Biology subjects

Harmon, E.

Publications and source records attributed to Harmon, E..

4 recordsLinked to original sources

bioRxiv2026

Perivascular fibroblasts locally regulate the vasomotor dynamics of pial arterioles

Perivascular fibroblasts (PVFs) ensheath pial arterioles on the brain surface, yet their physiological role on the healthy cerebrovasculature remains unknown. Here, we show that PVFs display calcium dynamics that are temporally aligned with arteriolar vasomotion. Depletion of fibroblasts disrupted vasomotion whereas enhancement of PVF-Gq signaling increased vasomotor activity and accelerated fluid influx into the peri-arteriolar space. These findings identify PVFs as unrecognized regulators of cerebral vasodynamics and cerebrospinal fluid movement.

neuroscience↗

bioRxiv2026

Structural analyses of Trichomonas vaginalis pyrophosphate-dependent phosphofructokinase (TvPPi-PFK)

Trichomonas vaginalis causes trichomoniasis, the most common non-viral sexually transmitted disease in humans. T. vaginalis pyrophosphate-dependent phosphofructokinase (TvPPi-PFK) is a putative target for rational, structure-based drug discovery, given its absence in mammals and its importance for parasite survival. TvPPi-PFK is a cytosolic enzyme that catalyzes the phosphorylation of fructose-6-phosphate using pyrophosphate (PPi) as the phosphoryl donor. This reversible reaction, catalyzed by TvPPi-PFK, is the first committed step in glycolysis. Its reverse reaction is vital for gluconeogenesis in T. vaginalis. The purification, crystallization, structure determination, and crystal structures of TvPPi-PFK are reported. TvPPi-PFK is the first reported eukaryotic PPi-PFK structure. TvPPi-PFK retains the overall PPi-PFK topology observed in bacterial PPi-PFK including conserved motifs essential for pyrophosphate binding and PPi-PFK catalytic activity. In addition to the catalytic PPi-PFK binding sites, TvPPi-PFK has two additional ligand binding sites. The first binds AMP usurped during protein production and helps stabilize the TvPPi-PFK tetramer. A second ligand binding site was observed in proximity to the AMP-binding site and accommodates sugar phosphates soaked into preformed crystals. This sugar phosphates binding site is distinct from the TvPPi-PFK active site that binds fructose-6-phosphate. Future mutagenesis and activity studies are planned to determine the relevance of both sites. SynopsisThe production, crystallization, and crystal structures of a pyrophosphate-dependent phosphofructokinase from Trichomonas vaginalis (TvPPi-PFK) are reported. TvPPi-PFK has a prototypical PPi-PFK active site as well as unexpected AMP and sugar-phosphate binding sites at the dimer interface.

biochemistry↗

bioRxiv2026

Novel neonatal hypoxic-ischemic model demonstrates neuroinflammation-associated memory deficits without neuronal loss

BackgroundNeonatal global hypoxic-ischemic cerebral injury is a leading cause of infant mortality and lifelong disability. Current rodent models do not replicate neonatal global cerebral ischemia (nGCI) and reperfusion injury. Here, we developed and characterized a rodent model of cardiac arrest and cardiopulmonary reperfusion (CA/CPR) to induce nGCI, producing acute systemic ischemia, mild neuronal injury, white matter alterations, and motor and memory deficits. MethodsRat pups underwent CA/CPR or sham procedure on postnatal day 9-11. CA/CPR in rat pups was performed under anesthesia while intubated. Asystole was induced with intravenous (IV) KCl and maintained for 10-14 minutes. Resuscitation included oxygen ventilation, chest compressions, and IV epinephrine. ResultsTwelve minutes of asystole provided an optimal balance between survival and systemic injury. Behavioral testing on postoperative day (POD) 7 revealed memory impairments. Despite the absence of overt neuronal death in the hippocampus or cerebellum, we observed evidence of glial activation and white matter alterations. ConclusionThis novel rodent model of nGCI addresses limitations in existing models while offering clinically relevant features to support future mechanistic and translational research. ImpactO_LIThis study validates cardiac arrest and cardiopulmonary resuscitation (CA/CPR) as a novel model for neonatal global cerebral ischemia (nGCI), complementing existing rodent models of unilateral and permanent injury by enabling investigation of both global ischemia and reperfusion injury. C_LIO_LInGCI results in memory impairment in the absence of overt neuronal cell death. Functional deficits are associated with neuroinflammatory responses in the hippocampus, white matter, and cerebellum. C_LIO_LINeonatal CA/CPR induces global cerebral ischemia which uniquely allows investigation of hindbrain structures, such as cerebellum, which are typically spared in existing rodent models of neonatal hypoxia-ischemia. C_LI

neuroscience↗

bioRxiv2025

Consequences of cannibalism: induced defense and kin discrimination in a rotifer

Resource polyphenisms result in the production of environmentally induced morphs with differential niche use. These striking examples of phenotypic plasticity are taxonomically widespread and ecologically important. However, cannibalism is a frequent repercussion of resource polyphenisms. Despite some benefits, cannibalism is always costly to victims and sometimes costly to the cannibal. Therefore, we here evaluate how morphological and behavioral plastic strategies to minimize these costs may evolve. To better understand the evolution and consequences of cannibalistic polyphenisms, we tested whether rotifers Asplanchna brightwellii possess effective morphological defenses against cannibalism and the ability to discriminate by genetic relationship. We found that small humps produced by vulnerable A. brightwellii limit cannibalism. We also found that cannibals were less likely to attack clonemates than non-kin. The rotifer genus Asplanchna comprises species with varying degrees of resource polyphenism, cannibalism, induced morphological defenses, and behavioral kin discrimination. The observed induced defense and kin discrimination in Asplanchna brightwellii likely represent evolutionary intermediates facilitating the evolution of a unique trimorphic resource polyphenism in congeners.

evolutionary biology↗