Biology subjects

Boyd, M.

Publications and source records attributed to Boyd, M..

9 recordsLinked to original sources

bioRxiv2026

Mechanical Checkpoint for Cell Division in Three-Dimensional Microenvironments

Cell division within mechanically confining extracellular matrices (ECMs) is a key regulator of tissue morphogenesis and cancer progression. Although the intracellular force-generation mechanisms that drive volumetric growth and mitotic elongation are well characterized, how ECMs resist these forces remains poorly understood. Unlike linearly elastic materials, fibrillar ECMs exhibit nonlinear and viscoelastic behaviors that fundamentally alter how they oppose cell-generated stresses. Using a fiber-level computational model, we dissected the origins of ECM-mediated mechanical confinement during mitosis. We identified three distinct modes of resistance: compressive resistance at the cell poles, shear resistance from a pericellular shell, and tensile resistance at the cell equator. The relative contributions of these modes depended on fiber architecture and connectivity; however, shear resistance from the pericellular shell--pre-tensed by volumetric growth during G1--consistently dominated as the primary mechanical barrier to mitotic elongation. These findings suggest that the pericellular shell functions as a natural mechanical checkpoint on cell division within collagen-rich microenvironments. Notably, a finite element continuum model, despite being the most widely used framework for tissue mechanics, failed to reproduce these behaviors, underscoring the necessity of fiber-resolution approaches. We propose that overcoming this mechanical checkpoint is a critical step in cancer progression, enabling cells to divide within the dense stromal matrices characteristic of metastatic tumors.

biophysics↗

bioRxiv2026

The not-so-great speciator: Systematics and species limits in a rapid radiation, the Asiatic white-eye complex (Zosterops spp.)

Abstract/SummaryHere we untangle the systematics of the Asiatic white-eye complex (Zosterops spp.) to better understand the early stages of a recent island radiation. We adopt an integrative approach involving allelic data, genome-scale single nucleotide polymorphisms (SNPs), and museum-based morphometrics coupled with a comprehensive sampling to provide the most holistic understanding of the group to date. The island lineages of Asiatic white-eyes across Indonesia, the Philippines, East Asia, the adjacent oceanic islands of the Western Pacific underwent a deep split separating Zosterops everetti and Z. nigrorum in the Phillippines from a very rapid radiation including Z. japonicus, Z. meyeni, and Z. montanus in the Philippines, Japan, and Indonesia. Z. nigrorum catarmanensis on Camiguin South in the Philippines was found to be nested within Z. montanus and a species limit between Z. nigrorum populations on Panay and Luzon was strongly supported. Phylogenetic splits and population structure were detected within the clade containing Z. japonicus, Z. meyeni, and Z. montanus. A well-supported split separates a northern group including Northern Philippines Z. montanus subspecies, Z. meyeni, and Z. japonicus from the southerly Z. montanus taxa. This creates a paraphyletic Z. montanus. However, based on speciation rates within the broader Asiatic white-eye clade this break likely does not yet represent evolutionarily independent species lineages. Morphological evolution is taking place within the Asiatic white-eyes especially within the robust, large-billed subspecies of Z. japonicus on the oceanic islands of Japan and in the newly identified yellow-morph of Z. montanus on Camiguin South.

evolutionary biology↗

bioRxiv2025

Population coupling of V1 and V4 neurons and its relation to local cortical state fluctuations and attention in macaque monkey

Neurons couple to various degrees to the activity level of the local neighboring population whereby strongly coupled choristers and weakly coupled soloists have been identified as two extremes of a continuous spectrum. At the same time neuronal populations undergo coordinated ON and OFF cortical state activity fluctuations, which are locally modulated by attention. The population coupling of soloists and choristers suggests that soloists should show limited alignment with cortical state fluctuations, while choristers should exhibit profound alignment. To test this, we recorded neurons across cortical layers in macaque areas V1 and V4, while animals performed a feature based spatial attention task. As expected, we found a wide range of population coupling strength of neurons. In line with our prediction, coupling of choristers to cortical state changes (ON-OFF transitions) was generally stronger than that of soloists. The strength of population coupling of neurons was similar during spontaneous and stimulus driven activity. Allocation of attention to the receptive field reduced the population coupling strength. Attentional modulation of neurons was positively correlated with population coupling strength. While neurons on average retained their coupling strengths across conditions, some neurons change coupling strength condition dependent, thereby potentially enhancing the coding abilities of cortical circuits.

neuroscience↗

bioRxiv2020

Directed information exchange between cortical layers in macaque V1 and V4 and its modulation by selective attention

