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Hirose, S.

Publications and source records attributed to Hirose, S..

At least 19 recordsLinked to original sources

Microscopic collisions govern macroscopic aerotactic spreading through emergent transport coefficients

Collective migration is often attributed to complex cell-cell communication, yet coordinated multicellular dynamics can also emerge in organisms lacking social interactions. Continuum descriptions successfully capture such behaviors but generally rely on phenomenological transport coefficients whose microscopic origin remains elusive. Here we show that these coefficients emerge from cell-cell collisions and can be independently determined from experiments. We investigate the aerotactic dispersal of confined colonies of the solitary amoeba Acanthamoeba castellanii, in which oxygen consumption continuously reshapes the local environment to generate self-organized guidance cues. Combining quantitative videomicroscopy, oxygen mapping with phosphorescent sensing films, and oxygen-controlled microfluidics, we directly measure both the oxygen landscape and the aerotactic response governing colony expansion. We then develop a Patlak-Keller-Segel (PKS) -type drift-diffusion model whose transport coefficients are entirely determined from independent experiments and microscopic-to-macroscopic modeling approach, without adjustable parameters. The model quantitatively reproduces the observed dynamics, including the coexistence of a fast ballistic front and a trailing transient accumulation band. We show that both diffusion and aerotactic transport are modulated by the same collision-controlled mechanism through density-dependent changes in cell persistence. More generally, our results establish transport coefficients as measurable emergent properties bridging microscopic cell dynamics and macroscopic collective behavior, providing a predictive framework for oxygen-guided migration in living active matter.

biophysics↗

Pre-movement neural population activity in human motor cortex reflects the subsequent outcome of futsal free kicks

Brain states immediately before movement may shape skilled athletic performance, but translating electroencephalography (EEG)-based monitoring to sport has been limited by dense montages and laboratory-constrained tasks. We asked whether a portable three-channel EEG system can detect outcome-related preparatory activity during a realistic futsal free-kick task. EEG from C3, Cz, and C4 during the 2 s before each kick was used to decode successful versus unsuccessful trials with channel-wise linear support vector machines (SVMs), and the same approach was tested for transfer across recording days. To relate decoding to interpretable physiology, alpha- and beta-band power were also compared between outcomes. Successful and failed kicks were decoded significantly above label-shuffled null distributions within recording days across all channels, showing that low-density EEG can capture sensor-level information linked to subsequent performance. However, decoding did not generalize reliably across days, indicating that these neural signatures were session specific. Spectral analysis showed selectively increased C3 beta-band power before successful kicks, whereas alpha-band power showed no significant outcome-related differences. These findings support portable EEG as a practical route toward monitoring preparatory brain states in sport, while suggesting that real-world use will require short day-specific calibration or adaptive decoding.

bioengineering↗

Population genomic scan of endogenous retrovirus insertions revealed cryptic drivers of selective sweep in wild house mouse genomes

Endogenous retroviruses (ERVs) represent a major source of structural variation in mammalian genomes, yet their diversity in wild populations remains poorly understood. Here, we conduct a comprehensive genome-wide survey of non-reference ERV insertions in wild house mice (Mus musculus) to characterize their distribution and evolutionary dynamics. Using a newly developed bioinformatics pipeline, we detected and annotated over 100,000 non-reference ERV insertions from short-read sequencing data across 163 wild mouse genomes. Our analyses revealed marked differences in ERV insertion patterns among subspecies and populations, including variation in genomic localization and population-specific polymorphisms. These heterogeneous patterns suggest distinct evolutionary histories and host-retrovirus interactions across populations. For instance, we describe the distribution of the ERV-derived Fv4 locus, which shows subspecies-restricted occurrence and confers resistance to murine leukemia viruses (MLVs). Several lines of evidence showed that the spread of Fv4 insertions in Korean population has been driven by adaptive introgression from neighboring populations. Our study provides the first large-scale population genomic scan of ERV diversity in wild house mice. By cataloguing extensive polymorphism in non-reference ERV insertions, our results highlight the role of ERVs as dynamic genomic elements that contribute to structural variation and adaptive evolution. Article SummaryEndogenous retroviruses (ERVs) are viral sequences embedded in animal genomes that can create structural genetic variation. In this study, we conducted a genome-wide survey of non-reference ERV insertions in 163 wild house mice using short-read sequencing data and a newly developed computational pipeline. We identified more than 100,000 polymorphic ERV insertions and found substantial differences among subspecies and geographic populations. One example, the ERV-derived Fv4 locus, illustrates how ERV variation can influence the genetic pattern of polymorphisms in the species. These results demonstrate that ERVs are dynamic genomic elements that contribute to population divergence and adaptive evolution.

