Biology subjects

Tani, N.

Publications and source records attributed to Tani, N..

27 records · Page 2Linked to original sources

bioRxiv2021

Frequency band coupling with high-frequency activities during seizures shifts from θ band in tonic phase to δ band in clonic phase

ObjectiveTo clarify variations in the relationship between high-frequency activities (HFAs) and low-frequency bands from the tonic to the clonic phase in focal to bilateral tonic-clonic seizures (FBTCS), using phase-amplitude coupling. MethodsThis retrospective study enrolled six patients with drug-resistant focal epilepsy who underwent intracranial electrode placement for presurgical invasive electroencephalography at Osaka University Hospital (July 2018-July 2019). We used intracranial electrodes to record seizures in focal epilepsy (11 FBTCS). The magnitude of synchronization index (SIm) and receiver-operating characteristic (ROC) analysis were used to analyze the coupling between HFA amplitude (80-250 Hz) and lower frequencies phase. ResultsThe {theta} (4-8 Hz)-HFA SIm peaked in the tonic phase, whereas the {delta} (2-4 Hz)-HFA SIm peaked in the clonic phase. ROC analysis indicated that the {delta}-HFA SIm discriminated well the clonic from the tonic phase. ConclusionsThe main low-frequency band modulating the HFA shifted from the {theta} band in the tonic phase to the {delta} band in the clonic phase. SignificanceIn FBTCS, low-frequency band coupling with HFA amplitude varies temporally. Especially, the {delta} band is specific to the clonic phase. These results suggest dynamically neurophysiological changes in the thalamus or basal ganglia throughout FBTCS. HighlightsO_LIThe {theta} band (4-8 Hz) was mainly coupled with high-frequency activity (HFA) in the tonic phase of focal to bilateral tonic-clonic seizures (FBTCS). C_LIO_LIThe {delta} band (2-4 Hz) was mainly coupled with HFA in the clonic phase of FBTCS. C_LIO_LIThe magnitude of the synchronization index related to {delta}-HFA phase-amplitude coupling discriminated well the clonic from the tonic phase. C_LI

physiology↗

bioRxiv2021

Meiosis-specific ZFP541 repressor complex promotes meiotic prophase exit during spermatogenesis

During spermatogenesis, meiosis is accompanied by robust alteration in gene expression and chromatin status. However, it remained elusive how meiotic transcriptional program is established to ensure completion of meiotic prophase. Here, we identified a novel protein complex consisting of germ-cell-specific zinc-finger protein ZFP541 and its interactor KCTD19 as the key transcriptional regulator for meiotic prophase exit. Our genetic study showed that ZFP541 and KCTD19 are co-expressed from pachytene onward and play an essential role in the completion of meiotic prophase program in the testis. Furthermore, our ChIP-seq and transcriptome analyses revealed that ZFP541 binds to and suppresses a broad range of genes whose function is associated with biological processes of transcriptional regulation and covalent chromatin modification. The present study demonstrated that germ-cell specific ZFP541-KCTD19 containing complex promotes meiotic prophase exit in males, and triggers reconstruction of the transcription network and chromatin organization leading to post-meiotic development.

developmental biology↗

bioRxiv2020

Swallowing-related neural oscillation: An intracranial EEG study

Swallowing is a unique movement due to the indispensable orchestration of voluntary and involuntary movement. The transition from voluntary to involuntary swallowing is executed on the order of milliseconds. We hypothesized that its neural mechanism is revealed by high frequency cortical activities. Eight epileptic participants fitted with intracranial electrodes over the orofacial cortex were asked to swallow a water bolus, and cortical oscillatory changes, including high {gamma} band (75-150 Hz) and {beta} band (13-30 Hz) were investigated at the time of mouth-opening, water-injection, and swallowing. High {gamma} power increases associated with mouth-opening were observed in the ventrolateral prefrontal cortex with water-injection in the lateral central sulcus and with swallowing in the region along the Sylvian fissure. Mouth-opening induced a {beta} power decrease, which continued until the completion of swallowing. The high {gamma} burst activity was focal and specific to swallowing, however, the {beta} activities were extensive and not specific to swallowing. At the boundary time between voluntary and involuntary swallowing, swallowing-related high {gamma} power achieved the peak, and subsequently, the power decreased. We demonstrated three distinct activities related to mouth-opening, water-injection, and swallowing induced at different timings, using high {gamma} activities. The peak of high {gamma} power related to swallowing suggests that during voluntary swallowing phases, the cortex is the main driving force for swallowing rather than the brain stem.

