB-TolC, the primary efflux pump for bile acids, conferred a PMF-dependent fitness advantage with or without acid exposure in the growth cycle. A different MDR pump, EmrAB-TolC, conferred no selective benefit during growth in the presence of bile acids. Without bile acids, all three MDR pumps incurred a large fitness cost with salicylate when exposed at pH 2. These results are consistent with the increased uptake of salicylate at low pH. Overall, we showed that MdtEF-TolC is an MDR pump adapted for transient extreme-acid exposure and that low pH amplifies the salicylate-dependent fitness cost for drug pumps. IMPORTANCE Antibiotics and other drugs that reach the gut must pass through stomach acid. However, little is known of how extreme acid modulates the effect of drugs on gut bacteria. We find that extreme-acid exposure leads to a fitness advantage for a multidrug pump that otherwise incurs a fitness cost. At the same time, extreme acid amplifies the effect of salicylate selection against multidrug pumps. Thus, organic acids and stomach acid could play important roles in regulating multidrug resistance in the gut microbiome. Our flow cytometry assay provides a way to measure the fitness effects of extreme-acid exposure to various membrane-soluble organic acids, including plant-derived nutrients and pharmaceutical agents. Therapeutic acids might be devised to control the prevalence of multidrug pumps in environmental and host-associated habitats.

Background: The evolution of shell structure around doubly-magic exotic nuclei is of great interest in nuclear physics and astrophysics. In the `south-west' region of $^{78}$Ni, the development of deformation might trigger a major shift in our understanding of explosive nucleosynthesis. To this end, new spectroscopic information on key close-lying nuclei is very valuable. Purpose: We intend to measure the isomeric and $\beta$ decay of $^{75}$Co, with one proton- and two neutron-holes relative to $^{78}$Ni, to access new nuclear structure information in $^{75}$Co and its $\beta$-decay daughters $^{75}$Ni and $^{74}$Ni. Methods: The nucleus $^{75}$Co is produced in relativistic in-flight fission reactions of $^{238}$U at the Radioactive Ion Beam Factory (RIBF) in the RIKEN Nishina Center. Its isomeric and $\beta$ decay are studied exploiting the BigRIPS and EURICA setups. Results: We obtain partial $\beta$-decay spectra for $^{75}$Ni and $^{74}$Ni, and report a new isomeric transition in $^{75}$Co. The energy ($E_{\gamma}=1914(2)$ keV) and half-life ($t_{1/2}=13(6)$ $\mu$s) of the delayed $\gamma$ ray lend support for the existence of a $J^{\pi}=(1/2^-)$ isomeric state at 1914(2) keV. A comparison with PFSDG-U shell-model calculations provides good account for the observed states in $^{75}$Ni, but the first calculated $1/2^-$ level in $^{75}$Co, a prolate $K=1/2$ state, is predicted about 1 MeV below the observed $(1/2^-)$ level. Conclusions: The spherical-like structure of the lowest-lying excited states in $^{75}$Ni is proved. In the case of $^{75}$Co, the results suggest that the dominance of the spherical configurations over the deformed ones might be stronger than expected below $^{78}$Ni. Further experimental efforts to discern the nature of the $J^{\pi}=(1/2^-)$ isomer are necessary.

A nuclear spectroscopy experiment was conducted to study α-decay chains stemming from isotopes of flerovium (element Z=114). An upgraded TASISpec decay station was placed behind the gas-filled separator TASCA at the GSI Helmholtzzentrum fur Schwerionenforschung in Darmstadt, Germany. The fusion-evaporation reactions ^{48}Ca+^{242}Pu and ^{48}Ca+^{244}Pu provided a total of 32 flerovium-candidate decay chains, of which two and eleven were firmly assigned to ^{286}Fl and ^{288}Fl, respectively. A prompt coincidence between a 9.60(1)-MeV α particle event and a 0.36(1)-MeV conversion electron marked the first observation of an excited state in an even-even isotope of the heaviest man-made elements, namely ^{282}Cn. Spectroscopy of ^{288}Fl decay chains fixed Q_{α}=10.06(1) MeV. In one case, a Q_{α}=9.46(1)-MeV decay from ^{284}Cn into ^{280}Ds was observed, with ^{280}Ds fissioning after only 518 μs. The impact of these findings, aggregated with existing data on decay chains of ^{286,288}Fl, on the size of an anticipated shell gap at proton number Z=114 is discussed in light of predictions from two beyond-mean-field calculations, which take into account triaxial deformation.

