Showing papers by "Utsunomiya University published in 2020"

COMET Phase-I Technical Design Report

Abstract: The Technical Design for the COMET Phase-I experiment is presented in this paper. COMET is an experiment at J-PARC, Japan, which will search for neutrinoless conversion of muons into electrons in the field of an aluminum nucleus (⁠|$\mu$|–|$e$| conversion, |$\mu^{-}N \rightarrow e^{-}N$|⁠); a lepton flavor-violating process. The experimental sensitivity goal for this process in the Phase-I experiment is |$3.1\times10^{-15}$|⁠, or 90% upper limit of a branching ratio of |$7\times 10^{-15}$|⁠, which is a factor of 100 improvement over the existing limit. The expected number of background events is 0.032. To achieve the target sensitivity and background level, the 3.2 kW 8 GeV proton beam from J-PARC will be used. Two types of detectors, CyDet and StrECAL, will be used for detecting the |$\mu$|–|$e$| conversion events, and for measuring the beam-related background events in view of the Phase-II experiment, respectively. Results from simulation on signal and background estimations are also described.

Roadmap on 3D integral imaging: sensing, processing, and display.

Abstract: This Roadmap article on three-dimensional integral imaging provides an overview of some of the research activities in the field of integral imaging. The article discusses various aspects of the field including sensing of 3D scenes, processing of captured information, and 3D display and visualization of information. The paper consists of a series of 15 sections from the experts presenting various aspects of the field on sensing, processing, displays, augmented reality, microscopy, object recognition, and other applications. Each section represents the vision of its author to describe the progress, potential, vision, and challenging issues in this field.

Calcium dynamics during trap closure visualized in transgenic Venus flytrap.

Abstract: The leaves of the carnivorous plant Venus flytrap, Dionaea muscipula (Dionaea) close rapidly to capture insect prey. The closure response usually requires two successive mechanical stimuli to sensory hairs on the leaf blade within approximately 30 s (refs. 1–4). An unknown biological system in Dionaea is thought to memorize the first stimulus and transduce the signal from the sensory hair to the leaf blade2. Here, we link signal memory to calcium dynamics using transgenic Dionaea expressing a Ca2+ sensor. Stimulation of a sensory hair caused an increase in cytosolic Ca2+ concentration ([Ca2+]cyt) starting in the sensory hair and spreading to the leaf blade. A second stimulus increased [Ca2+]cyt to an even higher level, meeting a threshold that is correlated to the leaf blade closure. Because [Ca2+]cyt gradually decreased after the first stimulus, the [Ca2+]cyt increase induced by the second stimulus was insufficient to meet the putative threshold for movement after about 30 s. The Ca2+ wave triggered by mechanical stimulation moved an order of magnitude faster than that induced by wounding in petioles of Arabidopsis thaliana5 and Dionaea. The capacity for rapid movement has evolved repeatedly in flowering plants. This study opens a path to investigate the role of Ca2+ in plant movement mechanisms and their evolution. A transgenic Venus flytrap expressing a fluorescent calcium sensor allows real-time live quantification of calcium waves triggered by sensory hair movement. The study suggests that calcium levels represent the molecular basis for the memory effect that requires two stimulations within 30 s.

Zucchini consensus motifs determine the mechanism of pre-piRNA production

Abstract: PIWI-interacting RNAs (piRNAs) of between approximately 24 and 31 nucleotides in length guide PIWI proteins to silence transposons in animal gonads, thereby ensuring fertility1. In the biogenesis of piRNAs, PIWI proteins are first loaded with 5'-monophosphorylated RNA fragments called pre-pre-piRNAs, which then undergo endonucleolytic cleavage to produce pre-piRNAs1,2. Subsequently, the 3'-ends of pre-piRNAs are trimmed by the exonuclease Trimmer (PNLDC1 in mouse)3-6 and 2'-O-methylated by the methyltransferase Hen1 (HENMT1 in mouse)7-9, generating mature piRNAs. It is assumed that the endonuclease Zucchini (MitoPLD in mouse) is a major enzyme catalysing the cleavage of pre-pre-piRNAs into pre-piRNAs10-13. However, direct evidence for this model is lacking, and how pre-piRNAs are generated remains unclear. Here, to analyse pre-piRNA production, we established a Trimmer-knockout silkworm cell line and derived a cell-free system that faithfully recapitulates Zucchini-mediated cleavage of PIWI-loaded pre-pre-piRNAs. We found that pre-piRNAs are generated by parallel Zucchini-dependent and -independent mechanisms. Cleavage by Zucchini occurs at previously unrecognized consensus motifs on pre-pre-piRNAs, requires the RNA helicase Armitage, and is accompanied by 2'-O-methylation of pre-piRNAs. By contrast, slicing of pre-pre-piRNAs with weak Zucchini motifs is achieved by downstream complementary piRNAs, producing pre-piRNAs without 2'-O-methylation. Regardless of the endonucleolytic mechanism, pre-piRNAs are matured by Trimmer and Hen1. Our findings highlight multiplexed processing of piRNA precursors that supports robust and flexible piRNA biogenesis.

