Biology subjects

Palmer, C. M.

Publications and source records attributed to Palmer, C. M..

6 recordsLinked to original sources

bioRxiv2026

Decoding the role of microbial interspecies interactions on nitrogen fixation

Nitrogen fixation performed by rhizosphere bacteria has the potential to improve the sustainability of cereal crop cultivation. Deciphering the role of interspecies interactions on nitrogen fixation is crucial for devising strategies to enhance this process. To unravel the contributions of interspecies interactions, we constructed synthetic microbial communities from the bottom-up that contain diazotrophic bacteria that fix nitrogen and maize rhizosphere bacteria that do not have this capability. Interactions that impacted nitrogenase activity via growth-independent mechanisms were prevalent in the system. Nitrogenase activity increased and eventually saturated as a function of the number of inoculated diazotrophs. Using a tailored machine learning model for microbiome dynamics and explainable artificial intelligence, we deciphered species contributions on nitrogenase activity and diazotroph growth. We identified a community containing Klebsiella variicola, Herbaspirillum seropedicae, and Stutzerimonas stutzeri as a starting point for developing microbial inoculants for cereal crops. Taken together, these results provide insights into the role of interspecies interactions on nitrogenase activity.

systems biology↗

bioRxiv2026

Acute Ethanol Exposure Induces Stage-Specific Bioenergetic, Mitochondrial and Neurodevelopmental Transcriptional Remodeling in Human Forebrain Progenitors

Prenatal alcohol exposure (PAE) is associated with long-term neurodevelopmental risk, yet how neuronal progenitor metabolism responds to alcohol across developmental stages remains unclear. Here, we integrated brain-isoform-focused analysis of public datasets with targeted transcriptional, translational, and functional mitochondrial assessments in human iPSC-derived cortical progenitor models representing distinct bioenergetic states. Re-analysis of prior PAE studies revealed broad metabolic gene downregulation in embryonic systems, whereas neurodevelopmental models showed limited and non-coherent transcriptional signatures. In vitro, acute ethanol exposure (AEE) induced stage-dependent transcriptional remodeling in iPSC-derived neuronal progenitor cells. Early progenitors exhibited selective upregulation of mitochondrial-associated transcripts alongside increased neuronal lineage markers. In contrast, late progenitors showed broader increases in glycolytic, lipid, and mitochondrial gene expression. Despite these transcriptional changes, mitochondrial ATP production and mitochondrial protein abundance remained unchanged in both models with altered dynamics being restricted to late progenitors. These findings indicate that ethanol exposure is associated with developmental stage-dependent neuronal remodeling of bioenergetic genes. Measurements of mitochondrial-neural frameworks after AEE showed no major alterations in either model. Overall, our results reveal a dissociation between transcriptional, translational, and functional bioenergetic outputs in models of early human neurodevelopment and highlight that transcriptional alterations of mitochondria and cellular bioenergetics under AEE should be interpreted in the context of developmental stage rather than in isolation as evidence of energetic dysfunction.

neuroscience↗

bioRxiv2026

Developmental Bioenergetic Reprogramming and Glycolytic Shift in Schizophrenia Vulnerability

Schizophrenia (SZ) arises from complex gene-environment interactions, yet how early insults shape later circuit vulnerability remains unclear. Here, we investigated whether bioenergetic states represent a convergent disease signature across genetic and environmental risk factors. We analyzed transcriptional profiles across neocortical development in murine models of maternal immune activation (polyIC MIA), and serine racemase deletion (Srr-/-), extending these analyses to juvenile stages in Srr-/- and interneuron-specific NMDA receptor deletion (Nkx2.1:Grin1fl/fl), highlighting cell-type-specific metabolic vulnerability across developmental stages. In MIA, early gestation (E12.5) revealed a transient bioenergetic shift likely driven by microglial and radial glial populations, suggesting metabolic priming rather than canonical inflammatory signaling. By late gestation (E17.5), MIA induced coordinated dysregulation of neuronal glycolytic isoforms alongside mitochondrial and lipid-associated metabolic pathways, suggesting coordinated metabolic remodeling involving lipid-linked processes. In contrast, Srr-/- mice showed minimal glycolytic alterations at E17.5, indicating that isolated genetic perturbation is insufficient to recapitulate this fetal metabolic state. However, at juvenile stages, region-specific bioenergetic adaptations emerged. Srr-/- mice exhibited global cortical increases in glycolytic gene expression, with hippocampal changes potentially enriched in neuronal populations. Conversely, Nkx2.1:Grin1fl/flinterneurons showed increased glycolytic and TCA cycle transcription in the hippocampus but opposing patterns in the medial prefrontal cortex. Together, these findings identify increased glycolytic activity, potentially linked to lactate metabolism, as a partially convergent developmental mechanism bridging prenatal perturbations and later circuit dysfunction in SZ, and suggest that downstream glycolysis-linked pathways may contribute to phenotypic heterogeneity. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=174 SRC="FIGDIR/small/723970v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@1dd1461org.highwire.dtl.DTLVardef@1651b65org.highwire.dtl.DTLVardef@e98bc8org.highwire.dtl.DTLVardef@d813a2_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2025