Achieving behavioral goals requires integration of sensory and cognitive information, across cortical laminae and cortical regions. How this computation is performed remains unknown. Using local field potential recordings and spectrally resolved conditional Granger causality (cGC) analysis, we mapped visual information flow, and its attentional modulation, between cortical layers within and between macaque areas V1 and V4. Stimulus induced inter-laminar information flow within V1 dominated upwardly, channeling information towards supragranular cortico-cortical output layers. Within V4, information flow dominated from granular to supragranular layers, but interactions between supragranular and infragranular layers dominated downwardly. Low-frequency across-area communication was stronger from V4 to V1, with little layer specificity. Gamma-band communication was stronger in the feedforward V1 to V4 direction. Attention to the receptive field of V1 decreased communication between all V1 layers, except for granular to supragranular layers interactions. Communication within V4, and from V1 to V4, increased with attention across all frequencies. While communication from V4 to V1 was stronger in lower frequency bands (4-25 Hz), attention modulated cGCs from V4 to V1 across all investigated frequencies. Our data show that top down cognitive processes result in reduced communication within cortical areas, increased feedforward communication across all frequency bands and increased gamma band feedback communication.

neuroscience↗

bioRxiv2020

Top-down coordination of local cortical state during selective attention

Spontaneous fluctuations in cortical excitability influence sensory processing and behavior. These fluctuations, long known to reflect global changes in cortical state, were recently found to be modulated locally within a retinotopic map during spatially selective attention. We found that periods of vigorous (On) and faint (Off) spiking activity, the signature of cortical state fluctuations, were coordinated across brain areas along the visual hierarchy and tightly coupled to their retinotopic alignment. During top-down attention, this interareal coordination was enhanced and progressed along the reverse cortical hierarchy. The extent of local state coordination between areas was predictive of behavioral performance. Our results show that cortical state dynamics are shared across brain regions, modulated by cognitive demands and relevant for behavior. One Sentence SummaryInterareal coordination of local cortical state is retinotopically precise and progresses in a reverse hierarchical manner during selective attention.

neuroscience↗

bioRxiv2018

Comprehensive profiling of the fission yeast transcription start site activity during stress and media response

Fission yeast, Schizosaccharomyces pombe, is an attractive model organism for transcriptional and chromatin biology research. Such research is contingent on accurate annotation of transcription start sites (TSSs). However, comprehensive genome-wide maps of TSSs and their usage across commonly applied laboratory conditions and treatments for S. pombe are lacking. To this end, we profiled TSS activity genome-wide in S. pombe cultures exposed to heat shock, nitrogen starvation, hydrogen peroxide and two commonly applied media, YES and EMM2, using Cap Analysis of Gene Expression (CAGE). CAGE-based annotation of TSSs is substantially more accurate than existing PomBase annotation; on average, CAGE TSSs fall 50-75 bp downstream of PomBase TSSs and co-localize with nucleosome boundaries. In contrast to higher eukaryotes, S. pombe does not show sharp and dispersed TSS distributions. Our data recapitulate known S. pombe stress expression response patterns and identify stress- and mediaresponsive alternative TSSs. Notably, alteration of growth medium induces changes of similar magnitude as some stressors. We show a link between nucleosome occupancy and genetic variation, and that the proximal promoter region is genetically diverse between S. pombe strains. Our detailed TSS map constitute a central resource for S. pombe gene regulation research.

genomics↗

bioRxiv2018

De novo origin of multicellularity in response to predation

The transition from unicellular to multicellular life was one of a few major events in the history of life that created new opportunities for more complex biological systems to evolve. Predation is hypothesized as one selective pressure that may have driven the evolution of multicellularity. Here we show that de novo origins of simple multicellularity can evolve in response to predation. We subjected outcrossed populations of the unicellular green alga Chlamydomonas reinhardtii to selection by the filter-feeding predator Paramecium tetraurelia. Two of five experimental populations evolved multicellular structures not observed in unselected control populations within ~750 asexual generations. Considerable variation exists in the evolved multicellular life cycles, with both cell number and propagule size varying among isolates. Survival assays show that evolved multicellular traits provide effective protection against predation. These results support the hypothesis that selection imposed by predators may have played a role in some origins of multicellularity.

