Biology subjects

Stephens, H.

Publications and source records attributed to Stephens, H..

3 recordsLinked to original sources

bioRxiv2026

Presynaptic Terminals Dynamically Modulate Spontaneous Release Frequency During Early Synaptic Plasticity Through and Entropic Force Framework

Spontaneous synaptic transmission has been established as essential for the maintenance of synaptic weights during action potential-induced transmission. However, spontaneous transmission also changes during synaptic plasticity and has been shown to, in part, mediate changes in synaptic weights. Despite decades of research, a coherent framework for understanding the complex molecular processes that support presynaptic spontaneous transmission during maintenance and plasticity has remained elusive. We show here that presynapses modulate spontaneous transmission frequency during the early time-course of plasticity following entropic force theory. We use live primary hippocampal cultures as a model system and induce plasticity using an established Long-Term Potentiation (LTP) protocol. We then use a combination of electron microscopy, fluorescence microscopy, and computational modeling to show how spontaneous release frequency dynamically changes during early plasticity. We use our entropic force theory to show how the dynamically changing synaptic vesicle pool structure mediates spontaneous release changes. Lastly, we show how these changes are altered in the presence of P301L tau leading to degeneration. The results from this study provide new insights that not only help understand normal synaptic function but also aid in understanding neurodegeneration.

neuroscience↗

bioRxiv2026

Early Tracheal and Salivary miRNAs in Extremely Preterm Infants Predict BPD-related Pulmonary Hypertension

Pulmonary hypertension (BPD-PH) associated with bronchopulmonary dysplasia (BPD) in preterm infants associates with high morbidity and mortality within the first two years of life. In a previous unbiased study, we identified a panel miRNAs in tracheal aspirates (TA) that were differentially expressed in extremely low gestational age newborns (ELGANs) with BPD-PH compared to those with BPD but no PH. To explore the predictive potential of these miRNAs, we studied TA exosomes from 7 days old ELGANs and analysed a curated panel of 16 miRNAs through logistic regression and calculated the predictive AUROC to diagnose BPD-PH at 36 weeks PMA. AUROC of TA miRNAs was 0.76 with sensitivity and specificity of 53% and 93%, respectively. Adding sex and gestational age to the variables improved the AUROC to 0.78 with sensitivity and specificity of 61 and 87% respectively. Due to challenges of obtaining TA in non-invasively ventilated infants, we collected saliva samples from ELGANs at 7 days of age and compared the log expression of these 16 miRNAs in both biofluids and found significant correlation in their expression (pearson r=0.92, p<0.001). We calculated the predictive AUROC of the same miRNAs to diagnose BPD-PH at 36 weeks PMA. AUROC of these miRNAs in saliva was = 0.85 with sensitivity and specificity of 82% and 72%, respectively; addition of biological sex and gestational age improved AUROC to 0.86 with sensitivity and specificity of 79% and 76% respectively. Leave-one-sample-out sensitivity analysis demonstrated stable training performance with reduced performance in testing samples, supporting the need for validation in larger independent cohorts. In conclusion, early salivary miRNAs have great potential for risk stratification of ELGANs to develop BPD-PH, while also providing the opportunity to identify target molecules and mechanisms that modulate molecular function.

bioinformatics↗

bioRxiv2022

Epo-IGF1R crosstalk expands stress-specific progenitors in regenerative erythropoiesis and myeloproliferative neoplasm

We find that in regenerative erythropoiesis, the erythroid progenitor landscape is reshaped, and a previously undescribed progenitor population with CFU-E activity (stress CFU-E/sCFU-E) is markedly expanded to restore the erythron. sCFU-E are targets of erythropoietin (Epo) and sCFU-E expansion requires signaling from the Epo receptor (EpoR) cytoplasmic tyrosines. Molecularly, Epo promotes sCFU-E expansion via JAK2/STAT5-dependent expression of IRS2, thus engaging the pro-growth signaling from the IGF1 receptor (IGF1R). Inhibition of IGF1R/IRS2 signaling impairs sCFU-E cell growth, whereas exogenous IRS2 expression rescues cell growth in sCFU-E expressing truncated EpoR lacking cytoplasmic tyrosines. This sCFU-E pathway is the major pathway involved in erythrocytosis driven by the oncogenic JAK2 mutant, JAK2(V617F), in myeloproliferative neoplasm. Inability to expand sCFU-E cells by truncated EpoR protects against JAK2(V617F)-driven erythrocytosis. In myeloproliferative neoplasm patient samples, the number of sCFU-E like cells increases, and inhibition of IGR1R/IRS2 signaling blocks Epo-hypersensitive erythroid cell colony formation. In summary, we identify a new stress-specific erythroid progenitor cell population that links regenerative erythropoiesis to pathogenic erythrocytosis. Key PointsO_LIEpo-induced IRS2 allows engagement of IGF1R signaling to expand a previously unrecognized progenitor population in erythropoietic stress. C_LIO_LITruncated EpoR does not support stress CFU-E expansion and protects against JAK2(V617F)-driven erythrocytosis in MPN. C_LI

developmental biology↗