Common-path multimodal three-dimensional fluorescence and phase imaging system.

Abstract: A stable multimodal system is developed by combining two common-path digital holographic microscopes (DHMs): coherent and incoherent, for simultaneous recording and retrieval of three-dimensional (3-D) phase and 3-D fluorescence imaging (FI), respectively, of a biological specimen. The 3-D FI is realized by a single-shot common-path off-axis fluorescent DHM developed recently by our group. In addition, we accomplish, the phase imaging by another single-shot, highly stable common-path off-axis DHM based on a beam splitter. In this DHM configuration, a beam splitter is used to divide the incoming object beam into two beams. One beam serves as the object beam carrying the useful information of the object under study, whereas another beam is spatially filtered at its Fourier plane by using a pinhole and it serves as a reference beam. This DHM setup, owing to a common-path geometry, is less vibration-sensitive and compact, having a similar field of view but with high temporal phase stability in comparison to a two-beam Mach–Zehnder-type DHM. The performance of the proposed common-path DHM and the multimodal system is verified by conducting various experiments on fluorescent microspheres and fluorescent protein-labeled living cells of the moss Physcomitrella patens . Moreover, the potential capability of the proposed multimodal system for 3-D live fluorescence and phase imaging of the fluorescent beads is also demonstrated. The obtained experimental results corroborate the feasibility of the proposed multimodal system and indicate its potential applications for the analysis of functional and structural behaviors of a biological specimen and enhancement of the understanding of physiological mechanisms and various biological diseases.

The impact of nuclear shape on the emergence of the neutron dripline.

Abstract: Atomic nuclei are composed of a certain number of protons Z and neutrons N. A natural question is how large Z and N can be. The study of superheavy elements explores the large Z limit1,2, and we are still looking for a comprehensive theoretical explanation of the largest possible N for a given Z—the existence limit for the neutron-rich isotopes of a given atomic species, known as the neutron dripline3. The neutron dripline of oxygen (Z = 8) can be understood theoretically as the result of single nucleons filling single-particle orbits confined by a mean potential, and experiments confirm this interpretation. However, recent experiments on heavier elements are at odds with this description. Here we show that the neutron dripline from fluorine (Z = 9) to magnesium (Z = 12) can be predicted using a mechanism that goes beyond the single-particle picture: as the number of neutrons increases, the nuclear shape assumes an increasingly ellipsoidal deformation, leading to a higher binding energy. The saturation of this effect (when the nucleus cannot be further deformed) yields the neutron dripline: beyond this maximum N, the isotope is unbound and further neutrons ‘drip’ out when added. Our calculations are based on a recently developed effective nucleon–nucleon interaction4, for which large-scale eigenvalue problems are solved using configuration-interaction simulations. The results obtained show good agreement with experiments, even for excitation energies of low-lying states, up to the nucleus of magnesium-40 (which has 28 neutrons). The proposed mechanism for the formation of the neutron dripline has the potential to stimulate further thinking in the field towards explaining nucleosynthesis with neutron-rich nuclei. A mechanistic explanation for the origin of the neutron dripline shows that nuclei accommodate the addition of neutrons by becoming increasingly ellipsoidal, up to a maximum number of neutrons, reconciling theory and experiments.