15 pags., 10 figs., 4 tabs., Newly observed decay schemes of the nuclei Sb137 and Sb138 are reported. The neutron-rich Sb isotopes were produced by the in-flight fragmentation of a U238 primary beam with an energy of 345 MeV/nucleon. Several new excited states of Te137 with tentatively assigned spin-parities of (5/2-), (9/2-), and (7/2) have been established which play an important role in the evolution of neutron levels beyond N=82. The study of the ß decay of Sb138 led to a considerable extension of the level scheme of Te138 including the identification of several nonyrast states. The structure of Te137 and Te138 is discussed on the basis of large-scale shell-model calculations performed using two different effective interactions., This work was carried out at the RIBF operated by RIKEN Nishina Center and CNS, University of Tokyo. Part of the WAS3ABi was supported by the Rare Isotope Science Project (RISP) of the Institute for Basic Science (IBS) funded by the Ministry of Science, ICT and Future Planning (MSIP) and National Research Foundation (NRF) of the Republic of Korea (Grant No. 2013M7A1A1075764). This research was supported by NRF of the Republic of Korea (Grants No. 2019R1A6A3A03031564 and No. 2018R1A5A1025563), IBS of the Republic of Korea (Grants No. IBS-R031-D1 and No. IBS-R031-Y1), the Spanish Ministerio de Economía y Competitividad (Grant No. FPA2017-84756-C4-2-P), and JSPS KAKENHI of Japan (Grant No. 25247045). The support from FR-JP LIA is also acknowledged. C.S.L. acknowledges the support from NRF of the Republic of Korea (Grants No. 2017M2A2A6A02071071 and No. 2016R1D1A1A09917463). Z.V. acknowledges the supports from the National Research, Development and Innovation Fund of Hungary, financed under the K18 funding scheme with Project No. K128947 and by the European Regional Development Fund (Grant No. GINOP-2.3.3-15-2016- 00034), as well as by the National Research, Development and Innovation Office NKFIH (Grant No. PD 124717).

6 pags., 4 figs., 2 tabs., The change of the shell structure in atomic nuclei, so-called “nuclear shell evolution”, occurs due to changes of major configurations through particle-hole excitations inside one nucleus, as well as due to variation of the number of constituent protons or neutrons. We have investigated how the shell evolution affects Gamow-Teller (GT) transitions that dominate the β decay in the region below 132Sn using the newly obtained experimental data on a long-lived isomer in 127Ag. The T1/2=67.5(9) ms isomer has been identified with a spin and parity of (27/2+) at an excitation energy of 1942−20+14 keV, and found to decay via an internal transition of an E3 character, which competes with the dominant β-decay branches towards the high-spin states in 127Cd. The underlying mechanism of a strong GT transition from the 127Ag isomer is discussed in terms of configuration-dependent optimization of the effective single-particle energies in the framework of a shell-model approach., Part of the WAS3ABi was supported by the Rare Isotope Science Project which is funded by MSIP and NRF of Korea. This work was supported by the Priority Centers Research Program in Korea (2009-0093817), OTKA contract number K100835, the U.S. DOE, Office of Nuclear Physics (Contract No. DE-AC02-06CH11357), NRF2016R1A5A1013277 and NRF-2013M7A1A1075764, the Spanish Ministerio de Economía y Competitividad under contract FPA2017- 84756-C4-2-P, the European Commission through the Marie Curie Actions call FP7-PEOPLE-2011-IEF (Contract No. 300096), German BMBF under Contract No: 05P12PKFNE, JSPS KAKENHI Grant No. 24740188 and 25247045, the National Natural Science Foundation of China (Nos. 11505302, 11575112, 11775316), the National Key Program for S&T Research and Development (No. 2016YFA0400501), and STFC (UK).

