Biology subjects

Gore, A.

Publications and source records attributed to Gore, A..

5 recordsLinked to original sources

bioRxiv2025

The developing leaf of the wild grass Brachypodium distachyon at single-cell resolution

Leaves are the plants main photosynthetic organs and drive Earths primary production. Grasses form longitudinal leaves with parallel venation and graminoid stomata. Yet, how distinct leaf tissues coordinatively develop to build functional grass leaf anatomy is not well understood. Here, we decoded the developing grass leaf from vegetative meristems to mature tissues using single-cell RNA-sequencing in the wild grass Brachypodium distachyon. In-depth analysis of epidermal clusters and multiplexed whole-mount RNA-fluorescence in situ hybridization resolved most epidermal lineages and confirmed them in planta. Gene regulatory network analysis distinguished the targetome of the two co-expressed, yet functionally divergent stomatal transcription factors BdMUTE and BdFAMA. Finally, we used our dataset to identify and functionally describe BdGRAS32s role in cell division inhibition and a stomata-specific function for a cell wall modifying enzyme. Together, our single-cell grass leaf atlas enables the dissection of developmental processes that shape the leaf sustaining global food production.

plant biology↗

bioRxiv2022

Synaptic Spinules are Reliable Indicators of Excitatory Presynaptic Bouton Size and Strength in CA1 Hippocampus

Synaptic spinules are thin, finger-like projections from one neuron that become fully embedded within the presynaptic or postsynaptic compartments of another neuron. While spinules are a conserved feature of synapses across the animal kingdom, their specific function(s) remain unknown. Recent focused ion beam scanning electron microscopy (FIB-SEM) image volume analyses have demonstrated that spinules are embedded within [~] 25% of excitatory boutons in mammalian primary visual cortex, yet the diversity of spinule sizes, origins, and ultrastructural relationship to their boutons remained unclear. To begin to uncover the function of synaptic spinules, we sought to determine the abundance, origins, and 3D ultrastructure of spinules embedded within excitatory presynaptic spinule-bearing boutons (SBBs) in mammalian CA1 hippocampus and compare these boutons with presynaptic boutons bereft of spinules (non-SBBs). Accordingly, we performed a comprehensive 3D analysis of every excitatory presynaptic bouton, their embedded synaptic spinules, and postsynaptic densities, within a 5 nm isotropic FIB-SEM image volume from CA1 hippocampus of an adult male rat. Surprisingly, we found that [~]74% of excitatory presynaptic boutons in this volume contained at least one spinule, suggesting that they are fundamental components of excitatory synapses in CA1. In addition, we found that SBBs are 2.5-times larger and have 60% larger PSDs than non-SBBs. Moreover, synaptic spinules within SBBs are clearly differentiated into two groups: small clathrin-coated spinules, and 29-times larger spinules without clathrin. Together, these findings suggest that the presence of a spinule is a marker for stronger and more stable presynaptic boutons in CA1, and that synaptic spinules serve at least two separable and distinct functions.

neuroscience↗

bioRxiv2021

Long-Term Imaging of Living Adult Zebrafish

The zebrafish has become a widely used animal model due in large part to its accessibility to and usefulness for high-resolution optical imaging. Although zebrafish research has historically focused mostly on early development, in recent years the fish has increasingly been used to study regeneration, cancer metastasis, behavior, and other processes taking place in juvenile and adult animals. However, imaging of live adult zebrafish is extremely challenging, with survival of adult fish limited to a few tens of minutes using standard imaging methods developed for zebrafish embryos and larvae. Here, we describe a new method for imaging intubated adult zebrafish using a specially designed 3D printed chamber for long-term imaging of adult zebrafish on inverted microscope systems. We demonstrate the utility of this new system by nearly day-long observation of neutrophil recruitment to a wound area in living double-transgenic adult casper zebrafish with fluorescently labeled neutrophils and lymphatic vessels.

developmental biology↗

bioRxiv2017

An epigenetic mechanism for cavefish eye degeneration

Coding and non-coding mutations in DNA contribute significantly to phenotypic variability during evolution. However, less is known about the role of epigenetics in this process. Although previous studies have identified eye development genes associated with the loss of eyes phenotype in the Pachon blind cave morph of the Mexican tetra Astyanax mexicanus1-6, no inactivating mutations have been found in any of these genes2,3,7-10. Here we show that excess DNA methylation-based epigenetic silencing promotes eye degeneration in blind cave Astyanax mexicanus. By performing parallel analyses in Astyanax mexicanus cave and surface morphs and in the zebrafish Danio rerio, we have discovered that DNA methylation mediates eye-specific gene repression and globally regulates early eye development. The most significantly hypermethylated and down-regulated genes in the cave morph are also linked to human eye disorders, suggesting the function of these genes is conserved across the vertebrates. Our results show that changes in DNA methylation-based gene repression can serve as an important molecular mechanism generating phenotypic diversity during development and evolution.

evolutionary biology↗

bioRxiv2017

Model Based Safety Ranking Of Opioid Drugs Using Adversity Index

Annual ADR report counts of opioid drugs are examined to develop a candidate index of overall safety of a drug. Actual counts for various drugs have been sourced from www.vigiaccess.org. A feature found to be common to all drugs considered is that an exponential function adequately describes the pattern of cumulative counts. In the exponential model, the parameter in the exponent (rate constant) is robust and remains the same whether counts are corrected for exposure or not. We propose use of this rate constant as adversity index of a drug. Drugs in use can be ranked by value of adversity index, lower value suggesting safer drug.\n\nKey pointsCumulative total of annual ADR report counts of opioid drugs follows an exponential pattern. Rate constant in the model is independent of volume of use of the drug. Hence it is a suitable index of overall safety.

pharmacology and toxicology↗