Structural and functional relationships between plasmodesmata and plant endoplasmic reticulum–plasma membrane contact sites consisting of three synaptotagmins

Abstract: Synaptotagmin 1 (SYT1) has been recognised as a tethering factor of plant endoplasmic reticulum (ER)-plasma membrane (PM) contact sites (EPCSs) and partially localises to around plasmodesmata (PD). However, other components of EPCSs associated with SYT1 and functional links between the EPCSs and PD have not been identified. We explored interactors of SYT1 by immunoprecipitation and mass analysis. The dynamics, morphology and spatial arrangement of the ER in Arabidopsis mutants lacking the EPCS components were investigated using confocal microscopy and electron microscopy. PD permeability of EPCS mutants was assessed using a virus movement protein and free green fluorescent protein (GFP) as indicators. We identified two additional components of the EPCSs, SYT5 and SYT7, that interact with SYT1. The mutants of the three SYTs were defective in the anchoring of the ER to the PM. The ER near the PD entrance appeared to be weakly squeezed in the triple mutant compared with the wild-type. The triple mutant suppressed cell-to-cell movement of the virus movement protein, but not GFP diffusion. We revealed major additional components of EPCS associated with SYT1 and suggested that the EPCSs arranged around the PD squeeze the ER to regulate active transport via PD.

Hydroxyl carlactone derivatives are predominant strigolactones in Arabidopsis

Abstract: Strigolactones (SLs) regulate important aspects of plant growth and stress responses. Many diverse types of SL occur in plants, but a complete picture of biosynthesis remains unclear. In Arabidopsis thaliana, we have demonstrated that MAX1, a cytochrome P450 monooxygenase, converts carlactone (CL) into carlactonoic acid (CLA) and that LBO, a 2-oxoglutarate-dependent dioxygenase, can convert methyl carlactonoate (MeCLA) into a metabolite called [MeCLA + 16 Da]. In the present study, feeding experiments with deuterated MeCLAs revealed that [MeCLA + 16 Da] is hydroxymethyl carlactonoate (1'-HO-MeCLA). Importantly, this LBO metabolite was detected in plants. Interestingly, other related compounds, methyl 4-hydroxycarlactonoate (4-HO-MeCLA) and methyl 16-hydroxycarlactonoate (16-HO-MeCLA), were also found to accumulate in lbo mutants. 3-HO-, 4-HO-, and 16-HO-CL were detected in plants, but their expected corresponding metabolites, HO-CLAs, were absent in max1 mutants. These results suggest that HO-CL derivatives may be predominant SLs in Arabidopsis, produced through MAX1 and LBO.

Effects of land use change on turnover and storage of soil organic matter in a tropical forest

Abstract: Land-use change of tropical forests causes loss of soil organic matter and plant productivity. Effects of fallow or plantation vegetation on soil organic matter storage need to be clarified to optimize land-use that maximizes soil organic matter storage and plant productivity. We compared 30-year changes in soil carbon stocks and litter decomposition under different land-uses (primary dipterocarp forest, Macaranga forest, Imperata grassland, transition of Imperata grassland to Acacia plantation, transition of Imperata grassland to oil palm plantation) in Indonesia. The Imperata grassland maximizes soil carbon stocks for up to 10 years due to considerable root litter inputs, but additional organic matter storage is limited over the following 20 years, due to high grass litter decomposability in the less acidified soil. The conversion of Imperata grassland to oil palm plantation causes greatest loss of soil organic matter, whereas Acacia plantation on Imperata grassland or the Macaranga forest maximizes soil carbon stocks due to input of recalcitrant forest litters and reduced microbial activities in the acidified soils. Farmers could adopt short-term ( 10 years) fallow under Acacia plantation on Imperata grassland or Macaranga regeneration forest to maximize soil organic matter storage. The optimum and feasible land-use strategies should be selected based on the length of fallow period and the original acidity of soil.

Linoleic acid, α-linolenic acid, and monolinolenins as antibacterial substances in the heat-processed soybean fermented with Rhizopus oligosporus

Abstract: Antibacterial activities against Staphylococcus aureus and Bacillus subtilis were found in an ethanol fraction of tempe, an Indonesian fermented soybean produced using Rhizopus oligosporus. The ethanol fraction contained free fatty acids, monoglycerides, and fatty acid ethyl esters. Among these substances, linoleic acid and α-linolenic acid exhibited antibacterial activities against S. aureus and B. subtilis, whereas 1-monolinolenin and 2-monolinolenin exhibited antibacterial activity against B. subtilis. The other free fatty acids, 1-monoolein, monolinoleins, ethyl linoleate, and ethyl linolenate did not exhibit bactericidal activities. These results revealed that R. oligosporus produced the long-chain polyunsaturated fatty acids and monolinolenins as antibacterial substances against the Gram-positive bacteria during the fungal growth and fermentation of heat-processed soybean.

