Biology subjects

Sandoval, L.

Publications and source records attributed to Sandoval, L..

7 recordsLinked to original sources

bioRxiv2026

Consistency and individual variation in common song types of an urban bird: a multi-population comparison over a decade

Individual variation in singing behavior is influenced by cultural evolution, environmental constraints, and population dynamics. In closed-ended songbird species, aging may be associated to temporal song variations in individual birds due to vocal apparatus deterioration. However, song variations may also arise as a result of extrinsic factors that induce behavioral changes. In this study, we aimed to examine song-type consistency over 13 years in four populations of the White-eared Ground-sparrow (Melozone leucotis, Aves: Passerellidae) along an urban-rural gradient. We also compared within and between-individual variation to determine potential population-level responses. We used long-term data from singing males to quantify five fine structural characteristics (minimum frequency and maximum frequencies, bandwidth, peak frequency, and song duration) for two most common song types from each population. Song consistency differed between fine-structure characteristics, song types, and populations. Contrary to our expectations, we found that the Highly urbanized population had greater between-individual variance, associated with anthropogenic disturbances such as habitat structure and noise pollution, suggesting non-uniform individual responses. The Medium, Low urbanized, and Rural populations, on the other hand, had higher levels of within-individual variance, associated to individuals' age. Our study brings insight into how both intrinsic and extrinsic factors can influence song consistency and highlights how cultural evolution within a species can diverge across populations experiencing distinct environmental contexts.

animal behavior and cognition↗

bioRxiv2025

Virus-like particles enable targeted gene engineering and pooled CRISPR screening in primary human myeloid cells

Primary human myeloid cells are promising candidates for immunotherapy, yet efficient and scalable technologies for genetic engineering and screening in these cells are limited. Here we present a virus-like particle (VLP)-based toolkit that delivers diverse CRISPR genome editing modalities to human monocytes, macrophages, and dendritic cells with high efficiency while preserving viability and innate immune responsiveness. VLP-mediated delivery of ribonucleoprotein payloads supports gene knockout, base editing and epigenetic silencing, and enables site-specific integration of large DNA sequences when combined with AAV donors for homology-directed repair. Leveraging sgRNA delivery via VPX-lentivirus combined with Cas9 protein delivery via engineered virus-like particle (eVLP) treatment ("SLICeVLP"), we performed the first pooled loss-of-function screens in human macrophages. We uncovered regulators of TNF production and CD80 expression in human macrophages, converging on TNFAIP3 as a central regulator of inflammatory polarization. TNFAIP3 ablation promoted a pro-inflammatory cell state that is resistant to suppressive polarization, and augmented cytotoxicity of engineered HER2 CAR-macrophages. Taken together, this technology platform enables unbiased discovery and characterization of functional gene targets in primary human myeloid cells.

immunology↗

bioRxiv2025

Single cell resolution of an epigenetic signature of persister tumor cell

Cancer can recur when a subset of tumor cells, denoted here as persister cells, are able to survive therapy and re-enter the cell cycle. The precise mechanisms that confer the persister state and whether it is characteristic of a subgroup of cells or arises from multiple cellular lineages remain poorly understood. We hypothesize that an epigenetic signature underlies the drug-tolerant persister state, characterized by transcriptional and chromatin accessibility changes that promote survival of residual cancer following chemotherapy. To identify clinically relevant features of persister cells in untreated tumors and residual disease, we performed single-cell multiomic profiling (snRNA+snATAC) on a cohort of non-malignant fallopian tube, treatment-naive, and neoadjuvant chemotherapy (NACT)-treated high-grade serous ovarian cancer (HGSOC) samples. We identified differences in gene expression and open chromatin between naive and residual patient tumors following chemotherapy. Although only a small proportion of the differentially expressed genes enriched in residual HGSOC overlapped with established gene sets for chemo-response and patient prognosis, the epigenomic analysis revealed activity of several DNA-binding factors that are both enriched upon chemotherapy and also high in resistant tumors prior to treatment. From this analysis, we identified an epigenetic signature that precedes expression and defines the persister state. This epigenetic signature also correlated with chemotherapy sensitivity and resistance using patient-derived xenograft models of HGSOC. Gene regulatory networks driven by the persister signature are involved in the activation of oncogenic pathways, including changes to the cell cycle promoting quiescence and stress response. Further study of the persister cells identified by this epigenetic signature may increase understanding of the mechanisms underlying persister cell survival and reveal new vulnerabilities that could be exploited to delay or prevent cancer recurrence.

genomics↗

bioRxiv2023

Groundwater redox dynamics across the terrestrial-aquatic interface of Lake Erie coastal ecosystems