Physics letters / B 816, 136183 (2021). doi:10.1016/j.physletb.2021.136183, Published by North-Holland Publ., Amsterdam

11 pags., 8 figs., 2 tabs., The β decay of the semimagic Sn isotopes Sn136,137,138 has been studied at the Radioactive Isotope Beam Factory at the RIKEN Nishina Center. The first experimental information on excited states was obtained for Sb137 while, in the case of Sb136, the established excitation scheme could be extended by ten previously unidentified levels. In the decay of the most-neutron-rich isotope Sn138, two γ rays were observed for the first time. The new experimental results, in combination with state-of-the-art shell-model calculations, provide the first information with respect to the evolution of the 0g7/2 and 1d5/2 proton single-particle states with increasing neutron number beyond N=84., We thank the staff of the RIKEN Nishina Center accelerator complex for providing high-intensity beams to the experiment. This work was supported by the Spanish Ministerio de Ciencia e Innovación under contracts FPA2014-57196-C5-4-P and FPA2017-84756-C4-2-P and the UK Science and Technology Facilities Council under Grant No. ST/P005101/1. Zs.V. was supported by the European Regional Development Fund (Contract No. GINOP-2.3.3- 15-2016-00034), the National Research Development and Innovation Fund of Hungary (Grant No. K128947), and by RIKEN as short-term International Program Associate.

A new approach for measuring lifetimes of nuclear states at the electronic signal processing stage has been tested. Cerium doped lanthanum bromide inorganic scintillator crystals are used as suitable candidates for fast-timing measurements, in the sub-nanosecond region. The pulse processing of fast timing detectors has been performed using fast amplifiers together with FPGA (field-programmable gate array) based signal discrimination and time measurement in a 10 ps (rms- root mean square) TDC (time-to-digital convertor). The performance from the timing perspective has been tested in an accelerated ion-beam experiment.

We report on new γ-ray spectroscopy results from β decays of In99 and Sn101. 30 new γ rays were observed following the β decay of In99, and inconsistencies in the literature with respect to the γ rays following the β decay of Sn101 were addressed with two confirmed cases and two new transitions. The experimental γ-ray energies, intensities, and coincidence relationships are discussed with shell model calculations, where theoretical β-decay branching ratios from the parent nuclei and γ-ray cascades of excited states from the daughter nuclei were combined to generate hypothetical βγ spectra and βγγ coincidence matrices. The most intense β-delayed γ-ray branches in both Cd99 and In101 were well reproduced with this approach, and several γ rays were assigned to new excited states based on their good agreement with shell model predictions.

Here we present new information on the shape evolution of the very neutron-rich ^{92,94}Se nuclei from an isomer-decay spectroscopy experiment at the Radioactive Isotope Beam Factory at RIKEN. High-resolution germanium detectors were used to identify delayed γ rays emitted following the decay of their isomers. New transitions are reported extending the previously known level schemes. The isomeric levels are interpreted as originating from high-K quasineutron states with an oblate deformation of β∼0.25, with the high-K state in ^{94}Se being metastable and K hindered. Following this, ^{94}Se is the lowest-mass neutron-rich nucleus known to date with such a substantial K hindrance. Furthermore, it is the first observation of an oblate K isomer in a deformed nucleus. This opens up the possibility for a new region of K isomers at low Z and at oblate deformation, involving the same neutron orbitals as the prolate orbitals within the classic Z∼72 deformed hafnium region. From an interpretation of the level scheme guided by theoretical calculations, an oblate deformation is also suggested for the ^{94}Se_{60} ground-state band.