evolutionary biology↗

Dictyostelium discoideum chemotaxis is altered by hypoxia to orient streaming toward higher oxygen level independently of aerotaxis.

BackgroundDictyostelium discoideum (Dd) exhibits a unique life cycle marked by its transition from single-cell amoeboid movement to multicellular development in response to environmental stimuli. While its chemotactic response to cyclic adenosine monophosphate (cAMP) has been extensively studied, experiments are usually carried out in a high oxygen environment (21% O2, also called normoxia) that might not reflect the natural condition for a soil amoeba as hypoxia is common underground. Our recent research has unveiled a novel phenomenon termed aerotaxis, wherein Dd cells migrate towards oxygen-rich environments under low oxygen (hypoxia). ResultsWe tested Dd response when submitted to two different stress sources: starvation and hypoxia. While both stresses induce a motile response, namely chemotaxis and aerotaxis, we were able to decoupled both type of responses to explore potential shared mechanisms. Importantly, aerotaxis appears to be operated independently of known chemotactic pathways, demonstrating unique signaling pathways and cellular responses. Aerotaxis contributes to Dd developmental processes by letting cells escape from acute hypoxia. Even though chemotactic response can occur at less than 2% O2, it does not lead to well organized or stable streaming. Furthermore, in an oxygen gradient, aggregation center for chemotactic response appears preferentially at higher O2 level. RT-qPCR analysis show that hypoxia only slightly reduces the expression of genes required for chemotactic response, suggesting that the bias toward high O2 might occur at another level. Reoxygenation of cells that have been starved in hypoxic condition for 18h allow rapid aggregation but require de novo protein synthesis. ConclusionAerotaxis and chemotaxis mechanisms do not interact directly. However, when cells are exposed to both hypoxia and starvation, both mechanisms can be combined to direct the migration of cells toward place with higher oxygen level. As hypoxia is frequent in the soil where Dd usually grow, formation of aggregation centers at, or close to the soil surface, where oxygen is abundant, will be advantageous. Low O2 level does not preclude cells to participate to streaming but seems to reduce or delay their ability to produce stable aggregation centers, resulting into bias favoring centers that form at higher oxygen level.

cell biology↗

Polyploidy of MDA-MB-231 cells drives increased extravasation with enhanced cell-matrix adhesion

Metastasis, the leading cause of cancer-related deaths, involves a complex cascade of events, including extravasation. Despite extensive research into metastasis, the mechanisms underlying extravasation remain unclear. Molecular targeted therapies have advanced cancer treatment, yet their efficacy is limited, prompting exploration into novel therapeutic targets. Here, we showed the association of polyploidy in MDA-MB-231 breast cancer cells and their extravasation, using microfluidic systems to reproduce the in vivo microvascular environment. We observed enhanced extravasation in polyploid cells alongside upregulated expression of genes involved in cell-substrate adhesion and cell mechanical dynamics. These findings offer insights into the relationship between polyploidy and extravasation, highlighting potential targets for cancer therapy.

bioengineering↗

Theoretical analyses for the evolution of biogenic volatile organic compounds (BVOCs) emission strategy