neuroscience↗

bioRxiv2020

Visualization of Phase-Amplitude Coupling Using Rhythmic High-Frequency Activity

ObjectiveHigh-frequency activities (HFAs) and phase-amplitude coupling (PAC) are gaining attention as key neurophysiological biomarkers for studying human epilepsy. We aimed to clarify and visualize how HFAs are modulated by the phase of low-frequency bands during seizures. MethodsWe used intracranial electrodes to record seizures of symptomatic focal epilepsy (15 seizures in seven patients). Ripples (80-250 Hz), as representative of HFAs, were evaluated along with PAC. The synchronization index (SI), representing PAC, was used to analyze the coupling between the amplitude of ripples and the phase of lower frequencies. We created a video in which the intracranial electrode contacts were represented by circles that were scaled linearly to the power changes of ripple. ResultsThe main low frequency band modulating ictal-ripple activities was the {theta} band (4-8 Hz), and after completion of ictal-ripple burst, {delta} (1-4 Hz)-ripple PAC occurred. The video showed that fluctuation of the diameter of these circles indicated the rhythmic changes during significant high values of {theta}-ripple PAC. ConclusionsWe inferred that ripple activities occurring during seizure evolution were modulated by {theta} rhythm. In addition, we concluded that rhythmic circles fluctuation presented in the video represents the PAC phenomenon. Our video is thus a useful tool for understanding how ripple activity is modulated by the low-frequency phase in relation with PAC.

neuroscience↗

bioRxiv2020

Motor and Sensory Cortical Processing of Neural Oscillatory Activities revealed by Human Swallowing using Intracranial Electrodes

Swallowing, a unique movement, is attributed to the indispensable orchestration of motor-output and sensory-input. We hypothesized that swallowing can illustrate differences between motor and sensory neural processing. Eight epileptic participants fitted with intracranial electrodes over the orofacial cortex were asked to swallow a water bolus. Mouth-opening and swallowing were treated as motor tasks, while water-injection as sensory tasks. Phase-amplitude coupling between lower frequency and high {gamma} (HG) band (75-150 Hz) was investigated. An (10-16 Hz) -HG coupling appeared before motor-related HG power increase (burst), and a {theta} (5-9 Hz) -HG coupling appeared during sensory-related HG burst. The motor- and sensory-related HG amplitude were modulated at the trough of oscillations and peak of {theta} oscillations, respectively. These contrasting results acquired from the orofacial cortex can help to fully elucidate the sensory-motor function in the brain.

neuroscience↗

bioRxiv2020

A meiosis-specific factor MRM/C19orf57 modulates localization of RAD51 and DMC1 recombinases to DSBs in mouse meiotic recombination

Meiotic recombination is critical for genetic exchange and generation of chiasmata that ensures faithful chromosome segregation during meiosis I. Meiotic recombination is initiated by DNA double-strand break (DSB) followed by multiple processes of DNA repair. The exact mechanisms how recombinases localize to DSB remained elusive. Here we show that C19orf57/4930432K21Rik/BRME1 is a new player for meiotic recombination in mice. C19orf57/4930432K21Rik/BRME1 associates with ssDNA binding proteins, BRCA2 and MEILB2/HSF2BP, critical recruiters of recombinases onto DSB sites. Disruption of C19orf57/4930432K21Rik/BRME1 shows severe impact on DSB repair and male fertility. Remarkably, removal of single stranded DNA (ssDNA) binding proteins from DSB sites is delayed, and reciprocally the loading of RAD51 and DMC1 onto resected ssDNA is impaired in Brme1 KO spermatocytes. We propose that C19orf57/4930432K21Rik/BRME1 modulates localization of recombinases to meiotic DSB sites through the interaction with the BRCA2-MEILB2/HSF2BP complex during meiotic recombination.

molecular biology↗

bioRxiv2019

Cortisol levels adter cold exposure are independent of adrenocorticotropic hormone stimulation

