Biology subjects

Thompson, W. F.

Publications and source records attributed to Thompson, W. F..

5 recordsLinked to original sources

bioRxiv2025

Replication Timing Uncovers a Two-Compartment Nuclear Architecture of Interphase Euchromatin in Maize

Genome replication is temporally regulated during S phase, with specific genomic regions replicating at defined times in a process that is known as replication timing (RT). Based on 3D cytology in replicating nuclei, we previously proposed a "mini-domain chromatin fiber RT model" for maize euchromatin that suggested it is subdivided into early-S and middle-S compartments distinguished by chromatin condensation and RT. However, whether this compartmentalization reflects a general nuclear architecture that persists throughout the cell cycle was unclear. To test this model, we conducted two orthogonal assays - Hi-C for genome-wide interaction data and 3D FISH for direct visualization of chromatin organization. Hi-C eigenvalues and insulation scores revealed distinct patterns of early-S regions having negative insulation scores with long-range contacts while middle-S regions showed the opposite. Early-S regions correlated more strongly with epigenomic signatures of open, transcriptionally active chromatin than middle-S regions. 3D oligo FISH painting confirmed that early-S and middle-S regions occupy adjacent but largely non-overlapping nucleoplasmic spaces during all interphase stages, including G1. Our findings redefine the maize euchromatin "A" compartment as having two distinct, closely interspersed subcompartments, early-S and middle-S, underscoring the importance of replication timing (RT) as a defining feature of chromatin architecture and genome organization.

genetics↗

bioRxiv2020

Three distinct neural mechanisms support movement-induced analgesia

Pain is essential for our survival by protecting us from severe injuries. Pain signals may be exacerbated by continued physical activities but can also be interrupted or over-ridden by physical movements, a process called movement-induced analgesia. A number of neural mechanisms have been proposed to account for this effect, including the reafference principle, the gate control theory of pain, and the top-down psychological modulation. Given that the analgesic effects of these mechanisms are temporally overlapping, it is unclear whether movement-induced analgesia results from a single neural mechanism or the joint action of multiple neural mechanisms. To address this question, we conducted five experiments on 130 healthy human subjects. First, the frequency of hand shaking was manipulated in order to quantify the relationship between the strength of the voluntary movement and the analgesic effect. Second, the temporal delay (between hand shaking and nociceptive laser stimuli) and the stimulated side (nociceptive laser stimuli were delivered on the hand ipsilateral or contralateral to the shaken one) were manipulated to quantify the temporal and spatial characteristics of the analgesic effect induced by voluntary movement. Combining psychophysics and electroencephalographic recordings, we demonstrated that movement-induced analgesia is a result of the joint action of multiple neural mechanisms. This investigation is the first to disentangle the distinct contributions of different neural mechanisms to the analgesic effect of voluntary movement. These findings extend our understanding of sensory attenuation arising from voluntary movement and may prove instrumental in the development of new strategies in pain management.

neuroscience↗

bioRxiv2020

Comparing DNA replication programs reveals large timing shifts at centromeres of endocycling cells in maize roots