Plants emit biogenic volatile organic compounds (BVOCs) as signaling molecules, playing a crucial role in inducing resistance against herbivores. Neighboring plants that eavesdrop on BVOC signals can also increase defenses against herbivores or alter growth patterns to respond to potential risks of herbivore damage. Despite the significance of BVOC emissions, the evolutionary rationales behind their release and the factors contributing to the diversity in such emissions remain poorly understood. To unravel the conditions for the evolution of BVOC emission, we developed a spatially-explicit model that formalizes the evolutionary dynamics of BVOC emission and non-emission strategies. Our model considered two effects of BVOC signaling that impact the fitness of plants: intra-individual communication, which mitigates herbivore damage through the plants own BVOC signaling incurring emission costs, and inter-individual communication, which alters the influence of herbivory based on BVOC signals from other individuals without incurring emission costs. Employing two mathematical models--the lattice model and the random distribution model--we investigated how intra-individual communication, inter-individual communication, and spatial structure influenced the evolution of BVOC emission strategies. Our analysis revealed that the increase in intra-individual communication promotes the evolution of the BVOC emission strategy. In contrast, the increase in inter-individual communication effect favors cheaters who benefit from the BVOCs released from neighboring plants without bearing the costs associated with BVOC emission. Our analysis also demonstrated that the narrower the spatial scale of BVOC signaling, the higher the likelihood of BVOC evolution. This research sheds light on the intricate dynamics governing the evolution of BVOC emissions and their implications for plant-plant communication.

evolutionary biology↗

Role of the right middle occipital gyrus in egocentric spatial orientation in reference to gravitational information: Evidence from a pre-registered rTMS study

Accurate perception of the orientation of external objects relative to the body, known as egocentric spatial orientation, is fundamental to action. Previously, we found via behavioral and magnetic resonance imaging voxel-based morphometry studies that egocentric spatial orientation is distorted when the whole body is tilted with respect to gravity, and that the magnitude of this perceptual distortion is correlated with grey matter volume in the right middle occipital gyrus (rMOG). In the present pre-registered study, we demonstrated that neural processing in the rMOG is indeed a cause of the perceptual distortion. We transiently suppressed neural activity in the rMOG by applying low-frequency repetitive transcranial magnetic stimulation (rTMS) and evaluated the consequent effect on perceptual distortion. Our results showed that while rTMS over the rMOG significantly reduced perceptual distortion when the body was tilted with respect to gravity, it did not affect egocentric spatial orientation when in the upright position. No changes in perceptual distortion were observed when rTMS was applied to a control site (right temporoparietal junction) or to air (sham TMS). These results indicate that neural processing in the rMOG during body tilt is an essential cause of perceptual distortion, suggesting that the rMOG is engaged in egocentric spatial orientation concerning gravitational information. Significance statementThe findings of this pre-registered study support a causal role of neural activity in the right middle occipital gyrus (rMOG) in the perceptual distortion of egocentric spatial orientation induced by whole-body tilt relative to gravity. We suppressed neural activity in the rMOG using low-frequency repetitive transcranial magnetic stimulation (rTMS) and measured perceptual distortion. We observed a significant reduction in perceptual distortion after rTMS over the rMOG, but not after control or sham rTMS. These results provide, for the first time, direct evidence of the engagement of the rMOG in egocentric spatial orientation in reference to gravitational information.

neuroscience↗

Hyper-adaptation in the Human Brain: Functional and structural changes in the foot section of the primary motor cortex in a top wheelchair racing Paralympian

