Biology subjects

Manicka, S.

Publications and source records attributed to Manicka, S..

4 recordsLinked to original sources

bioRxiv2026

A topoietic model of collective morphogenesis and compartmentalization

Xenopus laevis embryos survive teratogenic stress at significantly higher rates in larger groups, a phenomenon termed cross-embryo morphogenetic assistance (CEMA) (Tung, Sperry et al. 2024). We introduce topoiesis, a proposed mechanism by which a constitutively secreted stress signal (extracellular ATP or adenosine) diffuses and decays across the group, accumulating more in larger groups where interior volume outpaces absorbing surface. We find that this rising field carries more embryos to survival and demarcates the collective more sharply from its surroundings as collective screening strength grows with size. At intermediate sizes the outcome is spatially organized (a rescued interior enclosed by a failing periphery) and reconstitutes after shuffling. In larger groups the field restructures: its peak concentration keeps rising while its interior gradient flattens into a near-uniform bulk bounded by a sharp rim, sharpening demarcation while blurring distinctions among interior members. This pre-pattern stabilizes well before individual fate commitment, opening a window in which collective geometry can act on survival outcome. A biophysically calibrated minimal model capturing these principles recapitulates CEMA rescue rates across all six observed group sizes (N=1-306; 0%-92%) and the size-dependent craniofacial defect rate among survivors. It predicts that sealing a group's boundary against loss, rather than changing its size or biochemical regulation, moves mean rescue from 0% to 100% and reorganizes the rescue structure, tracking the predicted field geometry. These results reveal a hidden simplicity behind apparent complexity: diffusion and geometry alone may suffice to make a collective both spatially organized and controllable through macroscale intervention rather than microscale engineering of its members.

biophysics↗

bioRxiv2025

Persistent Cognitive Impairment and Bone Health Following Helium (4He) Ion Exposure: Implications for Space Travel

The current study investigated the long-term neurobehavioral and physiological effects of low-dose helium (4He; 250 MeV/n) ion exposure, a significant component of galactic cosmic radiation (GCR), on male Long Evans rats. Groups of rats were trained on the rodent psychomotor vigilance test (rPVT) and irradiated at the NASA Space Radiation Laboratory at Brookhaven National Laboratory. Following exposure, they were tested in the rPVT from 30 - 180 days, and assessed for social recognition memory at 30, 90, and 180 days. At each time point, blood and bone samples were collected for subsequent analysis. We found that acute exposure to 4He ions (25 cGy) significantly impaired sustained attention, resulting in increased lapses in attention, increased reaction time measures, and decreased correct responses. However, exposure to 5 cGy 4He ions only increased some reaction time measures in the rPVT. Both groups displayed impaired social recognition memory. When deficits were found, they persisted for 180 days post-exposure, showing no signs of recovery. Notably, impairments in sustained attention appeared to worsen over time. While these low exposure doses of 4He did not significantly alter overall bone mechanical properties, specific individual parameters of bone strength were affected, and age-related changes likely played a role in observed skeletal integrity changes. Furthermore, we identified significant correlations between circulating cytokines (TNF-, IL-1{beta}), undercarboxylated osteocalcin (ucOC) levels, and bone biomechanical properties with behavioral performances. These findings suggest the potential for these blood- and bone-based targets to serve as diagnostic biomarkers for radiation-induced neurobehavioral effects, opening avenues for future countermeasure development. The sustained and progressive nature of the neurobehavioral deficits observed underscores the critical need for effective countermeasures to protect astronaut health and performance during exploration-class missions.

animal behavior and cognition↗

bioRxiv2023

Information integration during bioelectric regulation of morphogenesis in the embryonic frog brain

Spatiotemporal bioelectric states regulate multiple aspects of embryogenesis. A key open question concerns how specific multicellular voltage potential patterns differentially activate distinct downstream genes required for organogenesis. To understand the information processing mechanisms underlying the relationship between spatial bioelectric patterns, genetics, and morphology, we focused on a specific spatiotemporal bioelectric pattern in the Xenopus ectoderm that regulates embryonic brain patterning. We used machine learning to design a minimal but scalable bioelectric-genetic dynamical network model of embryonic brain morphogenesis that qualitatively recapitulated previous experimental observations. A causal integration analysis of the model revealed a simple higher-order spatiotemporal information integration mechanism relating the spatial bioelectric and gene activity patterns, where the latter is expressed as a function of the causal influence of the voltages of groups of cells. Specific aspects of this mechanism include causal apportioning (certain cell positions are more important for collective decision making), informational asymmetry (depolarized cells are more influential than hyperpolarized cells), long distance influence (genes in a cell are variably sensitive to voltage of faraway cells), and division of labor (different genes are sensitive to different aspects of voltage pattern). The asymmetric information-processing character of the mechanism led the model to predict an unexpected degree of plasticity and robustness in the bioelectric prepattern that regulates normal embryonic brain development. Our in vivo experiments verified these predictions via molecular manipulations in Xenopus embryos. This work shows the power of using a minimal in silico approach to drastically reduce the parameter space in vivo, making hard biological questions tractable. These results provide insight into the collective decision-making process of cells in interpreting bioelectric pattens that guide large-scale morphogenesis, suggesting novel applications for biomedical interventions and new tools for synthetic bioengineering.

developmental biology↗

bioRxiv2021

Biological regulatory networks are less nonlinear than expected by chance

The extent to which the components of a biological system are (non)linearly regulated determines how amenable they are to therapy and control. To better understand this property termed regulatory nonlinearity, we analyzed a suite of 137 published Boolean network models, containing a variety of complex nonlinear regulatory interactions, using a probabilistic generalization of Boolean logic that George Boole himself had proposed. Leveraging the continuous-nature of this formulation, we used Taylor decomposition to approximate the models with various levels of regulatory nonlinearity. A comparison of the resulting series of approximations of the biological models with appropriate random ensembles revealed that biological regulation tends to be less nonlinear than expected, meaning that higher-order interactions among the regulatory inputs tend to be less pronounced. A further categorical analysis of the biological models revealed that the regulatory nonlinearity of cancer and disease networks could not only be sometimes higher than expected but also relatively more variable. We show that this variation is caused by differences in the apportioning of information among the various orders of regulatory nonlinearity. Our results suggest that there may have been a weak but discernible selection pressure for biological systems to evolve linear regulation on average, but for certain systems such as cancer, on the other hand, to also evolve more nonlinear rules.

systems biology↗