Uncovering synaptic and cellular nanoarchitecture of brain tissue via seamless in situ trimming and milling for cryo-electron tomography

Cell-cell communication underlies all emergent properties of the brain, including cognition, learning and memory. The physical basis for these communications is the synapse, a multi-component structure requiring coordinated interactions between diverse cell types. However, many aspects of three-dimensional (3D) synaptic organization remain poorly understood. Here, we developed an approach, seamless in situ trimming and milling (SISTM), to reliably fabricate sufficiently thin lamellae for mapping of the 3D nanoarchitecture of synapses in mouse, monkey and human brain tissue under near-native conditions via cryo-electron tomography (cryo-ET). We validated SISTM in a mouse model of Huntingtons disease, demonstrating distinct 3D alterations to synaptic vesicles and mitochondria. By successfully applying SISTM to macaque brain, we described the 3D architecture of a tripartite synapse within the cortex. Subtomogram averaging (STA) enabled spatial mapping of astrocyte-neuron contacts within the tripartite synapse, revealing neurexin-neuroligin complexes as potential constituents that tether the two cell types. Finally, we showed that the defining features of synaptic nanoarchitecture were conserved across species and evident in human brain tissue obtained postmortem. Combining SISTM with cryo-ET and STA is a starting point for a new understanding of brain organization, disease-induced structural alterations and the development of rational, structure-guided therapeutics.

cell biology↗

bioRxiv2021

Cryo-EM single particle structure refinement and map calculation using Servalcat

In 2020, cryo-EM single particle analysis achieved true atomic resolution, thanks to technological developments in hardware and software. The number of high resolution reconstructions continues to grow, increasing the importance of accurate determination of atomic coordinates. Here, a new Python package and program called Servalcat is presented that is designed to facilitate atomic model refinement. Servalcat implements a refinement pipeline, using the program REFMAC5 from the CCP4 package. After the refinement, Servalcat calculates a weighted Fo - Fc difference map, which was derived from Bayesian statistics. This map helps manual and automatic model building in real space, as is common practice in crystallography. The Fo - Fc map helps visualisation of weak features including hydrogen densities. Although hydrogen densities are weak, they are stronger than in electron density maps produced by X-ray crystallography, and some hydrogen atoms are even visible at [~] 1.8 [A] resolution. Servalcat also facilitates atomic model refinement under symmetry constraints. If a point group symmetry has been applied to the map during reconstruction, the asymmetric unit model is refined with appropriate symmetry constraints.

biophysics↗

bioRxiv2019

Mitigating Local Over-fitting During Single Particle Reconstruction with SIDESPLITTER

Single particle analysis of cryo-EM images enables macromolecular structure determination at resolutions approaching the atomic scale. Experimental images are extremely noisy, however, and during iterative refinement it is possible to stably incorporate noise into the reconstructed density. Such "over-fitting" can lead to misinterpretation of the structure, and thereby flawed biological results. Several strategies are routinely used to prevent the spurious incorporation of noise within reconstructed volumes, the most common being independent refinement of two sides of a split dataset. In this study, we show that over-fitting remains an issue within regions of low local signal-to-noise in reconstructed volumes refined using the half-set strategy. We propose a modified filtering process during refinement through the application of a local signal-to-noise filter, SIDESPLITTER, which we show to be capable of reducing over-fitting in both idealised and experimental settings, while maintaining independence between the two sides of a split refinement. SIDESPLITTER can also improve the final resolution in refinements of structures prone to severe over-fitting, such as membrane proteins in detergent micelles.

biophysics↗