The human brain has the capacity to drastically alter its somatotopic representations in response to congenital or acquired limb deficiencies and dysfunctions. The main purpose of the present study was to elucidate such extreme adaptability in the brain of an active top wheelchair racing Paralympian (participant P1) who has congenital paraplegia (dysfunction of bilateral lower limbs). Participant P1 has undergone long-term wheelchair racing training using bilateral upper limbs and has won a total of 19 medals in six consecutive summer Paralympic games as of 2021. We examined the functional and structural changes in the foot section of the primary motor cortex (M1) in participant P1 as compared to able-bodied control participants. We also examined the functional and structural changes in three other individuals (participants P2, P3, and P4) with acquired paraplegia, who also had long-term non-use period of the lower limbs and had undergone long-term training for wheelchair sports (but not top athletes at the level of participant P1). We measured brain activity in all the participants using functional magnetic resonance imaging (MRI) when bimanual wrist extension-flexion movement was performed, and the structural MRI images were collected. Compared to 37 control participants, participant P1 showed significantly greater activity in the M1 foot section during the bimanual task, and significant local GM expansion in this section. Significantly greater activity in the M1 foot section was also observed in participant P4, but not in P2 and P3, and the significant local GM expansion was observed in participant P2, but not in P3 and P4. Thus, functional or structural change was observed in an acquired paraplegic participant, but was not observed in all the paraplegic participants. The functional and structural changes typically observed in participant P1 may represent extreme adaptability of the human brain. We discuss the results in terms of a new idea of hyper-adaptation.

neuroscience↗

CUX2 mutations in temporal lobe epilepsy; increased kainate susceptibility and excitatory input to hippocampus in deficient mice

CUX2 gene encodes a transcription factor that controls neuronal proliferation, dendrite branching and synapse formation, locating at the epilepsy-associated chromosomal region 12q24 that we previously identified by a genome-wide association study (GWAS) in Japanese population. A CUX2 recurrent de novo variant p.E590K has been described in patients with rare epileptic encephalopathies and the gene is a candidate for the locus, however the mutation may not be enough to generate the genome-wide significance in the GWAS and whether CUX2 variants appear in other types of epilepsies and physiopathological mechanisms are remained to be investigated. Here in this study, we conducted targeted sequencings of CUX2, a paralog CUX1 and its short isoform CASP harboring a unique C-terminus on 271 Japanese patients with a variety of epilepsies, and found that multiple CUX2 missense variants, other than the p.E590K, and some CASP variants including a deletion, predominantly appeared in patients with temporal lobe epilepsy (TLE). The CUX2 variants showed abnormal localization in human cell culture analysis. While wild-type CUX2 enhances dendritic arborization in fly neurons, the effect was compromised by some of the variants. Cux2- and Casp-specific knockout mice both showed high susceptibility to kainate, increased excitatory cell number in the entorhinal cortex, and significant enhancement in glutamatergic synaptic transmission to the hippocampus. CASP and CUX2 proteins physiologically bound to each other and co-expressed in excitatory neurons in brain regions including the entorhinal cortex. These results suggest that CUX2 and CASP variants contribute to the TLE pathology through a facilitation of excitatory synaptic transmission from entorhinal cortex to hippocampus.

neuroscience↗

Transcranial magnetic stimulation of the occipital cortex interferes with foot movements in blind individuals

Research has shown that the occipital cortex can be reorganized and repurposed for nonvisual perception and cognitive functions following visual loss in blind individuals. However, no studies have directly examined the involvement of the visual cortex in motor function. Here, we show that a rhythmic foot movement performed by acquired blind individuals can be disrupted by transcranial magnetic stimulation (TMS) to their primary and secondary visual cortex (V1/V2). This disruptive effect was absent for congenitally blind or sighted individuals. As a control, TMS to the neck muscles of acquired blind individuals confirms that this disruptive effect was not caused solely by the sensory (tactile/auditory) sensations accompanying the stimulation. Our results provide the direct evidence that functional repurposing of the human visual cortex is not restricted to perception and cognitive functions but also extends to motor function. Moreover, our findings suggest the nessecity of the visual experience before visual loss for the functional reorganization of the visual cortex for motor function. Significance statementThe brain can adapt remarkably after sensory loss. One striking example is that after visual loss, the visual cortex--deprived of visual input--is often reused for nonvisual perception and higher cognition. Here, we show that it can also support motor control. Using transcranial magnetic stimulation, we transiently disrupted processing in the visual cortex while participants performed rhythmic foot movements. This disruption impaired performance in people who became blind after birth, but not in sighted individuals or those blind from birth. These findings demonstrate that the visual cortex can take on a motor function after vision is lost, but only with prior visual experience.

