Biology subjects

Tamura, K.

Publications and source records attributed to Tamura, K..

51 records · Page 3Linked to original sources

bioRxiv2020

Odor mixture perception: can molecular complexity be a factor determining elemental or configural perception?

Odor mixtures can evoke smells that differ from those of their individual odor components. Research has revealed the existence of two perceptual modes, in which a mixture can be perceived as either the original smells of its individual components (elemental) or as a novel smell (configural). However, the factors underlying the perceptual transformation that occurs when smelling a mixture versus its original components remain unclear. Therefore, the present study aimed to identify the properties of odorants that affect olfactory perception of odor mixtures, focusing on the structural complexity of an odorant. We conducted psychophysical experiments in which different groups of participants were instructed to provide olfactory perceptual descriptions of low-, medium-, and high-complexity odor mixtures or components, respectively. To investigate the perceptual modes induced by the mixtures, we compared the participants evaluations between mixtures and components via two types of analyses. First, we compared each olfactory description following quantification via principal component analysis. We then compared data based on seven major olfactory perceptual groups. We observed that odor mixtures composed of low-complexity odorants were perceived as relatively novel smells with regard to both minor (olfactory descriptions) and major (perceptual community) odor qualities than medium- and high-complexity mixtures. Such information may further our understanding of the olfactory perceptual modes of odor mixtures.

neuroscience↗

bioRxiv2020

Expandability differences in learning transfer between computerized and non-computerized games

Computerized and non-computerized games are used in training designed to improve cognitive function. However, it is unclear which properties of the games influence the transfer of cognitive performance. This study aimed to examine the expandability of this transfer according to the properties of training tools. We introduced two training tools (virtual and standard Rubiks Cubes) and examined bidirectional transfer between the two cube types and transfer to other cognitive tasks. The results showed that transfer from the virtual cube to the standard cube was greater relative to that observed from the standard cube to the virtual cube. Regarding transfer to other tasks, cognitive transfer did not differ significantly between the virtual and standard cubes, but the training exerted beneficial effects. These results suggest that transfer expandability differed between computerized and non-computerized games. The findings of the study could contribute to the provision of an effective cognitive training programme.

neuroscience↗

bioRxiv2020

Enhancement of motor performance by a novel training method combining motor imagery and neurofeedback

Motor imagery and neurofeedback have been proposed as motor training approaches, but their effects on the enhancement of motor performance are still controversial. This study aimed to enhance motor performance using a training protocol combining motor imagery and neurofeedback. Seventeen participants were randomly assigned to the training or control group. The training group received real-time electroencephalography activity feedback relative to the motor imagery of the motor action. The control group reiterated the motor imagery of the intended motor action without feedback. The motor performance of the training group was enhanced significantly more than that of the control group. Subsequently, the proposed training protocol was tested in five elite male tennis players to investigate its applicability to sports activities. The motor performance was enhanced in three of these five professional tennis players. Using our training protocol, which combined motor imagery and neurofeedback training, we achieved enhanced motor performance. Furthermore, we could suggest the applicability to sports from the results with world-level tennis players.

neuroscience↗

bioRxiv2020

PLZF is a new substrate of CRBN with thalidomide and 5-hydroxythalidomide

Thalidomide induces cereblon (CRBN)-dependent degradation of proteins. Human cytochrome P450s are thought to provide two monohydroxylated metabolites from thalidomide, and the metabolites are also considered to be involved in thalidomide effects. However, it remains unclear. We report that human PLZF/ZBTB16 is a target protein of CRBN with thalidomide and its derivatives, and that 5-hydroxythalidomide has high potential for degrading PLZF. Using a human transcription factor protein array produced by a wheat cell-free protein synthesis system, PLZF was found to bind to CRBN with thalidomide. PLZF is degraded by the CRL4CRBN complex with thalidomide and its derivatives. Mutagenesis analysis revealed that both 1st and 3rd zinc finger domains conserved in vertebrates are recognized for thalidomide-dependent binding and degradation by CRBN. In chicken limbs, knockdown of Plzf induced skeletal abnormalities, and Plzf was degraded after thalidomide or 5-hydroxythalidomide treatment. Our findings suggest that PLZF is a pivotal substrate involving thalidomide-induced teratogenesis.