evolutionary biology↗

bioRxiv2017

Motility in multicellular Chlamydomonas reinhardtii

The advent of multicellularity was a watershed event in the history of life, yet the transition from unicellularity to multicellularity is not well understood. Multicellularity opens up opportunities for innovations in intercellular communication, cooperation, and specialization, which can provide selective advantages under certain ecological conditions. The unicellular alga Chlamydomonas reinhardtii has never had a multicellular ancestor yet it is closely related to the volvocine algae, a clade containing taxa that range from simple unicells to large, specialized multicellular colonies. Simple multicellular structures have been observed to evolve in C. reinhardtii in response to predation or to settling rate-based selection. Structures formed in response to predation consist of individual cells grouped within a shared transparent extracellular matrix. Evolved isolates form such structures obligately under culture conditions in which their wild type ancestors do not, indicating that newly-evolved multicellularity is heritable. C. reinhardtii is capable of photosynthesis, and possesses an eyespot and two flagella with which it moves towards or away from light in order to optimize input of radiant energy. Motility contributes to C. reinhardtii fitness because it allows cells or colonies to achieve this optimum. Utilizing phototaxis to assay motility, we determined that newly evolved multicellular strains do not exhibit significant directional movement, even though the flagellae of their constituent unicells are present and active. In C. reinhardtii the first steps towards multicellularity in response to predation appear to result in a trade-off between motility and differential survivorship, a trade-off that must overcome by further genetic change to ensure the long-term success of the new multicellular organism.

evolutionary biology↗

bioRxiv2016

Multi-omic analysis of urothelial cancer patients treated with PD-L1 blockade demonstrates the contribution of both systemic and somatic factors to the biology of response and resistance

BackgroundInhibition of programmed death-ligand one (PD-L1) with atezolizumab can induce durable clinical benefit (DCB) in patients with metastatic urothelial cancers, including complete remissions in patients with chemotherapy refractory disease. Although mutation load and PD-L1 immune cell (IC) staining have been associated with response, they lack sufficient sensitivity and specificity for clinical use. Thus, there is a need to evaluate the peripheral blood immune environment and to conduct detailed analyses of mutation load, predicted neoantigens and immune cellular infiltration in tumors to enhance our understanding of the biologic underpinnings of response and resistance.\n\nMethods and FindingsThe goals of this study were to (1) evaluate the association of mutation load and predicted neoantigen load with therapeutic benefit, and (2) determine whether intratumoral and peripheral blood T cell receptor (TCR) clonality inform clinical outcomes in urothelial carcinoma treated with atezolizumab. We hypothesized that an elevated mutation load in combination with T cell clonal dominance among intratumoral lymphocytes prior to treatment or among peripheral T cells after treatment would be associated with effective tumor control upon treatment with anti-PD-L1 therapy. We performed whole exome sequencing (WES), RNA sequencing (RNA-seq), and T cell receptor sequencing (TCR-seq) of pre-treatment tumor samples as well as TCR sequencing of matched, serially collected peripheral blood collected before and after treatment with atezolizumab. These parameters were assessed for correlation with DCB (defined as progression free survival (PFS) > 6 months), PFS, and overall survival (OS), both alone and in the context of clinical and intratumoral parameters known to be predictive of survival in this disease state.\n\nPatients with DCB displayed a higher proportion of tumor infiltrating T lymphocytes (TIL) (n=24, Mann-Whitney p=0.047). Pre-treatment peripheral blood TCR clonality below the median was associated with improved PFS (n=29, log-rank p=0.048) and OS (n=29, log-rank p=0.011). Patients with DCB also demonstrated more substantial expansion of tumor-associated TCR clones in the peripheral blood 3 weeks after starting treatment (n=22, Mann-Whitney p=0.022). The combination of high pre-treatment peripheral blood TCR clonality with elevated PD-L1 IC staining in tumor tissue was strongly associated with poor clinical outcomes (n=10, HR (mean)=89.88, HR (median)=23.41, 95% CI (2.43, 506.94), p(HR>1)=0.0014). Marked variations in mutation loads were seen with different somatic variant calling methodologies, which in turn impacted associations with clinical outcomes. Missense mutation load, predicted neoantigen load and expressed neoantigen load did not demonstrate significant association with DCB (n=25, Mann-Whitney p=0.22, n=25, Mann-Whitney p=0.55, and n=25, Mann-Whitney p=0.29 respectively). Instead, we found evidence of time-varying effects of somatic mutation load on progression-free survival in this cohort (n=25, p=0.044). A limitation of our study is its small sample size (n=29), a subset of the patients treated on IMvigor 210 (NCT02108652). Given the number of exploratory analyses performed, we intend for these results to be hypothesis-generating.\n\nConclusionsThese results demonstrate the complex nature of immune response to checkpoint blockade and the compelling need for greater interrogation and data integration of both host and tumor factors. Incorporating these variables in prospective studies will facilitate identification and treatment of resistant patients.

cancer biology↗