Groundwater biogeochemistry in coastal areas is spatially and temporally dynamic because fluctuations in groundwater level may cause alternate redox between distinct hydrological conditions. Recent studies have proposed connections between biogeochemistry and large-scale hydrological processes, specifically focusing on the role of redox-active compounds in changing the oxidation state during flooding and draining events. While water saturation generally results in a shift of redox-active compounds from electron donors to acceptors, the specific mechanisms underlying the transition of groundwater between oxidizing and reducing conditions in response to water level fluctuations are uncertain. To determine the effects of groundwater levels on redox dynamics, we monitored groundwater redox potential across the terrestrial-aquatic interface in Lake Erie coastal areas throughout the high and low-water seasons. In contrast to previously observed responses to flooding in soils, our results revealed patterns of oxidizing redox potentials during high-water and reducing during low-water periods. Furthermore, short-term fluctuations in water table levels significantly impacted the redox potential of groundwater when dissolved oxygen increased, and redox dynamics displayed voltage hysteresis in most events. Based on these findings, we propose that for improved predictions of microbial functions and biogeochemical cycles, redox-informed models should incorporate the antagonistic changes in groundwater redox balance compared to soils and consider the time lags in redox fluctuations. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=92 SRC="FIGDIR/small/544684v1_figu1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@4d7a19org.highwire.dtl.DTLVardef@8b2b92org.highwire.dtl.DTLVardef@d9bc11org.highwire.dtl.DTLVardef@ca3e13_HPS_FORMAT_FIGEXP M_FIG Graphical AbstractConceptual diagram of groundwater redox fluctuations in coastal ecosystems. Large redox fluctuations are derived by dissolved oxygen inputs and smaller more frequent redox fluctuations are led by redox sensitive species leaching from topsoil. C_FIG

ecology↗

bioRxiv2021

Sonic hedgehog is basolaterally sorted from the TGN and transcytosed to the apical domain involving Dispatched-1 at Rab11-ARE

Hedgehog (Hh) secretion from apical and/or basolateral domains occurs in different epithelial cells impacting development and tissue homeostasis. Palmitoylation and cholestyrolation attach Hh proteins to membranes and Dispatched-1 (Disp-1) promotes their release. How these lipidated proteins are handled by the complex secretory and endocytic pathways of polarized epithelial cells remains unknown. We show that MDCK cells address newly synthesized sonic hedgehog (Shh) from the TGN to the basolateral cell surface and then to the apical domain through a transcytosis pathway that includes Rab11-apical recycling endosomes (Rab11-ARE). Both palmitoylation and cholestyrolation contribute to this sorting behavior, otherwise Shh lacking these lipid modifications is unpolarized. Disp-1 mediates first basolateral secretion from the TGN and then transcytosis from the Rab11-ARE. At steady state, Shh predominates apically and can be basolaterally transcytosed. This complex Shh trafficking provides several steps for regulation and variation in different epithelia, subordinating the apical to the basolateral secretion.

cell biology↗

bioRxiv2021

A burden-free gene overexpression system

Heterologous gene activation causes non-physiological burden on cellular resources that cells are unable to adjust to. Here, we introduce a feedforward controller that increases ribosome level upon activation of a gene of interest (GOI) to compensate for such a burden. The controller achieves this by activating a modified SpoT enzyme with sole hydrolysis activity, which lowers ppGpp level and thus de-represses ribosomes. Without the controller, activation of the GOI decreased growth rate by more than 50%. With the controller, we could activate the GOI to the same level without a growth rate decrease. A cell strain armed with the controller in co-culture enabled persistent population-level activation of a GOI, which could not be achieved by a strain devoid of the controller. The feedforward controller is a tunable, modular, and portable tool that for the first time allows dynamic gene activation without growth rate defects for bacterial synthetic biology applications.

synthetic biology↗

bioRxiv2020

Vulnerability of Elevation-Restricted Endemic Birds of the Cordillera de Talamanca (Costa Rica and Panama) to Climate Change

Animals endemic to tropical mountains are known to be especially vulnerable to climate change. The Cordillera de Talamanca (Costa Rica and Panama) is a geographically isolated mountain chain and global biodiversity hotspot, home to more than 50 endemic bird species. We used eBird community science observations to predict the distributions of a suite of 48 of these endemic birds in 2006-2015, and in 2070, under four climate change scenarios. Species distributions were predicted using program Maxent, incorporating elevation, satellite derived habitat data, and WorldClim climate variables. Model fit, as assessed by Area under the Receiver Operator Curve (AUC) was very high for most species, ranging from 0.877 to 0.992 (mean of 0.94). We found that most species are predicted to undergo range contractions by 2070, with a mean of 15% under modest climate change (RCP 2.6) up to a mean of 40% under more severe climate change (RCP 8.5). Most of the current ranges of these species are within existing protected areas (average of 59% in 2006-2015), and with prospective range contractions, the importance of these protected areas is forecast to increase. We suggest that these predicted range declines should elevate conservation concerns for this suite of species, and vigilance, in the form of better population monitoring, is urgently needed.

ecology↗