Biology subjects

Yamada, T.

Publications and source records attributed to Yamada, T..

5 recordsLinked to original sources

bioRxiv2018

Harmonization of resting-state functional MRI data across multiple imaging sites via the separation of site differences into sampling bias and measurement bias

When collecting large neuroimaging data associated with psychiatric disorders, images must be acquired from multiple sites because of the limited capacity of a single site. However, site differences represent the greatest barrier when acquiring multi-site neuroimaging data. We utilized a traveling-subject dataset in conjunction with a multi-site, multi-disorder dataset to demonstrate that site differences are composed of biological sampling bias and engineering measurement bias. Effects on resting-state functional MRI connectivity because of both bias types were greater than or equal to those because of psychiatric disorders. Furthermore, our findings indicated that each site can sample only from among a subpopulation of participants. This result suggests that it is essential to collect large neuroimaging data from as many sites as possible to appropriately estimate the distribution of the grand population. Finally, we developed a novel harmonization method that removed only the measurement bias by using traveling-subject dataset and achieved the reduction of the measurement bias by 29% and the improvement of the signal to noise ratios by 40%.

neuroscience↗

bioRxiv2018

Identification of Functional Targets Reveals that the Suppression of Pumilio mediated mRNA Decay Increases Cell Resistance to DNA Damage in Human Cells

RNA-binding proteins (RBPs) play a pivotal role in gene expression by modulating the stability of transcripts; however, the identification of degradation targets of RBPs remains difficult. Here, we identified 48 target mRNAs of human Pumilio 1 (PUM1), an evolutionally conserved RBP, by combined analysis of transcriptome-wide mRNA stabilities and the binding of mRNAs to PUM1. Here, we developed an approach to identify mRNA targets of Pumilio 1 (PUM1), an evolutionally conserved RBP. By combined analysis of transcriptome-wide mRNA stabilities and the binding of mRNAs to PUM1, we identified 48 mRNAs that both bound to PUM1 and exhibited PUM1-dependent degradation. Analysis of changes in the abundance of PUM1 and its targets in RNA-seq data indicated that DNA-damaging agents negatively regulated PUM1-mediated mRNA decay. Cells exposed to cisplatin had reduced PUM1 abundance and increased PCNA and UBE2A mRNAs, encoding proteins involved in DNA repair by translesion synthesis (TLS). Cells overexpressing PUM1 exhibited impaired DNA synthesis and TLS and increased sensitivity to the cytotoxic effect of cisplatin. Thus, our method identified targets of PUM1-mediated decay and revealed that cells respond to DNA damage by inhibiting PUM1-mediated mRNA decay to activate TLS.

molecular biology↗

bioRxiv2017

A prediction model of working memory across health and psychiatric disease using whole-brain functional connectivity

Individual differences in cognitive function have been shown to correlate with brain-wide functional connectivity, suggesting a common foundation relating connectivity to cognitive function across healthy populations. However, it remains unknown whether this relationship is preserved in cognitive deficits seen in a range of psychiatric disorders. Using machine learning methods, we built a prediction model of working memory function from whole-brain functional connectivity among a healthy population (N = 17, age 19-24 years). We applied this normative model to a series of independently collected resting state functional connectivity datasets (N = 968), involving multiple psychiatric diagnoses, sites, ages (18-65 years), and ethnicities. We found that predicted working memory ability was correlated with actually measured working memory performance in both schizophrenia patients (partial correlation,{rho} = 0.25, P = 0.033, N = 58) and a healthy population (partial correlation,{rho} = 0.11, P = 0.0072, N = 474). Moreover, the model predicted diagnosis-specific severity of working memory impairments in schizophrenia (N = 58, with 60 controls), major depressive disorder (N = 77, with 63 controls), obsessive-compulsive disorder (N = 46, with 50 controls), and autism spectrum disorder (N = 69, with 71 controls) with effect sizes g = -0.68, -0.29, -0.19, and 0.09, respectively. According to the model, each diagnosiss working memory impairment resulted from the accumulation of distinct functional connectivity differences that characterizes each diagnosis, including both diagnosis-specific and diagnosis-invariant functional connectivity differences. Severe working memory impairment in schizophrenia was related not only with fronto-parietal, but also widespread network changes. Autism spectrum disorder showed greater negative connectivity that related to improved working memory function, suggesting that some non-normative functional connections can be behaviorally advantageous. Our results suggest that the relationship between brain connectivity and working memory function in healthy populations can be generalized across multiple psychiatric diagnoses. This approach may shed new light on behavioral variances in psychiatric disease and suggests that whole-brain functional connectivity can provide an individual quantitative behavioral profile in a range of psychiatric disorders.

neuroscience↗

bioRxiv2017

Anterior cingulate cortex connectivity is associated with suppression of behavior in a rat model of chronic pain

A cardinal feature of persistent pain that follows injury is a general suppression of behavior, in which motivation is inhibited in a way that promotes energy conservation and recuperation. Across species, the anterior cingulate cortex (ACC) is associated with the motivational aspects of phasic pain, but whether it mediates motivational functions in persistent pain is less clear. Using burrowing behavior as an marker of non-specific motivated behavior in rodents, we studied the suppression of burrowing following painful CFA or control injection into the right knee-joint of 37 rats (18 with pain), and examined associated neural connectivity with ultra-high-field resting state functional MRI. We found that connectivity between ACC and the subcortex correlated with the reduction in burrowing behavior observed following the pain manipulation. In a full replication study we confirmed these findings in a group of 44 rats (23 with pain). Across both datasets, reduced burrowing was assosciated with increased connectivity between ACC and subcortical structures including hypothalamic/preoptic nuclei and the bed nucleus of the stria terminalis. Together, the findings implicate ACC connectivity as a robust correlate of the motivational aspect of persistent pain in rodents.

neuroscience↗

bioRxiv2017

Clearance of senescent decidual cells by uterine natural killer cells drives endometrial remodeling during the window of implantation

In cycling human endometrium, menstruation is followed by rapid estrogen-dependent growth. Upon ovulation, progesterone and rising cellular cAMP levels activate the transcription factor Forkhead box O1 (FOXO1) in endometrial stromal cells (EnSCs), leading to cell cycle exit and differentiation into decidual cells that control embryo implantation. Here we show that FOXO1 also causes acute senescence of a subpopulation of decidualizing EnSCs in an IL-8 dependent manner. Selective depletion or enrichment of this subpopulation revealed that decidual senescence drives the transient inflammatory response associated with endometrial receptivity. Further, senescent cells prevent differentiation of endometrial mesenchymal stem cells in decidualizing cultures. As the cycle progresses, IL-15 activated uterine natural killer (uNK) cells selectively target and clear senescent decidual cells through granule exocytosis. Our findings reveal that acute decidual senescence governs endometrial rejuvenation and remodeling at embryo implantation, and suggest a critical role for uNK cells in maintaining homeostasis in cycling endometrium.

cell biology↗