neuroscience↗

Transcriptional milestones in Dictyostelium development

Development of the social amoeba Dictyostelium discoideum begins by starvation of single cells and ends in multicellular fruiting bodies 24 hours later. These major morphological changes are accompanied by sweeping gene expression changes, encompassing nearly half of the 13,000 genes in the genome. To explore the relationships between the transcriptome and developmental morphogenesis, we performed time-series RNA-sequencing analysis of the wild type and 20 mutant strains with altered morphogenesis. These strains exhibit arrest at different developmental stages, accelerated development, or terminal morphologies that are not typically seen in the wild type. Considering eight major morphological transitions, we identified 1,371 milestone genes whose expression changes sharply between two consecutive transitions. We also identified 1,099 genes as members of 21 regulons, which are groups of genes that remain coordinately regulated despite the genetic, temporal, and developmental perturbations in the dataset. The gene annotations in these milestones and regulons validate known transitions and reveal several new physiological and functional transitions during development. For example, we found that DNA replication genes are co-regulated with cell division genes, so they are co-expressed in mid-development even though chromosomal DNA is not replicated at that time. Altogether, the dataset includes 486 transcriptional profiles, across developmental and genetic conditions, that can be used to identify new relationships between gene expression and developmental processes and to improve gene annotations. We demonstrate the utility of this resource by showing that the cycles of aggregation and disaggregation observed in allorecognition-defective mutants involve a dedifferentiation process. We also show unexpected variability and sensitivity to genetic background and developmental conditions in two commonly used genes, act6 and act15, and robustness of the coaA gene. Finally, we propose that gpdA should be used as a standard for mRNA quantitation because it is less sensitive to genetic background and developmental conditions than commonly used standards. The dataset is available for democratized exploration without the need for programming skills through the web application dictyExpress and the data mining environment Orange.

genomics↗

Bimanual digit training improves right-hand dexterity in older adults by reactivating declined ipsilateral motor-cortical inhibition

Improving deteriorated sensorimotor functions in older individuals is a social necessity in a super-aging society. Previous studies suggested that the declined interhemispheric sensorimotor inhibition observed in older adults is associated with their deteriorated hand/finger dexterity. Here, we examined whether bimanual digit exercises, which can train the interhemispheric inhibitory system, improve deteriorated hand/finger dexterity in older adults. Forty-eight healthy, right-handed, older adults (65-78 years old) were divided into two groups, i.e., the bimanual (BM) digit training and right-hand (RH) training groups, and intensive daily training was performed for 2 months. Before and after the training, we evaluated individual right hand/finger dexterity using a peg task, and the individual state of interhemispheric sensorimotor inhibition by analyzing ipsilateral sensorimotor deactivation via functional magnetic resonance imaging when participants experienced a kinesthetic illusory movement of the right-hand without performing any motor tasks. Before training, the degree of reduction/loss of ipsilateral motor-cortical deactivation was associated with dexterity deterioration. After training, the dexterity improved only in the BM group, and the dexterity improvement was correlated with reduction in ipsilateral motor-cortical activity. The capability of the brain to inhibit ipsilateral motor-cortical activity during a simple right-hand sensory-motor task is tightly related to right-hand dexterity in older adults.

neuroscience↗

Astrocyte Ca2+ Signaling is Facilitated in an Scn1a+/- Mouse Model of Dravet Syndrome

