Biology subjects

Lopez, A. F.

Publications and source records attributed to Lopez, A. F..

4 recordsLinked to original sources

bioRxiv2026

Monitoring Autonomic Tone During Spinal Cord Neuromodulation Using Wearble AURIS Sensor

The transition of bioelectronic medicine to clinical use is currently limited by a lack of non-invasive sensors capable of measuring autonomic tone during active neuromodulation. Conventional monitoring modalities, such as mean arterial pressure (MAP) and Ag/AgCl chest electrodes, are often invasive, cumbersome, or susceptible to motion artifacts. Here, we present a novel framework employing an in-ear sensor (AURIS) to continuously monitor heart rate variability (HRV) during therapeutic neuromodulation. These sensors utilize a polydimethylsiloxane (PDMS) substrate to ensure biocompatibility and superior conformability. Experiments in a rodent model (n = 3) demonstrate that the AURIS platform achieves gold-standard fidelity, with mean heart rate differences of 6.03 BPM and mean RR interval deltas of 3.18 ms compared to chest electrodes. Sensor agreement was statistically validated using independent t-tests, showing no significant difference between modalities (all p > 0.46). While time-domain shifts trended toward significance, complexity metrics showed robust sequential responses with large effect sizes, including the SD1/SD2 ratio (d = 1.474) and the DFA ratio (d = 1.091). These findings validate a sensor architecture that is durable, accessible, and provides the necessary technical foundation for closed-loop feedback and non-invasive clinical trials.

bioengineering↗

bioRxiv2025

Geometric Tuning of Cytokine Receptor Association Modulates Synthetic Agonist Signaling

Cytokines signal by bringing receptor subunits together, but the role of receptor geometry in shaping signaling remains unclear because natural ligands enforce fixed assemblies. Here, we present a de novo protein design platform that rigidly scaffolds receptor-binding domains into defined spatial arrangements. Applying this across IL-7, type I and III interferons, IL-10, gp130, {beta} common, and synthetic receptor pairs, we show that by varying geometry, we can bias pSTAT pathway usage and tune functional outcomes. Geometric control allowed us to decouple pSTAT1 from pSTAT5 in IL-7, separate antigen presentation (MHC-I) from checkpoint induction (PD-L1) in type I interferons, and suppress pro-inflammatory IFN{gamma} secretion while retaining anti-inflammatory activity in IL-10. We further created minimal IL-6 and IL-3 agonists and strengthened synthetic receptor pairings inaccessible with present cytokines. These results establish receptor geometry as a central determinant of cytokine activity and provide a platform for programmable immune modulation.

synthetic biology↗

bioRxiv2021

14-3-3ζ-depletion impairs mammary gland development in the mouse

The 14-3-3 family of proteins have roles in regulating several key cellular processes. While their significant structural and functional homology had informed the idea that these proteins acted redundantly, it is now becoming clear that individual family members may have tissue and context specific functions, highlighting the need for a more nuanced understanding of these important proteins. Here, we demonstrate that mice deficient in 14-3-3{zeta} exhibit developmental defects of the mammary epithelium, associated with dysregulation of key transcription factors involved in the maintenance of mammary stem cell populations. We believe that this model will be prove useful for investigating the role of 14-3-3{zeta} in the maintenance of mammary stem cell populations and elucidating the transcriptional networks driving specification of the mammary epithelium.

cell biology↗

bioRxiv2019

14-3-3ζ over-expression improves tolerance to acute and chronic cold exposure in male mice via thermogenic-dependent and -independent mechanisms

Following prolonged cold exposure, adaptive thermogenic pathways are activated to maintain homeothermy, and elevations in body temperature are generally associated with UCP1-dependent and -independent increases in energy expenditure. One of the earliest, identified functions of the molecular scaffold, 14-3-3{zeta}, was its role in the synthesis of norepinephrine, a key endogenous factor that stimulates thermogenesis. This suggests that 14-3-3{zeta} may have critical roles in cold-induced thermogenesis. Herein, we report that transgenic over-expression of TAP-14-3-3{zeta} in mice significantly improved tolerance to prolonged cold. When compared to wildtype controls, TAP mice displayed significantly elevated body temperatures and paradoxical decreases in energy expenditure. No changes in {beta}-adrenergic sensitivity or oxidative metabolism were observed; instead, 14-3-3{zeta} over-expression significantly decreased thermal conductance via increased peripheral vasoconstriction. These findings suggest 14-3-3{zeta} mediates alternative, non-thermogenic mechanisms to mitigate heat loss for homeothermy. Our results point to an unexpected role of 14-3-3{zeta} in the regulation of body temperature. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=137 HEIGHT=200 SRC="FIGDIR/small/853184v2_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@1f5b454org.highwire.dtl.DTLVardef@1219a7org.highwire.dtl.DTLVardef@523fb3org.highwire.dtl.DTLVardef@1d41780_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