Identification of two oxygenase genes involved in the respective biosynthetic pathways of canonical and non-canonical strigolactones in Lotus japonicus.

Abstract: A cytochrome P450 and a 2-oxoglutarate-dependent dioxygenase genes responsible, respectively, for the biosyntheses of canonical and non-canonical strigolactones in Lotus japonicus were identified by transcriptome profiling and mutant screening. Strigolactones (SLs) are a group of apocarotenoids with diverse structures that act as phytohormones and rhizosphere signals. The model legume Lotus japonicus produces both canonical and non-canonical SLs, 5-deoxystrigol (5DS) and lotuslactone (LL), respectively, through oxidation of a common intermediate carlactone by the cytochrome P450 (CYP) enzyme MAX1. However, the pathways downstream of MAX1 and the branching point in the biosyntheses of 5DS and LL have not been elucidated. Here, we identified a CYP and a 2-oxoglutarate-dependent dioxygenase (2OGD) genes responsible, respectively, for the formation of Lotus SLs by transcriptome profiling using RNA-seq and screening of SL-deficient mutants from the Lotus retrotransposon 1 (LORE1) insertion mutant resource. The CYP and 2OGD genes were named DSD and LLD, respectively, after 5DS or LL defective phenotype of the mutants. The involvements of the genes in Lotus SL biosyntheses were confirmed by restoration of the mutant phenotype using Agrobacterium rhizogenes-mediated transformation to generate transgenic roots expressing the coding sequence. The transcript levels of DSD and LLD in roots as well as the levels of 5DS and LL in root exudates were reduced by phosphate fertilization and gibberellin treatment. This study can provide the opportunity to investigate how and why plants produce the two classes of SLs.

Simultaneous introduction of multiple biomacromolecules into plant cells using a cell-penetrating peptide nanocarrier.

Abstract: Plant cells contain groups of biomolecules that participate together in a particular biological process. Exogenous codelivery of multiple biomolecules is an essential step for elucidation of the biological significance of these molecules and enables various biotechnological applications in plants. However, the currently existing biomolecule delivery methods face difficulties in delivering multiple components into plant cells, mediating transgene expression, and maintaining the stability of the numerous components and lead to delays in biomolecular function. Cell-penetrating peptides (CPPs) have demonstrated remarkable abilities to introduce diverse biomolecules into various plant species. Here, we employed the engineered CPP KH9-BP100 as a carrier to deliver multiple biomolecules into plant cells and performed a bimolecular fluorescence complementation assay to assess the simultaneous introduction of multiple biomolecules. We demonstrate that multiple biomolecule/CPP cargos can be simultaneously internalized by a particular plant cell, albeit with different efficiencies. We present a cutting-edge technique for codelivery of multiple biomolecules into plant cells that can be used for elucidation of functional correlations and for metabolic engineering.

Do Phosphate and Cytokinin Interact to Regulate Strigolactone Biosynthesis or Act Independently

Abstract: Strigolactones (SLs) are essential host recognition signals for both root-parasitic plants and arbuscular mycorrhizal (AM) fungi in the rhizosphere, and in planta SLs or their metabolites function as a novel class of plant hormones that regulate various aspects of plant growth through crosstalk with other hormones. Although nutrient availability is one of the important factors influencing SL production and exudation, and phosphate (Pi) deficiency significantly promotes SL production and exudation in host plants of AM fungi, how nutrient availability modulates SL production and exudation remains elusive. Cytokinin (CK), a canonical plant hormone, has extensively been studied as a shoot branching promoter and its biosynthesis is also influenced by mineral nutrients, especially nitrate, indicating that CK might be another key factor that affect SL production and exudation. In the present study, we show that CKs (t-zeatin, benzyladenine, kinetin, and CPPU) applied to hydroponic culture media significantly suppressed the SL levels in both the root exudates and the root tissues of rice plants grown under Pi deficiency. In a split-root system, CK suppressed SL production locally, while Pi affected SL production systemically, suggesting that Pi and CK act on SL production independently in rice plants.