Dravet syndrome (DS) is an infantile-onset epileptic encephalopathy. More than 80% of DS patients have a heterozygous mutation in SCN1A, which encodes a subunit of the voltage-gated sodium channel, Nav1.1, in neurons. The roles played by astrocytes, the most abundant glial cell type in the brain, have been investigated in the pathogenesis of epilepsy; however, the specific involvement of astrocytes in DS has not been clarified. In this study, we evaluated Ca2+ signaling in astrocytes using genetically modified mice that have a loss-of-function mutation in Scn1a. We found that the slope of spontaneous Ca2+ spiking was increased without a change in amplitude in Scn1a+/- astrocytes. In addition, ATP-induced transient Ca2+ influx and the slope of Ca2+ spiking were also increased in Scn1a+/- astrocytes. These data indicate that perturbed Ca2+ dynamics in astrocytes may be involved in the pathogenesis of DS.

neuroscience↗

The excitatory/inhibitory balance of synaptic transmission is impaired at higher extracellular Ca2+ concentrations in Scn1a+/- mouse model of Dravet syndrome

Dravet syndrome (DS) is an intractable form of childhood epilepsy that occurs in infancy. More than 80% of all patients have a heterozygous abnormality in the SCN1A gene, which encodes a subunit of Na+ channels in the brain. However, the detailed pathogenesis of DS remains unclear. This study investigated the synaptic pathogenesis of this disease in terms of excitatory/inhibitory balance using a mouse model of DS. We show that excitatory postsynaptic currents were similar between Scn1a knock-in neurons (Scn1a+/- neurons) and wild-type neurons, but inhibitory postsynaptic currents were significantly lower in Scn1a+/- neurons. Moreover, both the vesicular release probability and the number of inhibitory synapses were significantly lower in Scn1a+/- neurons compared with wild-type neurons. There was no proportional increase in inhibitory postsynaptic current amplitude in response to increased extracellular Ca2+ concentrations. Our study revealed that the number of inhibitory synapses is significantly reduced in Scn1a+/- neurons, while the sensitivity of inhibitory synapses to extracellular Ca2+ concentrations is markedly increased. These data suggest that Ca2+ tethering in inhibitory nerve terminals may be disturbed following the synaptic burst, likely leading to epileptic symptoms.

neuroscience↗

Catalytic Promiscuity of Rice 2-Oxoglutarate/Fe(II)-Dependent Dioxygenases Supports Xenobiotic Metabolism

The rice 2-oxoglutarate/Fe(II)-dependent dioxygenase HIS1 mediates the catalytic inactivation of five distinct {beta}-triketone herbicides (bTHs). During a search for potential inhibitors of HIS1, we found that it mediates the hydroxylation of trinexapac-ethyl (TE) in the presence of Fe2+ and 2-oxoglutarate. TE is a plant growth regulator that blocks gibberellin biosynthesis, and we observed that its addition to culture medium induced growth retardation of rice seedlings in a concentration-dependent manner. Similar treatment with hydroxylated TE revealed that hydroxylation greatly attenuated the inhibitory effect of TE on plant growth. Forced expression of HIS1 in a rice his1 mutant also reduced its sensitivity to TE compared with that of the nontransformant. These results indicated that HIS1 metabolizes TE and thereby markedly reduces its ability to slow plant growth. Furthermore, testing of five HIS1-related proteins (HSLs) of rice revealed that OsHSL2 and OsHSL4 also metabolize TE in vitro. HSLs from wheat and barley also showed such activity. In contrast, OsHSL1, which shares the highest amino acid sequence identity with HIS1 and metabolizes the bTH tefuryltrione, did not manifest TE-metabolizing activity. Site-directed mutagenesis of OsHSL1 informed by structural models showed that substitution of three amino acids with the corresponding residues of HIS1 conferred TE-metabolizing activity similar to that of HIS1. Our results thus reveal a catalytic promiscuity of HIS1 and its related enzymes that supports xenobiotic metabolism in plants. One-sentence summaryThe rice 2-oxoglutarate/Fe(II)-dependent dioxygenase HIS1 and related enzymes show broad substrate specificity and mediate metabolism of the growth regulator trinexapac-ethyl as well as of herbicides.