We previously showed that postmortem serum levels of adrenocorticotropic hormone (ACTH) were significantly higher in cases of hypothermia (cold exposure) than other causes of death. This study examined how the human hypothalamic-pituitary-adrenal axis, and specifically cortisol, responds to hypothermia.\n\nHuman samplesAutopsies on 205 subjects (147 men and 58 women; age 15-98 years, median 60 years) were performed within 3 days of death. Cause of death was classified as either hypothermia (cold exposure, n=14) or non-cold exposure (controls; n=191). Cortisol levels were determined in blood samples obtained from the left and right cardiac chambers and common iliac veins using a chemiluminescent enzyme immunoassay. Adrenal gland tissue samples were stained for cortisol using a rabbit anti-human polyclonal antibi.\n\nCell cultureAtT20, a mouse ACTH secretory cell line, and Y-1, a corticosterone secretory cell line derived from a mouse adrenal tumor, were analyzed in mono-and co-culture, and times courses of ACTH (in AtT20) and corticosterone (in Y-1) secretion were assessed after low temperature exposure mimicking hypothermia and compared with data for samples collected postmortem for other causes of death. However, no correlation between ACTH concentration and cortisol levels was observed in hypothermia cases. Immunohistologic analyses of samples from hypothermia cases showed that cortisol staining was localized primarily to the nucleus rather than the cytoplasm of cells in the zona fasciculata of the adrenal gland. During both mono-culture and co-culture, AtT20 cells secreted high levels of ACTH after 10-15 minutes of cold exposure, whereas corticosterone secretion by Y-1 cells increased slowly during the first 15-20 minutes of cold exposure. Similar to autopsy results, no correlation was detected between ACTH levels and corticosterone secretion, either in mono-culture or co-culture experiments. These results suggested that ACTH-independent cortisol secretion may function as a stress response during cold exposure.

biochemistry↗

bioRxiv2018

Proteomic analysis of RNA-dependent chromatin association of nuclear proteins

Various coding and non-coding transcripts are known to associate with chromatin and now there is accumulating evidence that interaction between RNA-binding proteins (RBPs) and RNA molecules regulate not only co-transcriptional mRNA processing, but also other biological processes within the nucleus. Although over a thousand of RBPs have been identified by several mass spectrometry-based methods, it is still unclear which of these RBPs actually associate with chromatin, especially through interaction with RNAs. In addition, biological outcomes of such RBP-RNA-chromatin interactions are yet to be elucidated.\n\nHere we describe a simple proteomics-based method for systematic screening of RBPs that are anchored to chromatin and/or insoluble nuclear substructures by RNA molecules. We used RNase A to release such RBPs from chromatin fraction and analyzed RNase A-solubilized proteins by mass spectrometry. Using this method, we were able to identify 156 RNase A-solubilized proteins of which 144 were known RBPs/RBP candidates. Interestingly, several key players of the non-homologous end-joining (NHEJ) pathway were enriched in RNase A-solubilized fraction and the RNA-mediated chromatin association of these factors appeared to be dependent on transcriptional elongation. Furthermore, some enzymes involved in metabolic pathways were also released from chromatin and/or an insoluble nuclear structure by RNase A treatment. In summary, our methodology is highly versatile and is potentially a useful tool to unravel new biological functions for RBP-RNA-chromatin interactions.

molecular biology↗

bioRxiv2018

High-quality SNPs from genic regions highlight introgression patterns among European white oaks (Quercus petraea and Q. robur).

The Src homology-2 domain containing phosphatase SHP2 is a critical regulator of signal transduction, being implicated in cell growth and differentiation. Activating mutations cause developmental disorders and act as oncogenic drivers in hematologic cancers. SHP2 is activated by phosphopeptide binding to the N-SH2 domain, triggering the release of N-SH2 from the catalytic PTP domain. Based on early crystallographic data, it has been widely accepted that opening of the binding cleft of N-SH2 serves as the key "allosteric switch" driving SHP2 activation. To test the putative coupling between binding cleft opening and SHP2 activation as assumed by the "allosteric switch" model, we critically reviewed structural data of SHP2 and we used extensive molecular dynamics (MD) simulation and free energy calculations of isolated N-SH2 in solution, SHP2 in solution, and SHP2 in a crystal environment. Our results demonstrate that the binding cleft in N-SH2 is constitutively flexible and open in solution, and that a closed cleft found in certain structures is a consequence of crystal contacts. The degree of opening of the binding cleft has only a negligible effect on the free energy of SHP2 activation. Instead, SHP2 activation is greatly favored by the opening of the central {beta}- sheet of N-SH2. We conclude that opening of the N-SH2 binding cleft is not the key allosteric switch triggering SHP2 activation. Significance StatementSHP2 is a multi-domain protein, playing an important role in up-regulating cellular processes such as cell survival, proliferation, and programmed cell death. SHP2 mutations cause developmental disorders and were found in many cancer types, including neuroblastoma, breast cancer, and leukemia. In healthy cells, SHP2 mainly takes an autoinhibited, inactive form, and SHP2 is activated upon binding of phosphopeptides to the N-SH2 domain. For the past two decades, the widening of the binding cleft upon peptide binding has been considered as the key event driving SHP2 activation. Here, by analyzing crystallographic data and molecular simulations, we demonstrate that the binding cleft in N-SH2 is, instead, already open and accessible in solution, and its degree of opening does not influence SHP2 activation.

evolutionary biology↗