Single-shot common-path off-axis dual-wavelength digital holographic microscopy

Abstract: A single-shot common-path off-axis self-interference dual-wavelength digital holographic microscopic (DHM) system based on a cube beam splitter is demonstrated to expand the phase range in a stepped microstructure and for simultaneous measurement of the refractive index and physical thickness of a specimen. In the system, two laser beams with wavelengths of 532 nm and 632.8 nm are used. These laser beams are combined to transilluminate the object under study, then the object beam is divided into two beams by using a beam splitter oriented in such a way that both the beams propagate in almost the same direction, with an appropriate lateral separation between them. One of the object beams is spatially filtered at its Fourier plane, using a pinhole to generate a reference spherical beam free from the object information. The reference beam interferes with the object beam to form a digital hologram at the faceplate of the image sensor. The phase information is extracted from a single recorded digital hologram using the phase aberration compensation method that is based on principal component analysis (PCA). Owing to the common-path configuration, the system shows high temporal phase stability and it is less vibration-sensitive compared to counterparts such as a Mach-Zehnder type DHM. The performance of the dual-wavelength DHM system is verified in two different application fields by conducting the experiments using microsphere beads and living plant cells.

Hydroxyl carlactone derivatives are predominant strigolactones in Arabidopsis

Abstract: Strigolactones (SLs) regulate important aspects of plant growth and stress responses. Many diverse types of SL occur in plants, but a complete picture of biosynthesis remains unclear. In Arabidopsis thaliana, we have demonstrated that MAX1, a cytochrome P450 monooxygenase, converts carlactone (CL) into carlactonoic acid (CLA), and that LBO, a 2-oxoglutarate-dependent dioxygenase, converts methyl carlactonoate (MeCLA) into a metabolite called [MeCLA+16] Da. In the present study, feeding experiments with deuterated MeCLAs revealed that [MeCLA+16] Da is hydroxymethyl carlactonoate (1’-HO-MeCLA). Importantly, this LBO metabolite was detected in plants. Interestingly, other related compounds, methyl 4-hydroxycarlactonoate (4-HO-MeCLA) and methyl 16-hydroxycarlactonoate (16-HO-MeCLA) were also found to accumulate in lbo mutants. 3-HO-, 4-HO- and 16-HO-CL were detected in plants, but their expected corresponding metabolites, HO-CLAs, were absent in max1 mutants. These results suggest that HO-CL derivatives are predominant SLs in Arabidopsis, produced through MAX1 and LBO.

Development of a Cs-Ru/CeO2 spherical catalyst prepared by impregnation and washing processes for low-temperature decomposition of NH3: Characterization and kinetic analysis results

Abstract: Cl-free Ru/CeO2 spherical catalysts were prepared by incipient wetness impregnation and subsequent washing processes using RuCl3·3H2O and a commercial spherical CeO2 support. Cs addition improved c...

Physical and mechanical properties of wood and their geographic variations in Larix sibirica trees naturally grown in Mongolia.

Abstract: We examined the physical and mechanical properties of wood in Siberian larch (Larix sibirica) trees that grow naturally in five Mongolian provenances (Khentii, Arkhangai, Zavkhan, Khuvsgul, and Selenge) and the geographic variations between them. Five trees with stem diameters of 20 to 30 cm at 1.3 m above ground were collected from each provenance. The mean values of the modulus of elasticity (MOE), modulus of rupture (MOR), compressive strength parallel to grain (CS), and shearing strength (SS) ranged from 7.03 to 9.51 GPa, 79.8 to 103.9 MPa, 46.3 to 51.1 MPa, and 10.4 to 13.0 MPa, respectively. Significant differences were found in radial and tangential shrinkage, MOE, MOR, and SS in wood among the five provenances. In addition, juvenile wood had inferior physical and mechanical properties in comparison to mature wood within and among provenances. Furthermore, there were significant differences in all examined properties, except for CS, in mature wood among the five provenances. Higher correlation coefficients were also obtained in mature wood among all mechanical properties, except for SS.