plant biology↗

Hypoxia triggers collective aerotactic migration in Dictyostelium discoideum

It is well known that eukaryotic cells can sense oxygen (O2) and adapt their metabolism accordingly. It is less known that they can also move towards regions of higher oxygen level (aerotaxis). Using a self-generated hypoxic assay, we show that the social amoeba Dictyostelium discoideum displays a spectacular aerotactic behavior. When a cell colony is covered by a coverglass, cells quickly consume the available O2 and the ones close to the periphery move directionally outward forming a dense ring keeping a constant speed and density. To confirm that O2 is the main molecular player in this seemingly collective process, we combined two technological developments, porphyrin based O2 sensing films and microfluidic O2 gradient generators. We showed that Dictyostelium cells exhibit aerotactic and aerokinetic (increased speed at low O2) response in an extremely low range of O2 concentration (0-1.5%) indicative of a very efficient detection mechanism. The various cell behaviors under self-generated or imposed O2 gradients were modeled with a very satisfactory quantitative agreement using an in silico cellular Potts model built on experimental observations. This computational model was complemented with a parsimonious Go or Grow partial differential equation (PDE) model. In both models, we found that the collective migration of a dense ring can be explained by the interplay between cell division and the modulation of aerotaxis, without the need for cell-cell communication.

biophysics↗

Valid and powerful statistical test for decoding accuracy-proposal of Permutation-based Information Prevalence Inference using the i-th order statistic

In fMRI decoding studies using pattern classification, a "second-level" group statistical test is typically performed after "first-level" decoding analyses for individual participants. Neuroscientists often test the mean decoding accuracy across participants against the chance-level accuracy (e.g., one-sample Student t-test) to verify whether brain activation includes information about the label (i.e., cognitive content). However, Allefeld et al., (2016) notified that positive results for such tests only indicate that "there are some people in the population whose fMRI data carry information about the experimental condition." Thus, such tests cannot provide inferences about the trend of the majority. They proposed an alternative method, in which prevalence inference is implemented. In this study, I extended their method and propose statistical test "information prevalence inference using the i-th order statistic (i-test)". Compared with the method proposed in the previous study, i-test has high statistical power to provide an inference regarding major population trends. In i-test, the i-th lowest sample decoding accuracy (the i-th order statistic) is compared to the null distribution to test whether the proportion of the higher-than-chance decoding accuracy in the population (information prevalence) is higher than the threshold. Thus, a significant result of the i-test can be interpreted as "the majority of the population has information about the label in the brain." Numerical calculation identified its high statistical power. Also, theoretical detail is provided, and the use of this method in an fMRI decoding study is demonstrated. Allefeld, C., Gorgen, K., Haynes, J.D., 2016. Valid population inference for information-based imaging: From the second-level t-test to prevalence inference. Neuroimage.

neuroscience↗

A stochastic epigenetic switch controls the dynamics of T-cell lineage commitment

Cell fate decisions occur through the switch-like, irreversible activation of fate-specifying genes. These activation events are often assumed to be tightly-coupled to changes in upstream transcription factors, but could also be constrained by cis-epigenetic mechanisms at individual gene loci. Here, we studied the activation of Bcl11b, which controls T-cell fate commitment. To disentangle cis and trans effects, we generated mice where two Bcl11b copies are tagged with distinguishable fluorescent proteins. Quantitative live microscopy of progenitors from these mice revealed that Bcl11b turned on after a stochastic delay averaging multiple days, which varied not only between cells but also between Bcl11b alleles within the same cell. Genetic perturbations, together with mathematical modeling, showed that a distal enhancer controls the rate of epigenetic activation, while a parallel Notch-dependent trans-acting step stimulates expression from activated loci. These results show that developmental fate transitions can be controlled by stochastic cis-acting events on individual loci.

bioinformatics↗