pharmacology and toxicology↗

bioRxiv2020

High-Throughput Functional Evaluation of BRCA2 Variants of Unknown Significance

Numerous nontruncating missense variants of the BRCA2 gene have been identified, but there is a lack of convincing evidence, such as familial data, demonstrating their clinical relevance and they thus remain unactionable. To assess the pathogenicity of variants of unknown significance (VUSs) within BRCA2, we developed a novel method, the MANO-B method, for high-throughput functional evaluation utilizing BRCA2-deficient cells and poly(ADP-ribose) polymerase (PARP) inhibitors. The estimated sensitivity and specificity of this assay compared to those of the International Agency for Research on Cancer (IARC) classification system were 95% and 95%, respectively. We classified the pathogenicity of 186 BRCA2 VUSs with our original computational pipeline, resulting in the classification of 126 mutations as "neutral/likely neutral", 23 as "intermediate", and 37 as "deleterious/likely deleterious". We further invented a simplified, on-demand annotation system, the Accurate BRCA Companion Diagnostic (ABCD) test, as a companion diagnostic for PARP inhibitors in patients with unknown BRCA2 VUSs. The ABCD test classification was reproducible and consistent with that of a large-scale MANO-B method.

cancer biology↗

bioRxiv2019

KAKU4-mediated deformation of the vegetative nucleus controls its precedent migration over sperm cells in pollen tubes

A putative nuclear lamina protein, KAKU4, modulates nuclear morphology in Arabidopsis thaliana seedlings but its physiological significance is unknown. KAKU4 was strongly expressed in mature pollen grains, each of which has a vegetative cell and two sperm cells. KAKU4 protein was highly abundant on the envelopes of vegetative nuclei (VNs) and less abundant on the envelopes of sperm cell nuclei (SCNs) in pollen grains and elongating pollen tubes. VN is irregularly shaped in wild-type pollen. However, KAKU4 deficiency caused it to become more spherical. These results suggest that the dense accumulation of KAKU4 is responsible for the irregular shape of the VNs. After a pollen grain germinates, the VN and SCNs migrate to the tip of the pollen tube. In the wild type, the VN preceded the SCNs in 91-93% of the pollen tubes, whereas in kaku4 mutants, the VN trailed the SCNs in 39-58% of the pollen tubes. kaku4 pollen was less competitive than wild-type pollen after pollination, although it had an ability to fertilize. Taken together, our results suggest that controlling the nuclear shape in vegetative cells of pollen grains by KAKU4 ensures the orderly migration of the VN and sperm cells in pollen tubes.\n\nHighlightThe nuclear envelope protein KAKU4 is involved in controlling the migration order of vegetative nuclei and sperm cells in pollen tubes, affecting the competitive ability of pollen for fertilization.

plant biology↗

bioRxiv2019

Reliable confidence intervals for RelTime estimates of evolutionary divergence times

Confidence intervals (CIs) depict the statistical uncertainty surrounding evolutionary divergence time estimates. They capture variance contributed by the finite number of sequences and sites used in the alignment, deviations of evolutionary rates from a strict molecular clock in a phylogeny, and uncertainty associated with clock calibrations. Reliable tests of biological hypotheses demand reliable CIs. However, current non-Bayesian methods may produce unreliable CIs because they do not incorporate rate variation among lineages and interactions among clock calibrations properly. Here, we present a new analytical method to calculate CIs of divergence times estimated using the RelTime method, along with an approach to utilize multiple calibration uncertainty densities in these analyses. Empirical data analyses showed that the new methods produce CIs that overlap with Bayesian highest posterior density (HPD) intervals. In the analysis of computer-simulated data, we found that RelTime CIs show excellent average coverage probabilities, i.e., the true time is contained within the CIs with a 95% probability. These developments will encourage broader use of computationally-efficient RelTime approach in molecular dating analyses and biological hypothesis testing.