In-system optimization of a hologram for high-stability parallel laser processing

Abstract: A method for optimizing a computer-generated hologram (CGH) for high-stability laser processing is proposed. The CGH is optimized during laser processing; therefore, unpredicted dynamic changes in the laser processing system, in addition to its static imperfections, are automatically compensated for by exploiting the rewritable capability of the spatial light modulator. Consequently, the short-term and long-term stability are improved, which will contribute to the realization of high-speed, high-precision laser processing. A CGH that generated 36 parallel beams was continuously optimized, and the maximum uniformity reached 0.98, which is higher than reported in previous research. To the best of our knowledge, this is the first demonstration of gradual improvement of parallel laser processing with in-process optimization of the CGH. Furthermore, it was also demonstrated that the performance of the laser processing system against unexpected disturbances was improved.

Prolyl-hydroxyproline, a collagen-derived dipeptide, enhances hippocampal cell proliferation, which leads to antidepressant-like effects in mice

Abstract: Depression has been a mental health issue worldwide. We previously reported that ginger-degraded collagen hydrolysate (GDCH) suppressed depression-like behavior in mice. Furthermore, prolyl-hydroxyproline (PO) and hydroxyprolyl-glycine (OG) were detected in the circulating blood after the oral administration of GDCH. In the present study, PO, but not OG, was detected in the cerebrospinal fluid of rats after the oral administration of GDCH, suggesting that PO is transported from blood to the brain. We then investigated the effects of PO and OG on the depression-like behavior of mice. The oral administration of PO significantly decreased depression-like behavior in the forced swim test. OG had no antidepressant-like effect. In addition, proline and hydroxyproline, components of PO, also had no antidepressant-like effect after their oral administration. PO significantly increased the gene expression of brain-derived neurotrophic factor and nerve growth factor in the hippocampus, and promoted the proliferation of neural progenitor cells in vivo and in vitro. PO also increased the dopamine concentration in the prefrontal cortex. Thus, PO-dependent regulation of neurotrophic function and neurotransmitter may be the mechanism for antidepressant-like behavior. Together, these results demonstrate that PO is an antidepressant bioactive peptide accompanying the proliferation of hippocampal neural progenitor cells.

Association between Plasma Sestrin2 Levels and the Presence and Severity of Coronary Artery Disease.

Abstract: Aims Atherosclerotic disease, such as coronary artery disease (CAD), is recognized to be associated with inflammation and oxidative stress. We investigated the association between CAD and plasma levels of sestrin2 which is one of the stress-inducible antioxidant proteins. Methods We measured plasma sestrin2 levels in 304 patients undergoing elective coronary angiography. The severity of CAD was represented as the numbers of >50% stenotic coronary vessels and segments and the severity score. Results CAD was found in 175 patients, of whom 73 had 1-vessel (1-VD), 59 had 2-vessel (2-VD), and 43 had 3-vessel disease (3-VD). Plasma sestrin2 levels were significantly higher in 175 patients with CAD than in 129 without CAD (median 16.4 vs. 14.2 ng/mL, P 50% stenotic coronary vessels: 14.2 in CAD(-), 15.4 in 1-VD, 17.3 in 2-VD, and 17.7 ng/mL in3-VD (P 16.0 ng/mL) was present in 38% of patients with CAD(-), 47% of 1-VD, 66% of 2-VD, and 53% of 3-VD (P 50% stenotic segments and the severity score (rs = 0.12 and rs = 0.13, P 16.0 ng/mL (P < 0.025). Conclusions Plasma sestrin2 levels in patients with CAD were found to be high and to be associated with the severity of CAD. High sestrin2 levels in patients with CAD may reflect a protective response against the progression of CAD.

Transgenerational inheritance of impaired larval T cell development in zebrafish.

Abstract: Evidence for transgenerational inheritance of epigenetic information in vertebrates is scarce. Aberrant patterns of DNA methylation in gametes may set the stage for transmission into future generations. Here, we describe a viable hypomorphic allele of dnmt1 in zebrafish that causes widespread demethylation of CpG dinucleotides in sperm and somatic tissues. We find that homozygous mutants are essentially normal, with the exception of drastically impaired lymphopoiesis, affecting both larval and adult phases of T cell development. The phenotype of impaired larval (but not adult) T cell development is transmitted to subsequent generations by genotypically wildtype fish. We further find that about 200 differentially methylated regions in sperm DNA of transmitting and non-transmitting males, including hypermethylated sites associated with runx3 and rptor genes, whose reduced activities are associated with impaired larval T cell development. Our results indicate a particular sensitivity of larval T cell development to transgenerationally inherited epimutations.