Plant cells undergo two types of cell cycles - the mitotic cycle in which DNA replication is coupled to mitosis, and the endocycle in which DNA replication occurs in the absence of cell division. To investigate DNA replication programs in these two types of cell cycles, we pulse labeled intact root tips of maize (Zea mays) with 5-ethynyl-2-deoxyuridine (EdU) and used flow sorting of nuclei to examine DNA replication timing (RT) during the transition from a mitotic cycle to an endocycle. Here, we compare sequence-based RT profiles and found that most regions of the maize genome replicate at the same time during S phase in mitotic and endocycling cells, despite the need to replicate twice as much DNA in the endocycle. However, regions collectively corresponding to 2% of the genome displayed significant changes in timing between the two types of cell cycles. The majority of these regions are small, with a median size of 135 kb, and shift to a later RT in the endocycle. However, we found larger regions that shifted RT in centromeres of seven of the ten maize chromosomes. These regions covered the majority of the previously defined functional centromere in each case, which are [~]1-2 Mb in size in the reference genome. They replicate mainly during mid S phase in mitotic cells, but primarily in late S phase of the endocycle. Strikingly, the immediately adjacent pericentromere sequences are primarily late replicating in both cell cycles. Analysis of CENH3 enrichment levels in nuclei of different ploidies suggested that there is only a partial replacement of CENH3 nucleosomes after endocycle replication is complete. The shift to later replication of centromeres and reduced CENH3 enrichment after endocycle replication is consistent with the hypothesis that centromeres are being inactivated as their function is no longer needed. AUTHOR SUMMARYIn traditional cell division, or mitosis, a cells genetic material is duplicated and then split between two daughter cells. In contrast, in some specialized cell types, the DNA is duplicated a second time without an intervening division step, resulting in cells that carry twice as much DNA - a phenomenon called an endocycle, which is common during plant development. At each step, DNA replication follows an ordered program, in which highly compacted DNA is unraveled and replicated in sections at different times during the synthesis (S) phase. In plants, it is unclear whether traditional and endocycle programs are the same. Using root tips of maize, we found a small portion of the genome whose replication in the endocycle is shifted in time, usually to later in S phase. Some of these regions are scattered around the genome, and mostly coincide with active genes. However, the most prominent shifts occur in centromeres. This location is noteworthy because centromeres orchestrate the process of separating duplicated chromosomes into daughter cells, a function that is not needed in the endocycle. Our observation that centromeres replicate later in the endocycle suggests there is an important link between the time of replication and the function of centromeres.

genomics↗

bioRxiv2018

The dynamic emergence of musical pitch structure in human cortex

Tonal music the world over is characterized by a hierarchical structuring of pitch, whereby certain tones appear stable and others unstable within their musical context. Despite its prevalence, the cortical mechanisms supporting such a percept remain poorly understood. The current study probed the neural processing dynamics underlying the representation of pitch in Western Tonal Music. Listeners were presented with tones comprising all twelve pitch-classes embedded within a musical context whilst having their magnetoencephalographic (MEG) activity recorded. Using multivariate pattern analysis (MVPA), decoders attempted to classify the identity of tones from their corresponding MEG activity at each peristimulus time sample, providing a dynamic measure of their cortical dissimilarity. Time-evolving dissimilarities between tones were then compared with the predictions of several acoustic and perceptual models. Following tone onset, we observed a temporal evolution in the brains representation. Dissimilarities between tones initially reflected their fundamental frequency separation, but beyond 200 ms reflected their status within the tonal hierarchy of perceived stability. Furthermore, when the dissimilarities corresponding to this latter period were transposed into different keys, cortical relations between keys correlated with the well-known circle of fifths. Convergent with fundamental principles of music-theory and perception, current results detail the dynamics with which the complex perceptual structure of Western tonal music emerges in human cortex within the timescale of an individual tone.\n\nSignificance statementIn music, pitch is organized along a hierarchy of perceived stability. Applying stimulus decoding techniques to the Magnetoencephalographic activity of subjects during music-listening, we examined the structure of this hierarchy in cortex and the dynamics with which it emerges at the timescale of an individual tone. Following its onset, we observed a temporal evolution in the brains representation of a tone. Activity initially reflected its pitch-value (fundamental frequency) before reflecting its status within the tonal hierarchy of perceived stability. Transposing this later period of activity into different musical keys, we found that inter-key distances reflected the well-known circle of fifths. Our results provide a link between the complex perceptual structure of tonal music and its dynamic emergence in cortex.

neuroscience↗

bioRxiv2016

Repliscan: a tool for classifying replication timing regions

BackgroundReplication timing experiments that use label incorporation and high throughput sequencing produce peaked data similar to ChIP-Seq experiments. However, the differences in experimental design, coverage density, and possible results make traditional ChIP-Seq analysis methods inappropriate for use with replicating timing.\n\nResultsTo accurately detect and classify regions of replication across the genome, we present Repliscan. Repliscan robustly normalizes, automatically removes outlying and uninformative data points, and classifies Repli-seq signals into discrete combinations of replication signatures. The quality control steps and self-fitting methods makes Repliscan generally applicable and superior to previous methods with thresholds inapplicable to different genomes.\n\nConclusionsRepliscan is simple and effective to use on organisms with different magnitude genome sizes and sequencing coverage as low as 2.4x.

bioinformatics↗