evolutionary biology↗

bioRxiv2019

A new method for inferring timetrees from temporally sampled molecular sequences

Pathogen timetrees are phylogenies scaled to time. They reveal the temporal history of a pathogen spread through the populations as captured in the evolutionary history of strains. These timetrees are inferred by using molecular sequences of pathogenic strains sampled at different times. That is, temporally sampled sequences enable the inference of sequence divergence times. Here, we present a new approach (RelTime with Dated Tips [RTDT]) to estimating pathogen timetrees based on the relative rate framework underlying the RelTime approach. RTDT does not require many of the priors demanded by Bayesian approaches, and it has light computing requirements. We found RTDT to be accurate on simulated datasets evolved under a variety of branch rates models. Interestingly, we found two non-Bayesian methods (RTDT and Least Squares Dating [LSD]) to perform similar to or better than the Bayesian approaches available in BEAST and MCMCTree programs. RTDT method was found to generally outperform all other methods for phylogenies in with autocorrelated evolutionary rates. In analyses of empirical datasets, RTDT produced dates that were similar to those from Bayesian analyses. Speed and accuracy of the new method, as compared to the alternatives, makes it appealing for analyzing growing datasets of pathogenic strains. Cross-platform MEGA X software, freely available from http://www.megasoftware.net, now contains the new method for use through a friendly graphical user interface and in high-throughput settings.\n\nAUTHOR SUMMARYPathogen timetrees trace the origins and evolutionary histories of strains in populations, hosts, and outbreaks. The tips of these molecular phylogenies often contain sampling time information because the sequences were generally obtained at different times during the disease outbreaks and propagation. We have developed a new method for inferring timetrees for phylogenies with tip dates, which improves on widely-used Bayesian methods (e.g., BEAST) in computational efficiency and does not require prior specification of population parameters, branch rate model, or clock model. We performed extensive computer simulation and found that RTDT performed better than the other methods for the estimation of divergence times at deep node in phylogenies where evolutionary rates were autocorrelated. The new method is available in the cross-platform MEGA software package that provides a graphical user interface, and allows use via a command line in scripting and high throughput analysis (www.megasoftware.net).

evolutionary biology↗

bioRxiv2018

Detecting modifications in proteomics experiments with Param-Medic

Searching tandem mass spectra against a peptide database requires accurate knowledge of various experimental parameters, including machine settings and details of the sample preparation protocol. In some cases, such as in re-analysis of public data sets, this experimental metadata may be missing or inaccurate. We describe a method for automatically inferring the presence of various types of modifications, including stable-isotope and isobaric labeling, tandem mass tags, and phosphorylation, directly from a given set of mass spectra. We demonstrate the sensitivity and specificity of the proposed approach, and we provide open source Python and C++ implementations in a new version of the software tool Param-Medic.

bioinformatics↗

bioRxiv2018

Chemo-mechanical Coupling in the Transport Cycle of a Type II ABC Transporter

AT P -binding cassette (ABC) transporters are integral membrane proteins that translocate a wide range of substrates across biological membranes, harnessing free energy from the binding and hydrolysis of ATP. To understand the mechanism of the inward- to outward-facing transition that could be achieved by tight regulation of ATPase activity through extensive conformational changes of the protein, we applied template-based iterative all-atom molecular dynamics (MD) simulation to the heme ABC transporter BhuUV-T. The simulations, together with biased MDs, predict two new conformations of the protein, namely, occluded (Occ) and outward-facing (OF) conformations. The comparison between the inward-facing crystal structure and the predicted two structures shows atomic details of the gating motions at the transmembrane helices and dimerization of the nucleotide-binding domains (NBDs). The MD simulations further reveal a novel role of the ABC signature motifs (LSGG[Q/E]) at the NBDs in decelerating ATPase activity in the Occ form through sporadic flipping of the side chains of the LSGG[Q/E] catalytic serine residues. The orientational changes are coupled to loose NBD dimerization in the Occ state, whereas they are blocked in the OF form where the NBDs are tightly dimerized. The chemo-mechanical coupling mechanism may apply to other types of ABC transporters having the conserved LSGG[Q/E] signature motifs.

biochemistry↗

bioRxiv2018

An averaging strategy to reduce variability in target-decoy estimates of false discovery rate

Decoy database search with target-decoy competition (TDC) provides an intuitive, easy-to-implement method for estimating the false discovery rate (FDR) associated with spectrum identifications from shotgun proteomics data. However, the procedure can yield different results for a fixed dataset analyzed with different decoy databases, and this decoy-induced variability is particularly problematic for smaller FDR thresholds, datasets or databases. In such cases, the nominal FDR might be 1% but the true proportion of false discoveries might be 10%. The averaged TDC protocol combats this problem by exploiting multiple independently shuffled decoy databases to provide an FDR estimate with reduced variability. We provide a tutorial introduction to aTDC, describe an improved variant of the protocol that offers increased statistical power, and discuss how to deploy aTDC in practice using the Crux software toolkit.

bioinformatics↗

bioRxiv2018

Modelling the emergence of an egalitarian society in the n-player game framework

Unlike other primates, human foragers have an egalitarian society. Therefore, the evolution of egalitarian behaviour has been the subject of long-standing debate in a wide variety of disciplines. A recent hypothesis states that a social control against potentially dominant individuals played an important role in the emergence of an egalitarian society, although this has not been modelled directly. In the present study, we modelled this hypothesis based on the n-player game framework, in which the owner, who may attempt to monopolise resources, could be punished by a coalition of other group members. Our results suggest that a potentially despotic payoff structure can promote the evolution of egalitarian behaviour. Besides, large group size, small cost of competition, and variation in the strengths of individuals can promote the evolution of egalitarian behaviour. Our results suggest the importance of both social control against dominant individuals and benefits of a coalition for the evolution of egalitarian behaviour.

animal behavior and cognition↗

bioRxiv2018

Adaptive landscape of protein variation in human exomes

The human genome contains hundreds of thousands of missense mutations. However, only a handful of these variants are known to be adaptive, which implies that adaptation through protein sequence change is an extremely rare phenomenon in human evolution. Alternatively, existing methods may lack the power to pinpoint adaptive variation. We have developed and applied an Evolutionary Probability Approach (EPA) to discover candidate adaptive polymorphisms (CAPs) through the discordance between allelic evolutionary probabilities and their observed frequencies in human populations. EPA reveals thousands of missense CAPs, which suggest that a large number of previously optimal alleles had experienced a reversal of fortune in the human lineage. We explored non-adaptive mechanisms to explain CAPs, including the effects of demography, mutation rate variability, and negative and positive selective pressures in modern humans. Our analyses suggest that a large proportion of CAP alleles have increased in frequency due to beneficial selection. This conclusion is supported by the facts that a vast majority of adaptive missense variants discovered previously in humans are CAPs, and that hundreds of CAP alleles are protective in genotype-phenotype association data. Our integrated phylogenomic and population genetic EPA approach predicts the existence of thousands of signatures of non-neutral evolution in the human proteome. We expect this collection to be enriched in beneficial variation. EPA approach can be applied to discover candidate adaptive variation in any protein, population, or species for which allele frequency data and reliable multispecies alignments are available.

evolutionary biology↗

bioRxiv2017

RelTime relaxes the strict molecular clock throughout the phylogeny

The RelTime method estimates divergence times when evolutionary rates vary among lineages. Theoretical analyses show that RelTime relaxes the strict molecular clock throughout a molecular phylogeny, and it performs well in the analysis of empirical and computer simulated datasets in which evolutionary rates are variable. Lozano-Fernandez et al. (2017) found that the application of RelTime to one metazoan dataset (Erwin et al. 2011) produced equal rates for several ancient lineages, which led them to speculate that RelTime imposes a strict molecular clock for deep animal divergences. RelTime does not impose a strict molecular clock. The pattern observed by Lozano-Fernandez et al. (2017) was a result of the use of an option to assign the same rate to lineages in RelTime when the rates are not statistically significantly different. The median rate difference was 5% for many deep metazoan lineages for Erwin et al. (2011) dataset, so the rate equality was not rejected. In fact, RelTime analysis with and without the option to test rate differences produced very similar time estimates. We found that the Bayesian time estimates vary widely depending on the root priors assigned, and that the use of less restrictive priors produce Bayesian divergence times that are concordant with those from RelTime for Erwin et al. (2011) dataset. Therefore, it is prudent to discuss Bayesian estimates obtained under a range of priors in any discourse about molecular dating, including method comparisons.

evolutionary biology↗

bioRxiv2017

Theoretical foundation of the RelTime method for estimating divergence times from variable evolutionary rates

RelTime estimates divergence times by relaxing the assumption of a strict molecular clock in a phylogeny. It showed excellent performance in estimating divergence times for both simulated and empirical molecular sequence datasets in which evolutionary rates varied extensively throughout the tree. RelTime is computationally efficient and scales well with increasing size of datasets. Until now, however, RelTime has not had a formal mathematical foundation. Here, we show that the basis of the RelTime approach is a relative rate framework (RRF) that combines comparisons of evolutionary rates in sister lineages with the principle of minimum rate change between an evolutionary lineage and its descendants. We present analytical solutions for estimating relative lineage rates and divergence times under RRF. We also discuss the relationship of RRF with other approaches, including the Bayesian framework. We conclude that RelTime will be also useful for phylogenies with branch lengths derived not only from molecular data, but also morphological and biochemical traits.

evolutionary biology↗